缺血后处理抗大鼠肾缺血—再灌注损伤的作用机制研究
|
摘要
[研究背景和目的]
肾脏是高灌流、对缺血-再灌注易受损伤的器官。缺血-再灌注损伤(ischemia reperfusion injury,IRI)在许多肾脏疾病,例如:肾移植、肾部分切除术、肾动脉血管成形术、动脉分流术、意外创伤、肾积水和输尿管手术过程中均会发生,是临床上导致急性肾功能衰竭的主要原因之一,死亡率较高,且存活的患者也会发生不同程度的慢性肾功能损害。因此,寻找防治肾脏缺血-再灌注损伤的方法与措施一直是近年来研究的热点的问题。
缺血预处理(ischemic preconditioning,IPreC)是目前公认的一种有效的抗器官组织缺血-再灌注损伤的机械性干预措施。1999年,Toosy等证实给予肾脏几个短暂的停灌/再灌处理,可以对后来发生的长时间的缺血损伤有比较明显的保护作用。但是,缺血预处理必须在IRI发生之前进行,这对于许多无法预期的肾脏缺血性疾病是不可能实现的,例如:在肾移植中,肾源的供给许多是无法预料的,也不可能有进行缺血预处理的时机,使缺血预处理的临床应用受到很大的限制。
缺血后处理(ischemic postconditioning,IPostC)是2003年由Vinten-Johansen's研究小组提出了一种新的机械性干预措施,即在心肌缺血发生之后,再灌注开始时给予3个短暂循环的再灌/停灌的处理。这种新的干预措施可以缩小心梗面积、保护内皮功能、减轻细胞水肿、减少缺血梗死区中性粒细胞的聚集和改善心功能,对心肌缺血-再灌注损伤有比较明显的保护作用,且作用程度与缺血预处理相似。与缺血预处理不同,缺血后处理是在组织器官缺血之后才实施,在临床上应用具有“简单、可行、有效”三大特点,目前被认为是一种防治缺血性疾病的新的机械性抗损伤措施,广泛地被应用于抗器官组织缺血-再灌注损伤的防治。
因此,本研究探讨了缺血后处理对肾脏IRI的保护作用,通过与缺血预处理相比较,从整体、细胞和分子水平上阐明缺血后处理抗大鼠肾脏IRI的作用机制,本研究可为外科抗肾脏缺血-再灌注损伤提供新的策略,也可为缺血后处理防治肾脏缺血-再灌注损伤的应用提供理论和实验依据。
[方法]
SPF级SD雄性大鼠,体重:180～220 g,随机分为①假手术组(Sham组):仅行开腹右肾切除,左肾蒂分离,不夹闭;②缺血-再灌注组(I/R组):开腹右肾切除,左肾蒂分离,无创血管夹夹闭45 min;③缺血预处理组(IPreC组):开腹右肾切除,左肾蒂分离,行3个循环夹闭2 min/再灌5 min预处理后,无创血管夹夹闭45 min;④缺血后处理组(IPostC组):开腹右肾切除,左肾蒂分离,无创血管夹夹闭45 min后,行6个循环夹闭10 sec/再灌10 sec后处理,各组再灌24 h。
本研究分两个部分:
1.缺血后处理抗大鼠肾脏缺血-再灌注损伤作用
应用分光分析法测定血清肌酐(Cr)、尿素氮(BUN)评价肾功能;HE染色观察肾组织病理形态学改变,评价缺血后处理抗大鼠肾脏缺血-再灌注损伤作用。
2.缺血后处理抗大鼠肾缺血-再灌注损伤的机制研究
分别从以下3方面进行探讨:
A从抗氧化途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制
应用分光分析法测定肾组织丙二醛(MDA)、还原性谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活性:采用Real Time RT-PCR和Western blotting法分别测定SOD mRNA和蛋白表达情况,探讨缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制。
B从抗炎途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制
应用分光分析法测定肾组织中性粒细胞髓过氧化物酶(MPO)活性,采用Real Time RT-PCR和Western blotting法分别测定环氧酶(COX-1,COX-2)mRNA和蛋白表达情况,探讨缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制。
C从抗细胞凋亡途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制
应用DNA琼脂糖凝胶电泳法和末端脱氧核苷酸转移酶介导dUTP缺口末端标记法(TUNEL法)检测大鼠肾组织细胞凋亡发生情况;采用Real TimeRT-PCR和Western blotting法分别测定Bcl-2、Bax mRNA和蛋白的表达情况,探讨缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制。
[结果]
1.缺血后处理抗大鼠肾脏缺血-再灌注损伤作用
①肾功能的评价
与Sham组比较,I/R、IPreC和IPostC组的Cr及BUN水平明显升高(P＜0.05);与I/R组比较,IPreC和IPostC组的Cr及BUN水平明显降低(P＜0.05),IPreC和IPostC组Cr及BUN水平无明显差异(P＞0.05)。
②肾组织病理学观察
Sham组肾小球、肾小管没有发现明显的形态学改变,I/R组肾小管上皮细胞肿胀,出现水样变性和空泡变性,肾小管扩张,内可见管型和坏死脱落细胞,少量管腔内有蛋白性液体积聚,部分肾小管结构毁损,间质充血水肿,大量炎性细胞浸润,管周血管明显扩张淤血;IPreC和IPostC组肾小球轻度淤血,少量肾小管上皮细胞轻度水肿,空泡变性,少见管型,间质充血水肿,有少量炎性细胞浸润,管周稍有淤血。
2.从抗氧化途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制
①各氧化指标的变化
与Sham组比较,I/R、IPreC和IPostC组的MDA浓度明显升高,GSH浓度、SOD、CAT和GSH-Px活性明显降低(P＜0.05);与I/R组比较,IPreC和IPostC组的MDA浓度明显降低,GSH水平SOD、CAT和GSH-Px活性明显升高(P＜0.05),IPreC和IPostC组各个指标水平无明显差异(P＞0.05)。
②SOD mRNA和蛋白表达
与Sham组比较,I/R、IPreC和IPostC组的SOD mRNA和蛋白表达明显下降(P＜0.05),与I/R组比较,IPreC和IPostC组的SOD mRNA和蛋白表达相对升高,IPreC和IPostC相比,SOD mRNA和蛋白表达无明显差异(P＞0.05)。
3.从抗炎途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制
①MPO活性的变化
与Sham组比较,I/R、IPreC和IPostC组的MPO活性明显升高(P＜0.05);与I/R组比较,IPreC和IPostC组的MPO活性明显降低(P＜0.05)。
②COX蛋白表达
各组COX-1 mRNA和蛋白表达无统计学差异。与Sham组比较,I/R、IPreC和IPostC组的COX-2 mRNA和蛋白表达明显升高(P＜0.05),与I/R组比较,IPreC和IPostC组COX-2的mRNA和蛋白表达明显降低(P＜0.05),IPreC和IPostC相比,COX-2的mRNA和蛋白表达无明显差异(P＞0.05)。
4.从抗细胞凋亡途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制
①肾小管上皮细胞凋亡的状况
与Sham组比较,I/R、IPreC和IPostC细胞凋亡数明显增加,凋亡指数(AI)明显增高(P＜0.05);与I/R组相比较,IPreC和IPostC细胞凋亡数明显减少,AI明显降低(P＜0.05),IPreC和IPostC组AI无明显差异(P＞0.05)。
②Bcl-2、Bax mRNA和蛋白表达
与Sham组比较,I/R、IPreC和IPostC组的Bcl-2 mRNA和蛋白表达明显下降,Bax mRNA和蛋白表达相对升高,Bcl-2/Bax下降(P＜0.05);与I/R组比较,IPreC和IPostC组的Bcl-2 mRNA和蛋白表达相对升高,Bax mRNA和蛋白表达相对降低,Bcl-2/Bax明显升高(P＜0.05),IPreC和IPostC相比,Bcl-2和Bax的mRNA和蛋白表达无明显差异(P＞0.05)。
[结论]
1.肾缺血-再灌注使大鼠肾功能和结构受损,表现为Cr和BUN升高,肾小球、肾小管受损,MDA、MPO升高,GSH、SOD、CAT和GSH-Px活性降低,SOD的mRNA和蛋白表达下降,COX-2 mRNA和蛋白表达升高,肾组织细胞凋亡增加,Bcl-2 mRNA和蛋白表达降低,Bax mRNA和蛋白表达升高。
2.缺血后处理能减轻Cr和BUN水平,减轻肾组织结构的损伤,具有显著的抗大鼠肾缺血-再灌注损伤的作用。
3.缺血后处理抗大鼠肾缺血-再灌注损伤作用机制与抗氧化有关,可能是通过清除氧自由基,抑制脂质过氧化,升高组织抗氧化物酶的活性和蛋白表达,提高肾组织的抗氧化能力。
4.缺血后处理抗大鼠肾缺血-再灌注损伤作用机制与抗炎有关,可能是通过抑制中性粒细胞聚集,抑制COX-2 mRNA和蛋白的表达,从而抑制炎症介质的产生。
5.缺血后处理抗大鼠肾缺血-再灌注损伤作用机制与抗细胞凋亡作用有关,可能是通过调控细胞凋亡相关基因Bcl-2/Bax mRNA和蛋白表达。
6.缺血后处理抗大鼠肾缺血-再灌注损伤作用及其机制与缺血预处理有相似之处。
7.缺血后处理抗大鼠肾缺血-再灌注损伤的作用及机制的研究有助于为防治肾脏缺血-再灌注损伤提供理论和实验依据,为外科抗肾脏缺血-再灌注损伤提供新的策略。
Background and objective
Kidney is easily subjected to ischemic reperfusion injury due to its abundance of blood supply. The temporary discontinuation of renal blood supply is encountered in many clinical situations, such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass, aortic bypass surgery, accidental or iatrogenic trauma, sepsis, hydronephrosis and elective urological operations. Acute renal failure (ARF) resulting from renal ischemia reperfusion injury (IRI) remains a major clinical problem because of its frequent occurrence and high mortality. How to treat the renal IRI is always keeping in attention.
Currently, ischemic preconditioning (IPreC) is a well-known method in treating organ IRI. Toosy demonstrated that several short cycles of ischemia and reperfusion before renal ischemia could effectively render the renal resistant to a subsequent ischemic insult, although extensive researches have demonstrated that IPreC reduced renal IRI. However, IPreC is clinically feasible only when the occurrence of ischemia is predictable. It is fail to treat unpredictable accident events. It is need to find out other useful method to amelioration renal IRI.
Compared to ischemia, the onset of reperfusion is more predictable. In 2003, Vinten-Johnsen and his colleagues reported that brief episodes of myocardial ischemia and reperfusion employed during reperfusion after a prolonged ischemic insult had been demonstrated to play a cardioprotective role. This phenomenon was termed "Ischemic postconditioning (IPostC)". In a dog model, IPostC limited infarct size, reduced tissue edema and poly morphonuclear neutrophil accumulation in the area at risk myocardium, and improved endothelial function. It has been suggested that IPostC is as effective as IPreC in limiting infarct size and preserving postischemic endothelial function. Numerous studies demonstrated that IPostC was a simple and harmless method which provided a new tool to protect organ from IRI.
Therefore, we investigated the protective role and mechanism of ischemic postconditioning against renal IRI in rats and compared the results with IPreC. Our study may not only provide a useful theoretical and practical evidence for reducing renal IRI, but also provide a novel approach for clinic application.
Methods
Adult male Sprague-Dawley rats (180～220 g) were randomly separated into four groups: a) Sham group: the right kidneys were removed only; b) IR group: after right nephrectomy, kidneys were subjected to 45 min of ischemia; c) IPreC group: kidneys were subjected to three cycles of 2 min ischemia separated by 5 min reperfusion periods before 45 min of ischemia; d) IPostC group: kidneys were subjected to 45 min of ischemia followed by six cycles of 10 sec reperfusion separated by 10 sec ischemia. Rats were sacrificed and kidneys were harvested after reperfusion. Each group comprised eight rats. The following two aspects were investgated.
1. The protective effects of IPostC on renal IRI in rats.
Serum Cr and BUN were evaluated by Cr assay kits and BUN assay kits at 24 h after IRI, respectively. The renal pathologic changes were observed by HE-staining at 24 h after IRI.
2. The mechanism associated with renal IRI
A The antioxidative mechanism of IPostC against renal IRI in rat
SOD, CAT, and GSH-Px activity were investigated. GSH and MDA at 1 h, 3 h, 6 h, 12 h, and 24 h were measured. The mRNA and protein expression of SODat 1 h, 6 h and 24 h were evaluated by Real Time RT-PCR and Western blotting.
B The antiinflammatory mechanism of IPostC against renal IRI in rat
MPO activity at 1 h, 3 h, 6 h, 12 h and 24 h was investigated.The mRNA andprotein expression of SOD at 1 h, 3 h, 6 h, 12 h and 24 h were evaluated by RealTime RT-PCR and Western blotting.
C The antiapoptosis mechanism of IPostC against renal IRI in rat
Apoptosis was compared by TUNEL method; Real time RT-PCR assay for theBcl-2 and Bax mRNA at 6 h was evaluated; Western blotting assay for the proteinexpression of Bcl-2 and Bax at 6 h was evaluated.
Results
1. The protective effects of IPostC on renal IRI in rats
The renal function of rats 24 h after IRI was significantly different between groups. Rats subjected to IRI showed significant increase in serum Cr and BUN compared with Sham group (P < 0.05). The renal function changes caused by IRI were significantly improved by IPreC and IPostC treatments (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
Renal IRI resulted in significant renal injury as evidenced by tubular necrosis, medullary hemorrhage, congestion, and development of proteinaceous casts. In contrast, treatments of IPreC and IPostC ameliorated these severe renal damages. According to Jablonski scores, 45 min renal ischemia followed by 24 h reperfusion resulted in severe acute tubular necrosis. Quantitative analysis showed a dramatically decreased score in both IPreC group and IPostC group compared with IRI group (P < 0.05). There were no significant difference between IPreC and IPostC (P> 0.05).
2. The antioxidative mechanism of IPostC against renal IRI in rat
Compared with Sham group, the I/R group resulted in significant down-regulation of the activities of SOD, CAT, and GSH-Px in renal at 1.5 h, 3 h, 6 h, 12 h and 24 h (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant up-regulation of their activities at each time (P < 0.05); compared with Sham group, the IRI rats resulted in significant increases of the levels of MDA, and decreases of GSH in renal tissue at 1 h, 3 h, 6 h, 12 h and 24 h. While compared with I/R group, IPreC and IPostC treatments resulted in significant decreases of the levels of MDA, and increases of GSH at each time in renal tissue (P < 0.05). There were no significant difference between IPreC and IPostC (P> 0.05).
The mRNA and protein expression of SOD was evaluated by Real Time RT-PCR and Western blotting. Compared with Sham group, the IRI rats resulted in significant down-regulation of SOD mRNA and protein expression in renal (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant up-regulation of SOD mRNA and protein expression at 1 h, 6 h, and 24 h (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
3. The antiinflammatory mechanism of IPostC on renal IRI in rats
compared with Sham group, the IRI rats resulted in significant increases ofthe MPO activity in renal tissue at 1 h, 3 h, 6 h, 12 h and 24 h (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant decreases of the MPO activitiy at each time (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
The mRNA and protein expression of COX-1 and COX-2 were evaluated by Real Time RT-PCR and Western blotting. Compared with Sham group, the IRI rats resulted in significant up-regulation of COX-2 expression in renal (P < 0.05); while Compared with I/R group IPreC and IPostC treatments resulted in significant down-regulation of COX-2 expression at 1.5 h, 3 h, 6 h, 12 h and 24 h (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
4. The antiapoptosis mechanism of IPostC against renal IRI in rat
compared with Sham group, the IRI rats resulted in significant increases of the apoptosis cell in renal tubular at 6 h and apoptosis index (AI) was significantly increased (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant decreases of the apoptosis cell and AI was significantly decreased (P < 0.05) in renal tubular at 6 h (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
The mRNA and protein expressiones of Bcl-2 and Bax were evaluated by Real Time RT-PCR and Western blotting. Compared with Sham group, the IRI rats resulted in significant down-regulation of Bcl-2 mRNA and protein expression, and up-regulation of Bax mRNA and protein expression in renal and increase of Bcl-2/Bax (P < 0.05); while compared with I/R group IPreC and IPostC treatments resulted in significant up-regulation of Bcl-2 and down-regulation of Bax expression in renal (P < 0.05) and increase of Bcl-2/Bax. There were no significant difference between IPreC and IPostC (P > 0.05).
Conclusions
1. The function and structure of renal tissue were damaged by renal ischemic reperfusion in rats with the increase of the level of Cr and BUN, the damage of renal tubula and glomerulum, the elevation of MDA and MPO, the activity decreasing of GSH、SOD、CAT and GSH-Px, the decreasing of SGD mRNA and protein expression, the elevation of COX-2 mRNA and protein expression, the increasing of cell apoptosis, the decreasing of Bcl-2 mRNA and protein expression, and the increasing of Bax mRNA and protein expression.
2. Postconditioning was effectively protected kidney against IRI with the decrease of the level of Cr and BUN, and the improvement of the renal morphological features.
3. The mechanism of ischemic postconditioning against renal IRI may be related to antioxidative effect on the reducing the free radical, inhibiting lipid peroxidation, increasing the activity of antioxidative enzyme and SOD mRNA and protein expression, which improve antioxidative ability of kidney.
4. The mechanism of ischemic postconditioning against renal IRI may be related to anti-inflammatory effect on the inhibiting of PMN aggregation, the mRNA and protein expression of COX-2, and the producing of inflammatory mediator.
5. The mechanism of ischemic postconditioning against renal IRI may be associated to antiapoptosis effect by up-regulating Bcl-2 mRNA and protein expression and down-regulating Bax mRNA and protein expression.
6. The protective effect and mechanism of postconditoning against renal IRI were similar to that of ischemic preconditioning.
7. This study may not only provide a novel approach for clinic application, but also a useful theoretical and practival evidence for treating renal IRI.
肾脏是高灌流、对缺血-再灌注易受损伤的器官。缺血-再灌注损伤(ischemia reperfusion injury,IRI)在许多肾脏疾病,例如:肾移植、肾部分切除术、肾动脉血管成形术、动脉分流术、意外创伤、肾积水和输尿管手术过程中均会发生,是临床上导致急性肾功能衰竭的主要原因之一,死亡率较高,且存活的患者也会发生不同程度的慢性肾功能损害。因此,寻找防治肾脏缺血-再灌注损伤的方法与措施一直是近年来研究的热点的问题。
缺血预处理(ischemic preconditioning,IPreC)是目前公认的一种有效的抗器官组织缺血-再灌注损伤的机械性干预措施。1999年,Toosy等证实给予肾脏几个短暂的停灌/再灌处理,可以对后来发生的长时间的缺血损伤有比较明显的保护作用。但是,缺血预处理必须在IRI发生之前进行,这对于许多无法预期的肾脏缺血性疾病是不可能实现的,例如:在肾移植中,肾源的供给许多是无法预料的,也不可能有进行缺血预处理的时机,使缺血预处理的临床应用受到很大的限制。
缺血后处理(ischemic postconditioning,IPostC)是2003年由Vinten-Johansen's研究小组提出了一种新的机械性干预措施,即在心肌缺血发生之后,再灌注开始时给予3个短暂循环的再灌/停灌的处理。这种新的干预措施可以缩小心梗面积、保护内皮功能、减轻细胞水肿、减少缺血梗死区中性粒细胞的聚集和改善心功能,对心肌缺血-再灌注损伤有比较明显的保护作用,且作用程度与缺血预处理相似。与缺血预处理不同,缺血后处理是在组织器官缺血之后才实施,在临床上应用具有“简单、可行、有效”三大特点,目前被认为是一种防治缺血性疾病的新的机械性抗损伤措施,广泛地被应用于抗器官组织缺血-再灌注损伤的防治。
因此,本研究探讨了缺血后处理对肾脏IRI的保护作用,通过与缺血预处理相比较,从整体、细胞和分子水平上阐明缺血后处理抗大鼠肾脏IRI的作用机制,本研究可为外科抗肾脏缺血-再灌注损伤提供新的策略,也可为缺血后处理防治肾脏缺血-再灌注损伤的应用提供理论和实验依据。
[方法]
SPF级SD雄性大鼠,体重:180～220 g,随机分为①假手术组(Sham组):仅行开腹右肾切除,左肾蒂分离,不夹闭;②缺血-再灌注组(I/R组):开腹右肾切除,左肾蒂分离,无创血管夹夹闭45 min;③缺血预处理组(IPreC组):开腹右肾切除,左肾蒂分离,行3个循环夹闭2 min/再灌5 min预处理后,无创血管夹夹闭45 min;④缺血后处理组(IPostC组):开腹右肾切除,左肾蒂分离,无创血管夹夹闭45 min后,行6个循环夹闭10 sec/再灌10 sec后处理,各组再灌24 h。
本研究分两个部分:
1.缺血后处理抗大鼠肾脏缺血-再灌注损伤作用
应用分光分析法测定血清肌酐(Cr)、尿素氮(BUN)评价肾功能;HE染色观察肾组织病理形态学改变,评价缺血后处理抗大鼠肾脏缺血-再灌注损伤作用。
2.缺血后处理抗大鼠肾缺血-再灌注损伤的机制研究
分别从以下3方面进行探讨:
A从抗氧化途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制
应用分光分析法测定肾组织丙二醛(MDA)、还原性谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)活性:采用Real Time RT-PCR和Western blotting法分别测定SOD mRNA和蛋白表达情况,探讨缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制。
B从抗炎途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制
应用分光分析法测定肾组织中性粒细胞髓过氧化物酶(MPO)活性,采用Real Time RT-PCR和Western blotting法分别测定环氧酶(COX-1,COX-2)mRNA和蛋白表达情况,探讨缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制。
C从抗细胞凋亡途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制
应用DNA琼脂糖凝胶电泳法和末端脱氧核苷酸转移酶介导dUTP缺口末端标记法(TUNEL法)检测大鼠肾组织细胞凋亡发生情况;采用Real TimeRT-PCR和Western blotting法分别测定Bcl-2、Bax mRNA和蛋白的表达情况,探讨缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制。
[结果]
1.缺血后处理抗大鼠肾脏缺血-再灌注损伤作用
①肾功能的评价
与Sham组比较,I/R、IPreC和IPostC组的Cr及BUN水平明显升高(P＜0.05);与I/R组比较,IPreC和IPostC组的Cr及BUN水平明显降低(P＜0.05),IPreC和IPostC组Cr及BUN水平无明显差异(P＞0.05)。
②肾组织病理学观察
Sham组肾小球、肾小管没有发现明显的形态学改变,I/R组肾小管上皮细胞肿胀,出现水样变性和空泡变性,肾小管扩张,内可见管型和坏死脱落细胞,少量管腔内有蛋白性液体积聚,部分肾小管结构毁损,间质充血水肿,大量炎性细胞浸润,管周血管明显扩张淤血;IPreC和IPostC组肾小球轻度淤血,少量肾小管上皮细胞轻度水肿,空泡变性,少见管型,间质充血水肿,有少量炎性细胞浸润,管周稍有淤血。
2.从抗氧化途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用机制
①各氧化指标的变化
与Sham组比较,I/R、IPreC和IPostC组的MDA浓度明显升高,GSH浓度、SOD、CAT和GSH-Px活性明显降低(P＜0.05);与I/R组比较,IPreC和IPostC组的MDA浓度明显降低,GSH水平SOD、CAT和GSH-Px活性明显升高(P＜0.05),IPreC和IPostC组各个指标水平无明显差异(P＞0.05)。
②SOD mRNA和蛋白表达
与Sham组比较,I/R、IPreC和IPostC组的SOD mRNA和蛋白表达明显下降(P＜0.05),与I/R组比较,IPreC和IPostC组的SOD mRNA和蛋白表达相对升高,IPreC和IPostC相比,SOD mRNA和蛋白表达无明显差异(P＞0.05)。
3.从抗炎途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制
①MPO活性的变化
与Sham组比较,I/R、IPreC和IPostC组的MPO活性明显升高(P＜0.05);与I/R组比较,IPreC和IPostC组的MPO活性明显降低(P＜0.05)。
②COX蛋白表达
各组COX-1 mRNA和蛋白表达无统计学差异。与Sham组比较,I/R、IPreC和IPostC组的COX-2 mRNA和蛋白表达明显升高(P＜0.05),与I/R组比较,IPreC和IPostC组COX-2的mRNA和蛋白表达明显降低(P＜0.05),IPreC和IPostC相比,COX-2的mRNA和蛋白表达无明显差异(P＞0.05)。
4.从抗细胞凋亡途径研究缺血后处理抗大鼠肾脏缺血-再灌注损伤作用的机制
①肾小管上皮细胞凋亡的状况
与Sham组比较,I/R、IPreC和IPostC细胞凋亡数明显增加,凋亡指数(AI)明显增高(P＜0.05);与I/R组相比较,IPreC和IPostC细胞凋亡数明显减少,AI明显降低(P＜0.05),IPreC和IPostC组AI无明显差异(P＞0.05)。
②Bcl-2、Bax mRNA和蛋白表达
与Sham组比较,I/R、IPreC和IPostC组的Bcl-2 mRNA和蛋白表达明显下降,Bax mRNA和蛋白表达相对升高,Bcl-2/Bax下降(P＜0.05);与I/R组比较,IPreC和IPostC组的Bcl-2 mRNA和蛋白表达相对升高,Bax mRNA和蛋白表达相对降低,Bcl-2/Bax明显升高(P＜0.05),IPreC和IPostC相比,Bcl-2和Bax的mRNA和蛋白表达无明显差异(P＞0.05)。
[结论]
1.肾缺血-再灌注使大鼠肾功能和结构受损,表现为Cr和BUN升高,肾小球、肾小管受损,MDA、MPO升高,GSH、SOD、CAT和GSH-Px活性降低,SOD的mRNA和蛋白表达下降,COX-2 mRNA和蛋白表达升高,肾组织细胞凋亡增加,Bcl-2 mRNA和蛋白表达降低,Bax mRNA和蛋白表达升高。
2.缺血后处理能减轻Cr和BUN水平,减轻肾组织结构的损伤,具有显著的抗大鼠肾缺血-再灌注损伤的作用。
3.缺血后处理抗大鼠肾缺血-再灌注损伤作用机制与抗氧化有关,可能是通过清除氧自由基,抑制脂质过氧化,升高组织抗氧化物酶的活性和蛋白表达,提高肾组织的抗氧化能力。
4.缺血后处理抗大鼠肾缺血-再灌注损伤作用机制与抗炎有关,可能是通过抑制中性粒细胞聚集,抑制COX-2 mRNA和蛋白的表达,从而抑制炎症介质的产生。
5.缺血后处理抗大鼠肾缺血-再灌注损伤作用机制与抗细胞凋亡作用有关,可能是通过调控细胞凋亡相关基因Bcl-2/Bax mRNA和蛋白表达。
6.缺血后处理抗大鼠肾缺血-再灌注损伤作用及其机制与缺血预处理有相似之处。
7.缺血后处理抗大鼠肾缺血-再灌注损伤的作用及机制的研究有助于为防治肾脏缺血-再灌注损伤提供理论和实验依据,为外科抗肾脏缺血-再灌注损伤提供新的策略。
Background and objective
Kidney is easily subjected to ischemic reperfusion injury due to its abundance of blood supply. The temporary discontinuation of renal blood supply is encountered in many clinical situations, such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass, aortic bypass surgery, accidental or iatrogenic trauma, sepsis, hydronephrosis and elective urological operations. Acute renal failure (ARF) resulting from renal ischemia reperfusion injury (IRI) remains a major clinical problem because of its frequent occurrence and high mortality. How to treat the renal IRI is always keeping in attention.
Currently, ischemic preconditioning (IPreC) is a well-known method in treating organ IRI. Toosy demonstrated that several short cycles of ischemia and reperfusion before renal ischemia could effectively render the renal resistant to a subsequent ischemic insult, although extensive researches have demonstrated that IPreC reduced renal IRI. However, IPreC is clinically feasible only when the occurrence of ischemia is predictable. It is fail to treat unpredictable accident events. It is need to find out other useful method to amelioration renal IRI.
Compared to ischemia, the onset of reperfusion is more predictable. In 2003, Vinten-Johnsen and his colleagues reported that brief episodes of myocardial ischemia and reperfusion employed during reperfusion after a prolonged ischemic insult had been demonstrated to play a cardioprotective role. This phenomenon was termed "Ischemic postconditioning (IPostC)". In a dog model, IPostC limited infarct size, reduced tissue edema and poly morphonuclear neutrophil accumulation in the area at risk myocardium, and improved endothelial function. It has been suggested that IPostC is as effective as IPreC in limiting infarct size and preserving postischemic endothelial function. Numerous studies demonstrated that IPostC was a simple and harmless method which provided a new tool to protect organ from IRI.
Therefore, we investigated the protective role and mechanism of ischemic postconditioning against renal IRI in rats and compared the results with IPreC. Our study may not only provide a useful theoretical and practical evidence for reducing renal IRI, but also provide a novel approach for clinic application.
Methods
Adult male Sprague-Dawley rats (180～220 g) were randomly separated into four groups: a) Sham group: the right kidneys were removed only; b) IR group: after right nephrectomy, kidneys were subjected to 45 min of ischemia; c) IPreC group: kidneys were subjected to three cycles of 2 min ischemia separated by 5 min reperfusion periods before 45 min of ischemia; d) IPostC group: kidneys were subjected to 45 min of ischemia followed by six cycles of 10 sec reperfusion separated by 10 sec ischemia. Rats were sacrificed and kidneys were harvested after reperfusion. Each group comprised eight rats. The following two aspects were investgated.
1. The protective effects of IPostC on renal IRI in rats.
Serum Cr and BUN were evaluated by Cr assay kits and BUN assay kits at 24 h after IRI, respectively. The renal pathologic changes were observed by HE-staining at 24 h after IRI.
2. The mechanism associated with renal IRI
A The antioxidative mechanism of IPostC against renal IRI in rat
SOD, CAT, and GSH-Px activity were investigated. GSH and MDA at 1 h, 3 h, 6 h, 12 h, and 24 h were measured. The mRNA and protein expression of SODat 1 h, 6 h and 24 h were evaluated by Real Time RT-PCR and Western blotting.
B The antiinflammatory mechanism of IPostC against renal IRI in rat
MPO activity at 1 h, 3 h, 6 h, 12 h and 24 h was investigated.The mRNA andprotein expression of SOD at 1 h, 3 h, 6 h, 12 h and 24 h were evaluated by RealTime RT-PCR and Western blotting.
C The antiapoptosis mechanism of IPostC against renal IRI in rat
Apoptosis was compared by TUNEL method; Real time RT-PCR assay for theBcl-2 and Bax mRNA at 6 h was evaluated; Western blotting assay for the proteinexpression of Bcl-2 and Bax at 6 h was evaluated.
Results
1. The protective effects of IPostC on renal IRI in rats
The renal function of rats 24 h after IRI was significantly different between groups. Rats subjected to IRI showed significant increase in serum Cr and BUN compared with Sham group (P < 0.05). The renal function changes caused by IRI were significantly improved by IPreC and IPostC treatments (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
Renal IRI resulted in significant renal injury as evidenced by tubular necrosis, medullary hemorrhage, congestion, and development of proteinaceous casts. In contrast, treatments of IPreC and IPostC ameliorated these severe renal damages. According to Jablonski scores, 45 min renal ischemia followed by 24 h reperfusion resulted in severe acute tubular necrosis. Quantitative analysis showed a dramatically decreased score in both IPreC group and IPostC group compared with IRI group (P < 0.05). There were no significant difference between IPreC and IPostC (P> 0.05).
2. The antioxidative mechanism of IPostC against renal IRI in rat
Compared with Sham group, the I/R group resulted in significant down-regulation of the activities of SOD, CAT, and GSH-Px in renal at 1.5 h, 3 h, 6 h, 12 h and 24 h (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant up-regulation of their activities at each time (P < 0.05); compared with Sham group, the IRI rats resulted in significant increases of the levels of MDA, and decreases of GSH in renal tissue at 1 h, 3 h, 6 h, 12 h and 24 h. While compared with I/R group, IPreC and IPostC treatments resulted in significant decreases of the levels of MDA, and increases of GSH at each time in renal tissue (P < 0.05). There were no significant difference between IPreC and IPostC (P> 0.05).
The mRNA and protein expression of SOD was evaluated by Real Time RT-PCR and Western blotting. Compared with Sham group, the IRI rats resulted in significant down-regulation of SOD mRNA and protein expression in renal (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant up-regulation of SOD mRNA and protein expression at 1 h, 6 h, and 24 h (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
3. The antiinflammatory mechanism of IPostC on renal IRI in rats
compared with Sham group, the IRI rats resulted in significant increases ofthe MPO activity in renal tissue at 1 h, 3 h, 6 h, 12 h and 24 h (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant decreases of the MPO activitiy at each time (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
The mRNA and protein expression of COX-1 and COX-2 were evaluated by Real Time RT-PCR and Western blotting. Compared with Sham group, the IRI rats resulted in significant up-regulation of COX-2 expression in renal (P < 0.05); while Compared with I/R group IPreC and IPostC treatments resulted in significant down-regulation of COX-2 expression at 1.5 h, 3 h, 6 h, 12 h and 24 h (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
4. The antiapoptosis mechanism of IPostC against renal IRI in rat
compared with Sham group, the IRI rats resulted in significant increases of the apoptosis cell in renal tubular at 6 h and apoptosis index (AI) was significantly increased (P < 0.05); while compared with I/R group, IPreC and IPostC treatments resulted in significant decreases of the apoptosis cell and AI was significantly decreased (P < 0.05) in renal tubular at 6 h (P < 0.05). There were no significant difference between IPreC and IPostC (P > 0.05).
The mRNA and protein expressiones of Bcl-2 and Bax were evaluated by Real Time RT-PCR and Western blotting. Compared with Sham group, the IRI rats resulted in significant down-regulation of Bcl-2 mRNA and protein expression, and up-regulation of Bax mRNA and protein expression in renal and increase of Bcl-2/Bax (P < 0.05); while compared with I/R group IPreC and IPostC treatments resulted in significant up-regulation of Bcl-2 and down-regulation of Bax expression in renal (P < 0.05) and increase of Bcl-2/Bax. There were no significant difference between IPreC and IPostC (P > 0.05).
Conclusions
1. The function and structure of renal tissue were damaged by renal ischemic reperfusion in rats with the increase of the level of Cr and BUN, the damage of renal tubula and glomerulum, the elevation of MDA and MPO, the activity decreasing of GSH、SOD、CAT and GSH-Px, the decreasing of SGD mRNA and protein expression, the elevation of COX-2 mRNA and protein expression, the increasing of cell apoptosis, the decreasing of Bcl-2 mRNA and protein expression, and the increasing of Bax mRNA and protein expression.
2. Postconditioning was effectively protected kidney against IRI with the decrease of the level of Cr and BUN, and the improvement of the renal morphological features.
3. The mechanism of ischemic postconditioning against renal IRI may be related to antioxidative effect on the reducing the free radical, inhibiting lipid peroxidation, increasing the activity of antioxidative enzyme and SOD mRNA and protein expression, which improve antioxidative ability of kidney.
4. The mechanism of ischemic postconditioning against renal IRI may be related to anti-inflammatory effect on the inhibiting of PMN aggregation, the mRNA and protein expression of COX-2, and the producing of inflammatory mediator.
5. The mechanism of ischemic postconditioning against renal IRI may be associated to antiapoptosis effect by up-regulating Bcl-2 mRNA and protein expression and down-regulating Bax mRNA and protein expression.
6. The protective effect and mechanism of postconditoning against renal IRI were similar to that of ischemic preconditioning.
7. This study may not only provide a novel approach for clinic application, but also a useful theoretical and practival evidence for treating renal IRI.
引文
[1]陈主初,郭恒怡,王树人.缺血-再灌注损伤.病理生理学.2005.191-201.
[2]Tullius SQ,Tilney NL.Both alloantigen-dependent and independent factors influence chronic allograft rejection[J].Transplantation,1995,59(3):313-318.
[3]Giral-Classe M,Hourmant M,Cantarovich F,et al.Contribution of prolonged emia and donor age to chronic renal allograft dysfunction[J].Am J Soc Nephrol,2000,11: 1317-1324.
[4]Wang Y,Ji HX,Xing SH,et al.SP600125,a selective JNK inhibitor,protects ischemic renal injury via suppressing the extrinsic pathways of apoptosis[J].Life Sci,2007,80(22):2067-75.
[5]Mahmoud IM,Hussein Ael A,Sarhan ME,et al.Role of combined L-arginine and prostagIandin El in renal ischemia-reperfusion injury[J].Nephron Physiol,2007,105(4):p57-65.
[6]Kaudel CP,Frink M,Schmiddem U,et al.FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia;impact on long-term survival and T-lymphocyte tissue infiltration[J].Transplant Proc,2007,39(2):499-502.
[7]Fuller TF,Rose F,Singleton KD,et al.Glutamine donor pretreatment in rat kidney transplants with severe preservation reperfusion injury[J].J Surg Res,2007,140(1):77-83.
[8]Grenz A,Eckle T,Zhang H,et al.Use of a hanging-weight system for isolated renal artery occlusion during ischemic preconditioning in mice[J].Am J Physiol Renal Physiol,2007,292(1):F475-85.
[9]Jiang SH,Liu CF,Zhang XL,et al.Renal protection by delayed ischaemic preconditioning is associated with inhibition of the inflammatory response and NF-kappaB activation[J].Cell Biochem Funct,2007,25(3):335-43.
[10]Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003,285(2):H579-88.
[11]褚薇薇,武步强,沙焕臣,et al.缺血后处理对缺血-再灌注大鼠肠黏膜的抗损伤作用[J].西安交通大学学报(医学版),2007,28(2):149-51.
[12]武步强,褚薇薇,贺国洋,et al.缺血后处理对缺血-再灌注肝脏的抗损伤作用研究[J].昆明医学院学报,2005,3:64-67.
[1]Tullius SQ,Tilney NL.Both alloantigen-dependent and independent factors influence chronic allograft rejection[J].Transplantation,1995,59(3):313-318.
[2]Giral-Classe M,Hourmant M,Cantarovich F,et al.Contribution of prolonged emia and donor age to chronic renal allograft dysfunction[J].Am J Soc Nephrol,2000,11:1317-1324.
[3]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-36.
[4]Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Cite Physiol,2003,285(2):H579-88.
[5]Kloner RA,Rezkalla SH.Preconditioning,postconditioning and their application to clinical cardiology[J].Cardiovasc Res,2006,70(2):297-307.
[6]Liu X,Chen H,Zhan B,et al.Attenuation of reperfusion injury by renal ischemic postconditioning:the role of NO[J].Biochem Biophys Res Commun,2007,359(3):628-34.
[7]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[8]chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[9]Jablonski P,Howden BO,Rae DA,et al.An experimental model for assessment of renal recovery from warm ischemia[J].Transplantation,1983,35(3):198-204.
[10]Hausenloy DJ,Yellon DM.Preconditioning and postconditioning:united at reperfusion [J].Pharmacol Yher,2007,116(2):173-91.
[11]Toosy N,McMorris EL,Grace PA,et al.Ischaemic preconditioning protects the rat kidney from reperfusion injury[J].BJU Int,1999,84(4):489-94.
[12]Hernandez DJ,Roberts WB,Miles-Thomas J,et al.Can ischemic preconditioning ameliorate renal ischemia-reperfusion injury in a single-kidney porcine model?[J].J Endourol,2008,22(11):2531:6.
[13]Timsit MO,Gadet R,Ben Abdennebi H,et al.Renal ischemic preconditioning improves recovery of kidney function and decreases alpha-smooth muscle actin expression in a rat model[J].J Urol,2008,180(1):388-91.
[14]Kin H,Zatta AJ,Lofye MT,et al.Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine[J].Cardiovasc Res,2005,67:124-33.
[15]Philipp S,Yang XM,Cui L,et al.Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade[J].Cardiovasc Res,2006,70(2):308-14.
[16]Staat P,Rioufol G,Piot C,et al.Postconditioning the human heart[J].Circulation,2005,112(14):2143-8.
[17]Sun K,Liu ZS,Sun Q.Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning[J].World J Gastroenterol,2004,10(13):1934-8.
[18]Zhao H,Sapolsky RM,Steinberg GK.Interrupting reperfusion as a stroke therapy:ischemic postconditioning reduces infarct size after focal ischemia in rats[J].J Cereb Blood Flow Metab,2006,26(9):1114-21.
[1]Wang HC,Zhang HF,Guo WY,et al.Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation:role of peroxynitrite formation[J].Apoptosis,2006,11(8):1453-60.
[2]Wang C,Neff DA,Krolikowski JG,et al.The influence of B-cell lymphoma 2 protein,an antiapoptotic regulator of mitochondrial permeability transition,on isoflurane-induced and ischemic postconditioning in rabbits[J].Anesth Analg,2006,102(5):1355-60.
[3]Loukogeorgakis SP,Panagiotidou AT,Yellon DM,et al.Postconditioning protects against endothelial ischemia-reperfusion injury in the human forearm[J].Circulation,2006, 113(7):1015-9.
[4]Tsang A,Hausenloy DJ,Mocanu MM,et al.Postconditioning:a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway[J].Circ Res,2004,95(3):230-2.
[5]Philipp S,Yang XM,Cui L,et al.Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade[J].Cardiovasc Res,2006,70(2):308-14.
[6]Ovize M.[Postconditioning:lethal reperfusion injury as a therapeutic target][J].Ann Cardiol Angeiol(Paris),2006,55(2):66-9.
[7]陈主初,郭恒怡,王树人.缺血-再灌注损伤.病理生理学.2005.191-201.
[8]Sun HY,Wang NP,Kerendi F,et al.Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload[J].Am J Physiol Heart Circ Physiol,2005,288(4):H1900-8.
[9]Vinten-Johansen J,Zhao ZQ,Zatta AJ,et al.Postconditioning--A new link in nature's armor against myocardial ischemia-reperfusion injury[J].Basic Res Cardiol,2005,100(4):295-310.
[10]Sun K,Liu ZS,Sun Q.Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning[J].World J Gastroenterol,2004,10(13):1934-8.
[11]Dosenko VE,Nagibin VS,Tumanovskaya LV,et al.Postconditioning prevents apoptotic necrotic and autophagic cardiomyocyte cell death in culture[J].Fiziol Zh,2005,51(3):12-7.
[12]Singh D,Kaur R,Chander V,et al.Antioxidants in the prevention of renal disease[J].J Med Food,2006,9(4):443-50.
[13]Yamanobe T,Okada F,Iuchi Y,et al.Deterioration of ischemia/reperfusion-induced acute renal failure in SOD1-defcient mice[J].Free Radic Res,2007,41(2):200-7.
[14]Zima AV,Blatter LA.Redox regulation of cardiac calcium channels and transporters[J].Cardiovasc Res,2006,71(2):310-21.
[15]Wang YH,Wang WY,Chang CC,et al.Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation[J].J Biomed Sci,2006,13(1):127-41.
[16]Johnson KJ,Weinberg JM.Postischemic renal injury due to oxygen radicals[J].Curr Opin Nephrol Hypertens,1993,2(4):625-35.
[17]Dobashi K,Ghosh B,Orak JK,et al.Kidney ischemia-reperfusion:modulation of antioxidant defenses[J].Mol Cell Biochem,2000,205(1-2):1-11.
[18]Singla DK,Kaur K,Sharma AK,et al.Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injury[J].Can J Physiol Pharmacol,2007,85(3-4):439-43.
[19]Ellis EM.Reactive carbonyls and oxidative stress:potential for therapeutic intervention [J].Pharmacol Ther,2007,115(1):13-24.
[20]Lee WY,Lee JS,Lee SM.Protective effects of combined ischemic preconditioning and ascorbic acid on mitochondrial injury in hepatic ischemia/reperfusion[J].J Surg Res,2007,142(1):45-52.
[21]Kotani Y,Ishino K,Osaki S,et al.Efficacy of MCI-186,a free-radical scavenger and antioxidant,for resuscitation of nonbeating donor hearts[J].J Thorac Cardiovasc Surg,2007,133(6):1626-32.
[22]Lee WY,Lee SM.Ischemic preconditioning protects post-ischemic oxidative damage to mitochondria in rat liver[J].Shock,2005,24(4):370-5.
[23]Penna C RR,Mancardi D,Raimondo D,Cappello S,,Gattullo D ea.Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism,mitochondrial ATP sensitive K+channel and protein kinase C activation[J].Bas Res Cardiol,2006,101(2):180-189.
[24]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[25]Chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[26]Aydin A,Orhan H,Sayal A,et al.Oxidative stress and nitric oxide related parameters in type Ⅱ diabetes mellitus:effects of glycemic control[J].Clin Biochem,2001,34(1):65-70.
[27]Kerimova AA,Atalay M,Yusifov EY,et al.Antioxidant enzymes;possible mechanism of gold compound treatment in rheumatoid arthritis[J].Pathophysiology,2000,7(3):209-213.
[28]Chen H,Xing B,Liu X,et al.Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury[J].Eur J Pharmacol,2008,581(3):306-14.
[29]Chien CT,Chen CF,Hsu SM,et al.Protective mechanism of preconditioning hypoxia attenuates apoptosis formation during renal ischemia/reperfusion phase[J].Transplant Proc,1999,31(5):2012-3.
[30]Hansen JM,Choe HS,Carney EW,et al.Differential antioxidant enzyme activities and glutathione content between rat and rabbit conceptuses[J].Free Radic Biol Med,2001,30(10):1078-88.
[31]Ugochukwu NH,Cobourne MK.Modification of renal oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with extracts from Gongronema latifolium leaves[J].Clin Chim Acta,2003,336(1-2):73-81.
[32]Ohkawa H,Ohishi N,Yagi K.Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction[J].Anal Biochem,1979,95(2):351-8.
[33]Rubinstein I,Abassi Z,Milman F;et al.Hyperbaric oxygen treatment improves GFR in rats with ischaemia/reperfusion renal injury:a possible role for the antioxidant/oxidant balance in the ischaemic kidney[J].Nephrol Dial Transplant,2009,24(2):428-36.
[34]Tenorio-Velazquez VM,Barrera D,Franco M,et al.Hypothyroidism attenuates protein tyrosine nitration,oxidative stress and renal damage induced by ischemia and reperfusion:effect unrelated to antioxidant enzymes activities[J].BMC Nephrol,2005,6:12.
[35]Kaur H,Padi SS,Chopra K.Attenuation of renal ischemia-reperfusion injury by trimetazidine:evidence of an in vivo antioxidant effect[J].Methods Find Exp Clin Pharmacol,2003,25(10):803-9.
[36]Zurovsky Y,Eligal Z,Grossman S.Unilateral renal ischemia reperfusion in the rat:effect of blood volume trapped in the kidney,sucrose infusion,and antioxidant treatments[J].Exp Toxicol Pathol,1995,47(6):471-8.
[1]Vinten-Johansen J,Zhao ZQ,Zatta AJ,et al.Postconditioning-A new link in nature's armor against myocardial ischemia-reperfusion injury[J].Basic Res Cardiol,2005,100(4):295-310.
[2]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[3]Chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[4]Sadis C,Teske G,Stokman G,et al.Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway[J].PLoS ONE,2007,2(5):e469.
[5]Roelofs JJ,Rouschop KM,Leemans JC,et al.Tissue-type plasminogen activator modulates inflammatory responses and renal function in ischemia reperfusion injury[J].J Am Soc Nephrol,2006,17(1):131-40.
[6]Miura M,Fu X,Zhang QW,et al.Neutralization of Gro alpha and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury[J].Am J Pathol,2001,159(6):2137-45.
[7]Carden DL,Smith JK,Korthuis RJ.Neutrophil-mediated microvascular dysfunction in postischemic canine skeletal muscle.Role of granulocyte adherence[J].Circ Res,1990,66(5):1436-44.
[8]Furuichi K,Gao JL,Horuk R,et al.Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury[J].J Immunol,2008,181(12):8670-6.
[9]Kin H,Zhao ZQ,Sun HY,et al.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J].Cardiovasc Res,2004,62(1):74-85.
[10]Okusa MD.The inflammatory cascade in acute ischemic reperfussion renal failure[J].Nephron Exp Nephrol,2002,90:133-138.
[11]Ross R.Mechanism of disease:atherosclerosis,an inflammatory disease[J].New Engl J Med,1999,340:115-21.
[12]Sinisalo J,Paronen J,Mattila K,et al.Relation of inflammation to vascular function in patients with coronary heart disease[J].Atherosclerosis,1999,149(403-11).
[13]Hausknecht B,Voelkl S,Riess R,et al.Expression of cyclooxygenase-2 in biopsies obtained from human transplanted kidneys undergoing rejection[J].Transplantation,2003,76:109-14.
[14]Carla Q F,Niels O.S.Cm,He'lady S.P,et al.Cyclooxygenase 1 and/or 2 blockade ameliorates the renal tissue damage triggered by ischemia and reperfusion injury[J]. International Immunopharmacology 2005,5:79-84.
[15]Feitoza CQ,Camara NO,Pinheiro HS,et al.Cyclooxygenase 1 and/or 2 blockade ameliorates the renal tissue damage triggered by ischemia and reperfusion injury[J].Int Immunopharmacol,2005,5(1):79-84.
[16]Matsuyama M,Yoshimura R,Hase T,et al.Study of cyclooxygenase-2 in renal ischemia-reperfusion injury[J].Transplant Proc,2005,37(1):370-2.
[17]Chan CC,Rodger IW.Selective cyclooxygenase-2 inhibitors as potential therapeutic agents for inflammatory diseases[J].Adv Exp Med Biol,1997,407:157-61.
[1]Lopez-Neblina F,Toledo AH,Toledo-Pereyra LH.Molecular biology of apoptosis in ischemia and reperfusion[J].J Invest Surg,2005,18(6):335-50.
[2]Padanilam BJ.Cell death induced by acute renal injury:a perspective on the contributions of apoptosis and necrosis[J].Am J Physiol Renal Physiol,2003,284(4):F608-27.
[3]Tsujimoto Y.Cell death regulation by the Bcl-2 protein family in the mitochondria[J].J Cell Physiol,2003,195(2):158-67.
[4]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[5]Chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[6]Liu X,Chen H,Zhan B,et al.Attenuation of reperfusion injury by renal ischemic postconditioning:the role of NO[J].Biochem Biophys Res Commun,2007,359(3):628-34.
[7]Kher A,Meldrum KK,Hile KL,et al.Aprotinin improves kidney function and decreases tubular cell apoptosis and proapoptotic signaling after renal ischemia-reperfusion[J].J Thorac Cardiovasc Surg,2005,130(3):662-9.
[8]Kishino M,Yukawa K,Hoshino K,et al.Deletion of the kinase domain in death-associated protein kinase attenuates tubular cell apoptosis in renal ischemia-reperfusion injury[J].J Am Soc Nephrol,2004,15(7):1826-34.
[9]Hou Q,Cymbalyuk E,Hsu SC,et al.Apoptosis modulatory activities of transiently expressed Bcl-2:roles in cytochrome C release and Bax regulation[J].Apoptosis,2003,8(6):617-29.
[10]Saito M,Korsmeyer SJ,Schlesinger PH.BAX-dependent transport of cytochrome c reconstituted in pure liposomes[J].Nat Cell Biol,2000,2(8):553-5.
[11]Willis SN,Adams JM.Life in the balance:how BH3-only proteins induce apoptosis[J].Curr Opin Cell Biol,2005,17(6):617-25.
[12]Dejean LM,Martinez-Caballero S,Manon S,et al.Regulation of the mitochondrial apoptosis-induced channel,MAC,by BCL-2 family proteins[J].Biochim Biophys Acta,2006,1762(2):191-201.
[13]Vlahakis SR,Badley AD.Influence of proteasome inhibitors on apoptosis[J].Curr Opin Clin Nutr Metab Care,2006,9(1):42-7.
[14]Scarabelli TM,Knight R,Stephanou A,et al.Clinical implications of apoptosis in ischemic myocardium[J].Curr Probl Cardiol,2006,31(3):181-264.
[15]Oakes SA,Lin SS,Bassik MC.The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins[J].Curr Mol Med,2006,6(1):99-109.
[16]Chen H,Xing B,Liu X,et al.Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury[J].Eur J Pharmacol,2008,581(3):306-14.
[17]Yokozawa T,Chen CP,Rhyu DY,et al.Potential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo[J].Nephron,2002,92(1):133-41.
[18]Vinten-Johansen J,Zhao ZQ,Zatta AJ,et al.Postconditioning-A new link in nature's armor against myocardial ischemia-reperfusion injury[J].Basic Res Cardiol,2005,100(4):295-310.
[19]褚薇薇.缺血后处理抗大鼠肠缺血-再灌拄损伤的作用及其机制研究[J].昆明医学 院博士学位论文,2007:75-82.
[20]Kerr JF,Wyllie AH,Currie AR.Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics[J].Br J Cancer,1972,26(4):239-57.
[21]Majno G;Joris I.Apoptosis,oncosis,and necrosis.An overview of cell death[J].Am J Pathol,1995,146(1):3-15.
[22]Li Y,Chopp M,Jiang N,et al.Induction of DNA fragmentation after 10 to 120 minutes of focal cerebral ischemia in rats[J].Stroke,1995,26(7):1252-7;discussion 1257-8.
[23]Kohli V,Selzner M,Madden JF,et al.Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver[J].Transplantation,1999,67(8):1099-105.
[24]Fliss H.Accelerated apoptosis in reperfused myocardium:friend of foe?[J].Basic Res Cardiol,1998,93(2):90-3.
[25]门秀丽,张连元,董淑云.牛磺酸对大鼠肢体缺血再灌注肺损伤时细胞凋亡的影响.[J].中国病理生理杂志,2004,20(3):4212-41.
[26]李彬,温笠,杨新东.大鼠肢体缺血再灌注损伤后细胞凋亡与Bcl-2和Bax蛋白表达的关系[J].温州医学院学报,2003,23(10):3012-3031.
[1]Zhao Z.Q.,Corvera J.S.,Halkos M.E.,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003.285(2):H579-88.
[2]Philipp S.,Critz S.D.,Cui L.,et al.Localizing extracellular signal-regulated kinase(ERK) in pharmacological preconditioning's trigger pathway[J].Basic Res Cardiol,2006.101(2):159-67.
[3]Darling C.E.,Jiang R.,Maynard M.,et al.Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts:role of ERK1/2[J].Am J Physiol Heart Circ Physiol,2005.289(4):H1618-26.
[4]van Vuuren D.,Genis A.,Genade S.,et al.Postconditioning the isolated working rat heart[J].Cardiovasc Drugs Ther,2008.22(5):391-7.
[5]Penna C.,Mancardi D.,Rastaldo R.,et al.Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling[J].Cardiovasc Res,2007.75(1):168-77.
[6]Staat R,Rioufol G.,Piot C.,et al.Postconditioning the human heart[J].Circulation,2005.112(14):2143-8.
[7]Darling C.E.,Solari P.B.,Smith C.S.,et al.'Postconditioning' the human heart:multiple balloon inflations during primary angioplasty may confer cardioprotection[J].Basic Res Cardiol,2007.102(3):274-8.
[8] Opie L.H. Cardiologists are living through exciting times. The example of postconditioning to protect the human heart during revascularization[J]. Ann Cardiol Angeiol (Paris), 2006. 55(2): 64-5.
[9] Kin H., Zhao Z.Q., Sun H.Y., et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004.62(1): 74-85.
[10] Yang X-M P.J., Cui L, Krieg T, Downey JM, Cohen MV. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J]. J Am Coll Cardiol, 2004. 44: 1103-10.
[11] Philipp SD D J., Cohen MV. Postconditioning must be initiated in less than lminute following reperfusion and is dependent on adenosine receptors and P13-kinase.[J]. Circulation 2004.110:III-168 [Abstract].
[12] Halkos M.E., Kerendi F., Corvera J.S., et al. Myocardial protection with postconditioning is not enhanced by ischemic preconditioning[J]. Ann Thorac Surg, 2004. 78(3): 961-9; discussion 969.
[13] Tsang A., Hausenloy D.J., Mocanu M.M., et al. Postconditioning: a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway[J]. Circ Res, 2004. 95(3): 230-2.
[14] Bolli R. Oxygen-derived free radicals and myocardial reperfusion injury: an overview[J]. Cardiovasc Drugs Ther, 1991. 5(Suppl 2): 249- 68.
[15] Lucches B.R. Complement, neutrophils and free radicals: mediators of reperfusion injury[J]. Arzneim-Forsch/Drug Res, 1994. 44: 420-32.
[16] Jeroudi M.O. H.C.J., Bolli R. Myocardial reperfusion injury: role of oxygen radicals and potential therapy with antioxidants[J]. Am J Cardiol, 1994. 73: 2B-7B.
[17] Herkert O D.I., Brandes RP, Hess J, Busse R, Gorlach A, . NADPH oxidase mediates tissue factor-dependent surface procoagulant activity by thrombin in human vascular smooth muscle cells[J]. Circulation, 2002.105: 2030- 6.
[18] Duilio C A.G, Kuppusamy P, DiPaula A, Becker LC, Zweier, JL. Neutrophils are primary source of O_2 radicals during reperfusion after prolonged myocardial ischemia[J]. Am J Physiol (Heart Circ Physiol), 2001. 280: H2649- 57.
[19] Vinten-Johansen J. Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury[J]. Cardiovasc Res, 2004. 61:481-97.
[20] Sun H.Y., Wang N.P., Kerendi E, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload[J]. Am J Physiol Heart Circ Physiol,2005. 288(4):H1900-8.
[21] Serviddio G, Di Venosa N., Federici A., et al. Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia-reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion[J], Faseb J, 2005.19(3): 354-61.
[22] PENNA C.R., MANCARDI D., RAIMGNDO D., et al. Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP sensitive K+channel and protein kinase C activation[J]. Bas Res Cardiol, 2006. 101(2):180-189.
[23] Downey J.M., Cohen M.V. A really radical observation-a comment on Penna et al. in Basic Res Cardiol (2006) 101:180-189[J]. Basic Res Cardiol, 2006.101(2): 190-1.
[24] Yang X.M., Philipp S., Downey J.M., et al. Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation[J]. Basic Res Cardiol, 2005.100(1): 57-63.
[25] Philipp S., Yang X.M., Cui L., et al. Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade[J]. Cardiovasc Res, 2006. 70(2): 308-14.
[26] Kin H., Zatta A.J., Lofye M.T., et al. Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine[J]. Cardiovasc Res, 2005. 67: 124-33.
[27] Kilpatrick EL N.P., Mentzer Jr RM, Lasley RD. Adenosine A3 agonist cardioprotection in isolated rat and rabbit hearts is blocked by the Al antagonist DPCPX[J]. Am J Physiol 2001. 281:H847-53.
[28] Jang Y., Xi J., Wang H., et al. Postconditioning prevents reperfusion injury by activating delta-opioid receptors[J]. Anesthesiology, 2008.108(2): 243-50.
[29] Zatta A.J., Kin H., Yoshishige D., et al. Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation[J]. Am J Physiol Heart Circ Physiol, 2008. 294(3): H1444-51.
[30] Wang J., Gao Q., Shen J., et al. [Kappa-opioid receptor mediates the cardioprotective effect of ischemic postconditioning][J]. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2007.36(1): 41-7.
[31] Zhao Z.-Q., SH-Y, Wang N.-P., et al. Hypoxic postconditioning attenuates cardiomyocyte apoptosis via inhibition of jnk and p38 kinases pathway[J]. J Mol Cell Cardiol, 2005. 38: 870.
[32] YANG X.M, DOWNEY J.M., COHEN M.V. Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation[J]. Bas Res Cardiol 2005.100: 57- 63.
[33] Zhao Z-Q S.H.-Y., Wang N-P, Kin H, Guyton RA, Vinten-Johansen J. Hypoxic postconditioning attenuates cardiomyocyte apoptosis via inhibition of jnk and p38 kinases pathway[J]. J Mol Cell Cardiol, 2005. 38: 870[Abstract].
[34] Mackman N. The role of the tissue factor-thrombin pathway in cardiac ischemia- reperfusion injury[J]. Semin Vasc Med 2003. 3: 193-8.
[35] Jobe L.J., Jiang R., Wang N.-P., et al. Tissue factor, factors Vila and Xa expression and local generation of thrombin in at risk myocardium occurs specifically during reperfusion[J]. Circulation, 2004.110(111-297).
[36] Jiang R.J., Mykytenko J., Zatta A.J., et al. Postconditioning reduces reperfusion injury by inhibiting the tissue factor-thrombin pathway in a closed-chest porcine model of ischemia- reperfusion [J]. Circulation, 2005.112(Suppl II): II-309[Abstract].
[37] Vinten-Johansen J Z.Z.-Q., Nakamura M, Jordan JE, Ronson RS,, Thourani VH e.a. Nitric oxide and the vascular endothelium in myocardial ischemia- reperfusion injurya. [J]. In: Das DKHeart in Stress 1999. 874:354-70.
[38] Lefer DJ N.K., Vinten-Johansen J, Ma X-L, Lefer AM. Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs[J]. Am J Physiol 1992. 263: H850- 6.
[39] Tsao PS A.N., Lefer DJ, Johnson III G, Lefer AM. . Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat[J]. Circulation, 1990. 82: 1402-12.
[40] Wang P Z.J. Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitritemediated reperfusion injury. [J]. J Biol Chem, 1996. 271:29223- 30.
[41] Johnson III G T.P., Lefer AM. Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion[J]. Crit Care Med, 1991.19:244- 52.
[42] Lefer DJ N.K., Johnston WE, Vinten-Johansen J. Antineutrophil and myocardial protecting action of SPM-5185, a novel nitric oxide (NO) donor, following acute myocardial ischemia . and reperfusion in dogs[J]. Circulation, 1993. 88:2337- 50.
[43] Cohen M.V. Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies.[J]. Cardiovasc Res, 2006. 70(2): 231-239
[44] Pagliaro P.R. R.R., Penna C, Mancardi D, Cappello S, Losano Gattullo D, et al. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway is involved in ischemic postconditioning in the isolated rat heart[J]. Circulation, 2004.110: III-136 [Abstract].
[45] Yang X-M P.S., Downey JM, Cohen MV. Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation[J]. Bas Res Cardiol 2005.100: 57- 63.
[46] Inagaki K B.R., Ikeno F, Mochly-Rosen D. Epsilon protein kinase C as a potential therapeutic target for the ischemic heart. [J]. Cardiovasc Res, 2006. 70(2): 222-230.
[47] Zatta A.J. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling[J]. Cardiovasc Res, 2006. 70(2): 315-324
[48] Fantinelli J.C., Mosca S.M. Comparative effects of ischemic pre and postconditioning on ischemia-reperfusion injury in spontaneously hypertensive rats (SHR)[J]. Mol Cell Biochem, 2007. 296(1-2): 45-51.
[49] Zatta A.J., Kin H., Lee G., et al. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling[J]. Cardiovasc Res, 2006. 70(2): 315-24.
[50] Inagaki K B.R., Ikeno F, Mochly-Rosen D. Cardioprotection by e-protein kinase C activation from ischemia continuous delivery and antiarrhythmic effect of an e-protein kinase C-activating peptide.[J]. Circulation 2005. 111: 44- 50.
[51] Inagaki K H.H., Dorn II GW, Mochly-Rosen D. Additive protection of the ischemic heart ex vivo by combined treatment with 6-protein kinase C inhibitor and e-protein kinase C activator[J]. Circulation, 2003.108: 869- 75.
[52] Burley D.S., Baxter G.F. Post-conditioning is dependent on PKG activiation in early reperfusion.[J]. J Mol Cell Cardiol, 2005. 38(abstract)(10): 2441-50.
[53] Hausenloy D.J., Yellon D.M. New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway[J]. Cardiovasc Res, 2004. 61(3): 448-60.
[54] Hausenloy D.J. Survival kinases in ischemic preconditioning and postconditioning[J].Cardiovasc Res, 2006. 70(2): 240-253.
[55] Bopassa J.C., Ferrera R., Gateau-Roesch O., et al. PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning[J]. Cardiovasc Res, 2006. 69(1): 178-85.
[56] Peng L.Y., Ma H., He J.G., et al. [Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart][J], Zhonghua Xin Xue Guan Bing Za Zhi, 2006. 34(8): 685-9.
[57] Mykytenko J., Reeves J.G., Kin H., et al. Persistent beneficial effect of postconditioning against infarct size: role of mitochondrial K(ATP) channels during reperfusion[J]. Basic Res Cardiol, 2008.103(5): 472-84.
[58] Schwartz L.M., Lagranha C.J. Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs[J]. Am J Physiol Heart Circ Physiol, 2006. 290(3):H1011-8.
[59] Yang X.M., Proctor J.B., Cui L., et al. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J]. J Am Coll Cardiol, 2004.44(5): 1103-10.
[60] Sun H.Y., Wang N.P., Halkos M., et al. Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways[J]. Apoptosis, 2006. 11(9): 1583-93.
[61] Suleman N., Lacerda L., Opie L.H., et al. ischemic postconditioning confers cardioprotection via phosporylation of STAT-3[J]. J Mol Cell Cardio, 2006. 40((abstract)).
[62] Gross GJ P.J. KATP channels and myocardial preconditioning: an update[J]. Am J Physiol (Heart Circ Physiol) 2003. 285: H921- 30.
[63] Simoes C S.E., Bouskela E. Effects of cromakalim and glibenclamide on arteriolar and venular diameters and macromolecular leakage in the microcirculation during ischemia/reperfusion[J]. J Cardiovasc Pharmacol, 2002(39): 340- 6.
[64] Wakiyama H C.D., Toyoda Y, Federman M, Levitsky S,McCully JD. Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis.[J]. Eur J Cardiothorac Surg, 2002. 21: 424- 33.
[65] Yao Z G.G. The ATP-dependent potassium channel: an endogenous cardioprotective mechanism[J]. J Cardiovasc Pharmacol, 1994.24(Suppl 4): 28- 34.
[66] Mykytenko J R.J., Kin H, Zatta AJ, Jiang R, Guyton RA,et al. Postconditioning reduces infarct size via mitochondrial KATP channel activation during 24 hours of reperflision. [J]. J Mol Cell Cardiol, 2005.38: 830 [Abstract].
[67] MUKHERJEE SB DM, SUDHANDIRAN G, C. S. Increase in cytosolic Ca2+ levels through the activation of non-selective cation channels induced by oxidative stress causes mitochondrial depolarization leading to apoptosis-like death in Leishmania donovani promastigotes[J]. J Biol Chem, 2002(277): 24717-27.
[68] HERZOG WR VR, SCHLOSSBERG ML, EDENBAUM LR, et al. Short-term low doseintracoronary diltiazem administered at the onset of reperfusion reduces myocardial infarct size[J]. Int J Cardiol, 1997. 59: 21 -7.
[69] Piper HM G.-D.D. Prime cause of rapid cardiomyocyte death during reperfusion[J]. Ann Thorac Surg, 1999.68:1913-9.
[70] Piper HM G.-D.D., Ovize M. A fresh look at reperfusion injury. [J]. Cardiovasc Res 1998. 38:291-300.
[71] Halestrap AP C.S., Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection[J]. Cardiovasc Res, 2004. 61: 372-85.
[72] Sun K., Liu Z.S., Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperflision injury and protective effect of ischemic postconditioning[J]. World J Gastroenterol, 2004.10(13): 1934-8.
[73] Wang H.C., Zhang H.F., Guo W.Y., et al. Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation: role of peroxynitrite formation[J]. Apoptosis, 2006.11(8): 1453-60.
[74] Di Lisa F M.R., Canton M, Barile M, Bernardi P. Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD(+) and is a causative event in the death of myocytes in postischemic reperfusion of the heart[J]. J Biol Chem 2001.276:2571-5.
[75] Griffiths EJ H.A. Protection by cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts[J]. J Mol Cell Cardiol, 1993. 25: 1461- 9.
[76] Griffiths EJ H.A. Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion[J]. Biochem J 1995.307: 93-8.
[77] Argaud L G.-R.O., Raisky O, Loufouat J, Robert D, Ovize M. Post-conditioning inhibits mitochondrial permeability transition[J]. Circulation, 2005. 111: 194- 7.
[78] Bopassa J-C F.R., Gateau-Roesch 0, Couture-Lepetit E,0vizeM. PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning[J]. Cardiovas Res, 2006. 69:178-85.
[79] Murata M., Akao M., O'Rourke B., et al. Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection[J]. Circ Res, 2001.89(10): 891-8.
[80] Kim J.S., Jin Y., Lemasters J.J. Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion[J]. Am J Physiol Heart Circ Physiol, 2006. 290(5): H2024-34.
[81] Ruiz-Meana M., Garcia-Dorado D., Miro-Casas E., et al. Mitochondrial Ca2+ uptake during simulated ischemia does not affect permeability transition pore opening upon simulated reperfusion[J]. Cardiovasc Res, 2006. 71(4): 715-24.
[82] Feng J L.E., Ahuja P, Pasch T, Perriard J-C, Zaugg M. Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3h[J]. Anesthesiology 2005.103: 987- 95.
[83] Obal D D.S., Favoccia C, Scharbatke H, Preckel B, Schlack W. The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurance in the rat in vivo[J]. Anesth Analg 2005.101: 1252- 60.
[84] Chiari PC B.M., Pagel PS, Krolikowski JG, Kersten JR, Warltier DC. Isoflurane protects against myocardial infarction during early reperfusion by activation of phosphatidylinositol-3-kinase signal transduction: evidence for anesthetic-induced postconditioning in rabbits [J]. Anesthesiology, 2005.102: 102- 9.
[85] Yang X.C., Liu Y., Wang L.F., et al. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention[J]. J Invasive Cardiol, 2007. 19(10): 424-30.
[86] Thibault H., Piot C., Ovize M. Postconditioning in man[J]. Heart Fail Rev, 2007. 12(3-4):245-8.
[2]Tullius SQ,Tilney NL.Both alloantigen-dependent and independent factors influence chronic allograft rejection[J].Transplantation,1995,59(3):313-318.
[3]Giral-Classe M,Hourmant M,Cantarovich F,et al.Contribution of prolonged emia and donor age to chronic renal allograft dysfunction[J].Am J Soc Nephrol,2000,11: 1317-1324.
[4]Wang Y,Ji HX,Xing SH,et al.SP600125,a selective JNK inhibitor,protects ischemic renal injury via suppressing the extrinsic pathways of apoptosis[J].Life Sci,2007,80(22):2067-75.
[5]Mahmoud IM,Hussein Ael A,Sarhan ME,et al.Role of combined L-arginine and prostagIandin El in renal ischemia-reperfusion injury[J].Nephron Physiol,2007,105(4):p57-65.
[6]Kaudel CP,Frink M,Schmiddem U,et al.FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia;impact on long-term survival and T-lymphocyte tissue infiltration[J].Transplant Proc,2007,39(2):499-502.
[7]Fuller TF,Rose F,Singleton KD,et al.Glutamine donor pretreatment in rat kidney transplants with severe preservation reperfusion injury[J].J Surg Res,2007,140(1):77-83.
[8]Grenz A,Eckle T,Zhang H,et al.Use of a hanging-weight system for isolated renal artery occlusion during ischemic preconditioning in mice[J].Am J Physiol Renal Physiol,2007,292(1):F475-85.
[9]Jiang SH,Liu CF,Zhang XL,et al.Renal protection by delayed ischaemic preconditioning is associated with inhibition of the inflammatory response and NF-kappaB activation[J].Cell Biochem Funct,2007,25(3):335-43.
[10]Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003,285(2):H579-88.
[11]褚薇薇,武步强,沙焕臣,et al.缺血后处理对缺血-再灌注大鼠肠黏膜的抗损伤作用[J].西安交通大学学报(医学版),2007,28(2):149-51.
[12]武步强,褚薇薇,贺国洋,et al.缺血后处理对缺血-再灌注肝脏的抗损伤作用研究[J].昆明医学院学报,2005,3:64-67.
[1]Tullius SQ,Tilney NL.Both alloantigen-dependent and independent factors influence chronic allograft rejection[J].Transplantation,1995,59(3):313-318.
[2]Giral-Classe M,Hourmant M,Cantarovich F,et al.Contribution of prolonged emia and donor age to chronic renal allograft dysfunction[J].Am J Soc Nephrol,2000,11:1317-1324.
[3]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-36.
[4]Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Cite Physiol,2003,285(2):H579-88.
[5]Kloner RA,Rezkalla SH.Preconditioning,postconditioning and their application to clinical cardiology[J].Cardiovasc Res,2006,70(2):297-307.
[6]Liu X,Chen H,Zhan B,et al.Attenuation of reperfusion injury by renal ischemic postconditioning:the role of NO[J].Biochem Biophys Res Commun,2007,359(3):628-34.
[7]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[8]chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[9]Jablonski P,Howden BO,Rae DA,et al.An experimental model for assessment of renal recovery from warm ischemia[J].Transplantation,1983,35(3):198-204.
[10]Hausenloy DJ,Yellon DM.Preconditioning and postconditioning:united at reperfusion [J].Pharmacol Yher,2007,116(2):173-91.
[11]Toosy N,McMorris EL,Grace PA,et al.Ischaemic preconditioning protects the rat kidney from reperfusion injury[J].BJU Int,1999,84(4):489-94.
[12]Hernandez DJ,Roberts WB,Miles-Thomas J,et al.Can ischemic preconditioning ameliorate renal ischemia-reperfusion injury in a single-kidney porcine model?[J].J Endourol,2008,22(11):2531:6.
[13]Timsit MO,Gadet R,Ben Abdennebi H,et al.Renal ischemic preconditioning improves recovery of kidney function and decreases alpha-smooth muscle actin expression in a rat model[J].J Urol,2008,180(1):388-91.
[14]Kin H,Zatta AJ,Lofye MT,et al.Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine[J].Cardiovasc Res,2005,67:124-33.
[15]Philipp S,Yang XM,Cui L,et al.Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade[J].Cardiovasc Res,2006,70(2):308-14.
[16]Staat P,Rioufol G,Piot C,et al.Postconditioning the human heart[J].Circulation,2005,112(14):2143-8.
[17]Sun K,Liu ZS,Sun Q.Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning[J].World J Gastroenterol,2004,10(13):1934-8.
[18]Zhao H,Sapolsky RM,Steinberg GK.Interrupting reperfusion as a stroke therapy:ischemic postconditioning reduces infarct size after focal ischemia in rats[J].J Cereb Blood Flow Metab,2006,26(9):1114-21.
[1]Wang HC,Zhang HF,Guo WY,et al.Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation:role of peroxynitrite formation[J].Apoptosis,2006,11(8):1453-60.
[2]Wang C,Neff DA,Krolikowski JG,et al.The influence of B-cell lymphoma 2 protein,an antiapoptotic regulator of mitochondrial permeability transition,on isoflurane-induced and ischemic postconditioning in rabbits[J].Anesth Analg,2006,102(5):1355-60.
[3]Loukogeorgakis SP,Panagiotidou AT,Yellon DM,et al.Postconditioning protects against endothelial ischemia-reperfusion injury in the human forearm[J].Circulation,2006, 113(7):1015-9.
[4]Tsang A,Hausenloy DJ,Mocanu MM,et al.Postconditioning:a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway[J].Circ Res,2004,95(3):230-2.
[5]Philipp S,Yang XM,Cui L,et al.Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade[J].Cardiovasc Res,2006,70(2):308-14.
[6]Ovize M.[Postconditioning:lethal reperfusion injury as a therapeutic target][J].Ann Cardiol Angeiol(Paris),2006,55(2):66-9.
[7]陈主初,郭恒怡,王树人.缺血-再灌注损伤.病理生理学.2005.191-201.
[8]Sun HY,Wang NP,Kerendi F,et al.Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload[J].Am J Physiol Heart Circ Physiol,2005,288(4):H1900-8.
[9]Vinten-Johansen J,Zhao ZQ,Zatta AJ,et al.Postconditioning--A new link in nature's armor against myocardial ischemia-reperfusion injury[J].Basic Res Cardiol,2005,100(4):295-310.
[10]Sun K,Liu ZS,Sun Q.Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning[J].World J Gastroenterol,2004,10(13):1934-8.
[11]Dosenko VE,Nagibin VS,Tumanovskaya LV,et al.Postconditioning prevents apoptotic necrotic and autophagic cardiomyocyte cell death in culture[J].Fiziol Zh,2005,51(3):12-7.
[12]Singh D,Kaur R,Chander V,et al.Antioxidants in the prevention of renal disease[J].J Med Food,2006,9(4):443-50.
[13]Yamanobe T,Okada F,Iuchi Y,et al.Deterioration of ischemia/reperfusion-induced acute renal failure in SOD1-defcient mice[J].Free Radic Res,2007,41(2):200-7.
[14]Zima AV,Blatter LA.Redox regulation of cardiac calcium channels and transporters[J].Cardiovasc Res,2006,71(2):310-21.
[15]Wang YH,Wang WY,Chang CC,et al.Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation[J].J Biomed Sci,2006,13(1):127-41.
[16]Johnson KJ,Weinberg JM.Postischemic renal injury due to oxygen radicals[J].Curr Opin Nephrol Hypertens,1993,2(4):625-35.
[17]Dobashi K,Ghosh B,Orak JK,et al.Kidney ischemia-reperfusion:modulation of antioxidant defenses[J].Mol Cell Biochem,2000,205(1-2):1-11.
[18]Singla DK,Kaur K,Sharma AK,et al.Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injury[J].Can J Physiol Pharmacol,2007,85(3-4):439-43.
[19]Ellis EM.Reactive carbonyls and oxidative stress:potential for therapeutic intervention [J].Pharmacol Ther,2007,115(1):13-24.
[20]Lee WY,Lee JS,Lee SM.Protective effects of combined ischemic preconditioning and ascorbic acid on mitochondrial injury in hepatic ischemia/reperfusion[J].J Surg Res,2007,142(1):45-52.
[21]Kotani Y,Ishino K,Osaki S,et al.Efficacy of MCI-186,a free-radical scavenger and antioxidant,for resuscitation of nonbeating donor hearts[J].J Thorac Cardiovasc Surg,2007,133(6):1626-32.
[22]Lee WY,Lee SM.Ischemic preconditioning protects post-ischemic oxidative damage to mitochondria in rat liver[J].Shock,2005,24(4):370-5.
[23]Penna C RR,Mancardi D,Raimondo D,Cappello S,,Gattullo D ea.Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism,mitochondrial ATP sensitive K+channel and protein kinase C activation[J].Bas Res Cardiol,2006,101(2):180-189.
[24]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[25]Chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[26]Aydin A,Orhan H,Sayal A,et al.Oxidative stress and nitric oxide related parameters in type Ⅱ diabetes mellitus:effects of glycemic control[J].Clin Biochem,2001,34(1):65-70.
[27]Kerimova AA,Atalay M,Yusifov EY,et al.Antioxidant enzymes;possible mechanism of gold compound treatment in rheumatoid arthritis[J].Pathophysiology,2000,7(3):209-213.
[28]Chen H,Xing B,Liu X,et al.Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury[J].Eur J Pharmacol,2008,581(3):306-14.
[29]Chien CT,Chen CF,Hsu SM,et al.Protective mechanism of preconditioning hypoxia attenuates apoptosis formation during renal ischemia/reperfusion phase[J].Transplant Proc,1999,31(5):2012-3.
[30]Hansen JM,Choe HS,Carney EW,et al.Differential antioxidant enzyme activities and glutathione content between rat and rabbit conceptuses[J].Free Radic Biol Med,2001,30(10):1078-88.
[31]Ugochukwu NH,Cobourne MK.Modification of renal oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with extracts from Gongronema latifolium leaves[J].Clin Chim Acta,2003,336(1-2):73-81.
[32]Ohkawa H,Ohishi N,Yagi K.Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction[J].Anal Biochem,1979,95(2):351-8.
[33]Rubinstein I,Abassi Z,Milman F;et al.Hyperbaric oxygen treatment improves GFR in rats with ischaemia/reperfusion renal injury:a possible role for the antioxidant/oxidant balance in the ischaemic kidney[J].Nephrol Dial Transplant,2009,24(2):428-36.
[34]Tenorio-Velazquez VM,Barrera D,Franco M,et al.Hypothyroidism attenuates protein tyrosine nitration,oxidative stress and renal damage induced by ischemia and reperfusion:effect unrelated to antioxidant enzymes activities[J].BMC Nephrol,2005,6:12.
[35]Kaur H,Padi SS,Chopra K.Attenuation of renal ischemia-reperfusion injury by trimetazidine:evidence of an in vivo antioxidant effect[J].Methods Find Exp Clin Pharmacol,2003,25(10):803-9.
[36]Zurovsky Y,Eligal Z,Grossman S.Unilateral renal ischemia reperfusion in the rat:effect of blood volume trapped in the kidney,sucrose infusion,and antioxidant treatments[J].Exp Toxicol Pathol,1995,47(6):471-8.
[1]Vinten-Johansen J,Zhao ZQ,Zatta AJ,et al.Postconditioning-A new link in nature's armor against myocardial ischemia-reperfusion injury[J].Basic Res Cardiol,2005,100(4):295-310.
[2]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[3]Chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[4]Sadis C,Teske G,Stokman G,et al.Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway[J].PLoS ONE,2007,2(5):e469.
[5]Roelofs JJ,Rouschop KM,Leemans JC,et al.Tissue-type plasminogen activator modulates inflammatory responses and renal function in ischemia reperfusion injury[J].J Am Soc Nephrol,2006,17(1):131-40.
[6]Miura M,Fu X,Zhang QW,et al.Neutralization of Gro alpha and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury[J].Am J Pathol,2001,159(6):2137-45.
[7]Carden DL,Smith JK,Korthuis RJ.Neutrophil-mediated microvascular dysfunction in postischemic canine skeletal muscle.Role of granulocyte adherence[J].Circ Res,1990,66(5):1436-44.
[8]Furuichi K,Gao JL,Horuk R,et al.Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia-reperfusion injury[J].J Immunol,2008,181(12):8670-6.
[9]Kin H,Zhao ZQ,Sun HY,et al.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J].Cardiovasc Res,2004,62(1):74-85.
[10]Okusa MD.The inflammatory cascade in acute ischemic reperfussion renal failure[J].Nephron Exp Nephrol,2002,90:133-138.
[11]Ross R.Mechanism of disease:atherosclerosis,an inflammatory disease[J].New Engl J Med,1999,340:115-21.
[12]Sinisalo J,Paronen J,Mattila K,et al.Relation of inflammation to vascular function in patients with coronary heart disease[J].Atherosclerosis,1999,149(403-11).
[13]Hausknecht B,Voelkl S,Riess R,et al.Expression of cyclooxygenase-2 in biopsies obtained from human transplanted kidneys undergoing rejection[J].Transplantation,2003,76:109-14.
[14]Carla Q F,Niels O.S.Cm,He'lady S.P,et al.Cyclooxygenase 1 and/or 2 blockade ameliorates the renal tissue damage triggered by ischemia and reperfusion injury[J]. International Immunopharmacology 2005,5:79-84.
[15]Feitoza CQ,Camara NO,Pinheiro HS,et al.Cyclooxygenase 1 and/or 2 blockade ameliorates the renal tissue damage triggered by ischemia and reperfusion injury[J].Int Immunopharmacol,2005,5(1):79-84.
[16]Matsuyama M,Yoshimura R,Hase T,et al.Study of cyclooxygenase-2 in renal ischemia-reperfusion injury[J].Transplant Proc,2005,37(1):370-2.
[17]Chan CC,Rodger IW.Selective cyclooxygenase-2 inhibitors as potential therapeutic agents for inflammatory diseases[J].Adv Exp Med Biol,1997,407:157-61.
[1]Lopez-Neblina F,Toledo AH,Toledo-Pereyra LH.Molecular biology of apoptosis in ischemia and reperfusion[J].J Invest Surg,2005,18(6):335-50.
[2]Padanilam BJ.Cell death induced by acute renal injury:a perspective on the contributions of apoptosis and necrosis[J].Am J Physiol Renal Physiol,2003,284(4):F608-27.
[3]Tsujimoto Y.Cell death regulation by the Bcl-2 protein family in the mitochondria[J].J Cell Physiol,2003,195(2):158-67.
[4]Cochrane J,Williams BT,Banerjee A,et al.Ischemic preconditioning attenuates functional,metabolic,and morphologic injury from ischemic acute renal failure in the rat [J].Ren Fail,1999,21(2):135-45.
[5]Chen H,Xing B,Liu X,et al.Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat[J].Transpl Int,2008,21(4):364-71.
[6]Liu X,Chen H,Zhan B,et al.Attenuation of reperfusion injury by renal ischemic postconditioning:the role of NO[J].Biochem Biophys Res Commun,2007,359(3):628-34.
[7]Kher A,Meldrum KK,Hile KL,et al.Aprotinin improves kidney function and decreases tubular cell apoptosis and proapoptotic signaling after renal ischemia-reperfusion[J].J Thorac Cardiovasc Surg,2005,130(3):662-9.
[8]Kishino M,Yukawa K,Hoshino K,et al.Deletion of the kinase domain in death-associated protein kinase attenuates tubular cell apoptosis in renal ischemia-reperfusion injury[J].J Am Soc Nephrol,2004,15(7):1826-34.
[9]Hou Q,Cymbalyuk E,Hsu SC,et al.Apoptosis modulatory activities of transiently expressed Bcl-2:roles in cytochrome C release and Bax regulation[J].Apoptosis,2003,8(6):617-29.
[10]Saito M,Korsmeyer SJ,Schlesinger PH.BAX-dependent transport of cytochrome c reconstituted in pure liposomes[J].Nat Cell Biol,2000,2(8):553-5.
[11]Willis SN,Adams JM.Life in the balance:how BH3-only proteins induce apoptosis[J].Curr Opin Cell Biol,2005,17(6):617-25.
[12]Dejean LM,Martinez-Caballero S,Manon S,et al.Regulation of the mitochondrial apoptosis-induced channel,MAC,by BCL-2 family proteins[J].Biochim Biophys Acta,2006,1762(2):191-201.
[13]Vlahakis SR,Badley AD.Influence of proteasome inhibitors on apoptosis[J].Curr Opin Clin Nutr Metab Care,2006,9(1):42-7.
[14]Scarabelli TM,Knight R,Stephanou A,et al.Clinical implications of apoptosis in ischemic myocardium[J].Curr Probl Cardiol,2006,31(3):181-264.
[15]Oakes SA,Lin SS,Bassik MC.The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins[J].Curr Mol Med,2006,6(1):99-109.
[16]Chen H,Xing B,Liu X,et al.Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury[J].Eur J Pharmacol,2008,581(3):306-14.
[17]Yokozawa T,Chen CP,Rhyu DY,et al.Potential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo[J].Nephron,2002,92(1):133-41.
[18]Vinten-Johansen J,Zhao ZQ,Zatta AJ,et al.Postconditioning-A new link in nature's armor against myocardial ischemia-reperfusion injury[J].Basic Res Cardiol,2005,100(4):295-310.
[19]褚薇薇.缺血后处理抗大鼠肠缺血-再灌拄损伤的作用及其机制研究[J].昆明医学 院博士学位论文,2007:75-82.
[20]Kerr JF,Wyllie AH,Currie AR.Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics[J].Br J Cancer,1972,26(4):239-57.
[21]Majno G;Joris I.Apoptosis,oncosis,and necrosis.An overview of cell death[J].Am J Pathol,1995,146(1):3-15.
[22]Li Y,Chopp M,Jiang N,et al.Induction of DNA fragmentation after 10 to 120 minutes of focal cerebral ischemia in rats[J].Stroke,1995,26(7):1252-7;discussion 1257-8.
[23]Kohli V,Selzner M,Madden JF,et al.Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver[J].Transplantation,1999,67(8):1099-105.
[24]Fliss H.Accelerated apoptosis in reperfused myocardium:friend of foe?[J].Basic Res Cardiol,1998,93(2):90-3.
[25]门秀丽,张连元,董淑云.牛磺酸对大鼠肢体缺血再灌注肺损伤时细胞凋亡的影响.[J].中国病理生理杂志,2004,20(3):4212-41.
[26]李彬,温笠,杨新东.大鼠肢体缺血再灌注损伤后细胞凋亡与Bcl-2和Bax蛋白表达的关系[J].温州医学院学报,2003,23(10):3012-3031.
[1]Zhao Z.Q.,Corvera J.S.,Halkos M.E.,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003.285(2):H579-88.
[2]Philipp S.,Critz S.D.,Cui L.,et al.Localizing extracellular signal-regulated kinase(ERK) in pharmacological preconditioning's trigger pathway[J].Basic Res Cardiol,2006.101(2):159-67.
[3]Darling C.E.,Jiang R.,Maynard M.,et al.Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts:role of ERK1/2[J].Am J Physiol Heart Circ Physiol,2005.289(4):H1618-26.
[4]van Vuuren D.,Genis A.,Genade S.,et al.Postconditioning the isolated working rat heart[J].Cardiovasc Drugs Ther,2008.22(5):391-7.
[5]Penna C.,Mancardi D.,Rastaldo R.,et al.Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling[J].Cardiovasc Res,2007.75(1):168-77.
[6]Staat R,Rioufol G.,Piot C.,et al.Postconditioning the human heart[J].Circulation,2005.112(14):2143-8.
[7]Darling C.E.,Solari P.B.,Smith C.S.,et al.'Postconditioning' the human heart:multiple balloon inflations during primary angioplasty may confer cardioprotection[J].Basic Res Cardiol,2007.102(3):274-8.
[8] Opie L.H. Cardiologists are living through exciting times. The example of postconditioning to protect the human heart during revascularization[J]. Ann Cardiol Angeiol (Paris), 2006. 55(2): 64-5.
[9] Kin H., Zhao Z.Q., Sun H.Y., et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J]. Cardiovasc Res, 2004.62(1): 74-85.
[10] Yang X-M P.J., Cui L, Krieg T, Downey JM, Cohen MV. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J]. J Am Coll Cardiol, 2004. 44: 1103-10.
[11] Philipp SD D J., Cohen MV. Postconditioning must be initiated in less than lminute following reperfusion and is dependent on adenosine receptors and P13-kinase.[J]. Circulation 2004.110:III-168 [Abstract].
[12] Halkos M.E., Kerendi F., Corvera J.S., et al. Myocardial protection with postconditioning is not enhanced by ischemic preconditioning[J]. Ann Thorac Surg, 2004. 78(3): 961-9; discussion 969.
[13] Tsang A., Hausenloy D.J., Mocanu M.M., et al. Postconditioning: a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway[J]. Circ Res, 2004. 95(3): 230-2.
[14] Bolli R. Oxygen-derived free radicals and myocardial reperfusion injury: an overview[J]. Cardiovasc Drugs Ther, 1991. 5(Suppl 2): 249- 68.
[15] Lucches B.R. Complement, neutrophils and free radicals: mediators of reperfusion injury[J]. Arzneim-Forsch/Drug Res, 1994. 44: 420-32.
[16] Jeroudi M.O. H.C.J., Bolli R. Myocardial reperfusion injury: role of oxygen radicals and potential therapy with antioxidants[J]. Am J Cardiol, 1994. 73: 2B-7B.
[17] Herkert O D.I., Brandes RP, Hess J, Busse R, Gorlach A, . NADPH oxidase mediates tissue factor-dependent surface procoagulant activity by thrombin in human vascular smooth muscle cells[J]. Circulation, 2002.105: 2030- 6.
[18] Duilio C A.G, Kuppusamy P, DiPaula A, Becker LC, Zweier, JL. Neutrophils are primary source of O_2 radicals during reperfusion after prolonged myocardial ischemia[J]. Am J Physiol (Heart Circ Physiol), 2001. 280: H2649- 57.
[19] Vinten-Johansen J. Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury[J]. Cardiovasc Res, 2004. 61:481-97.
[20] Sun H.Y., Wang N.P., Kerendi E, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload[J]. Am J Physiol Heart Circ Physiol,2005. 288(4):H1900-8.
[21] Serviddio G, Di Venosa N., Federici A., et al. Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia-reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion[J], Faseb J, 2005.19(3): 354-61.
[22] PENNA C.R., MANCARDI D., RAIMGNDO D., et al. Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP sensitive K+channel and protein kinase C activation[J]. Bas Res Cardiol, 2006. 101(2):180-189.
[23] Downey J.M., Cohen M.V. A really radical observation-a comment on Penna et al. in Basic Res Cardiol (2006) 101:180-189[J]. Basic Res Cardiol, 2006.101(2): 190-1.
[24] Yang X.M., Philipp S., Downey J.M., et al. Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation[J]. Basic Res Cardiol, 2005.100(1): 57-63.
[25] Philipp S., Yang X.M., Cui L., et al. Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade[J]. Cardiovasc Res, 2006. 70(2): 308-14.
[26] Kin H., Zatta A.J., Lofye M.T., et al. Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine[J]. Cardiovasc Res, 2005. 67: 124-33.
[27] Kilpatrick EL N.P., Mentzer Jr RM, Lasley RD. Adenosine A3 agonist cardioprotection in isolated rat and rabbit hearts is blocked by the Al antagonist DPCPX[J]. Am J Physiol 2001. 281:H847-53.
[28] Jang Y., Xi J., Wang H., et al. Postconditioning prevents reperfusion injury by activating delta-opioid receptors[J]. Anesthesiology, 2008.108(2): 243-50.
[29] Zatta A.J., Kin H., Yoshishige D., et al. Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation[J]. Am J Physiol Heart Circ Physiol, 2008. 294(3): H1444-51.
[30] Wang J., Gao Q., Shen J., et al. [Kappa-opioid receptor mediates the cardioprotective effect of ischemic postconditioning][J]. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2007.36(1): 41-7.
[31] Zhao Z.-Q., SH-Y, Wang N.-P., et al. Hypoxic postconditioning attenuates cardiomyocyte apoptosis via inhibition of jnk and p38 kinases pathway[J]. J Mol Cell Cardiol, 2005. 38: 870.
[32] YANG X.M, DOWNEY J.M., COHEN M.V. Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation[J]. Bas Res Cardiol 2005.100: 57- 63.
[33] Zhao Z-Q S.H.-Y., Wang N-P, Kin H, Guyton RA, Vinten-Johansen J. Hypoxic postconditioning attenuates cardiomyocyte apoptosis via inhibition of jnk and p38 kinases pathway[J]. J Mol Cell Cardiol, 2005. 38: 870[Abstract].
[34] Mackman N. The role of the tissue factor-thrombin pathway in cardiac ischemia- reperfusion injury[J]. Semin Vasc Med 2003. 3: 193-8.
[35] Jobe L.J., Jiang R., Wang N.-P., et al. Tissue factor, factors Vila and Xa expression and local generation of thrombin in at risk myocardium occurs specifically during reperfusion[J]. Circulation, 2004.110(111-297).
[36] Jiang R.J., Mykytenko J., Zatta A.J., et al. Postconditioning reduces reperfusion injury by inhibiting the tissue factor-thrombin pathway in a closed-chest porcine model of ischemia- reperfusion [J]. Circulation, 2005.112(Suppl II): II-309[Abstract].
[37] Vinten-Johansen J Z.Z.-Q., Nakamura M, Jordan JE, Ronson RS,, Thourani VH e.a. Nitric oxide and the vascular endothelium in myocardial ischemia- reperfusion injurya. [J]. In: Das DKHeart in Stress 1999. 874:354-70.
[38] Lefer DJ N.K., Vinten-Johansen J, Ma X-L, Lefer AM. Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs[J]. Am J Physiol 1992. 263: H850- 6.
[39] Tsao PS A.N., Lefer DJ, Johnson III G, Lefer AM. . Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat[J]. Circulation, 1990. 82: 1402-12.
[40] Wang P Z.J. Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitritemediated reperfusion injury. [J]. J Biol Chem, 1996. 271:29223- 30.
[41] Johnson III G T.P., Lefer AM. Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion[J]. Crit Care Med, 1991.19:244- 52.
[42] Lefer DJ N.K., Johnston WE, Vinten-Johansen J. Antineutrophil and myocardial protecting action of SPM-5185, a novel nitric oxide (NO) donor, following acute myocardial ischemia . and reperfusion in dogs[J]. Circulation, 1993. 88:2337- 50.
[43] Cohen M.V. Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies.[J]. Cardiovasc Res, 2006. 70(2): 231-239
[44] Pagliaro P.R. R.R., Penna C, Mancardi D, Cappello S, Losano Gattullo D, et al. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway is involved in ischemic postconditioning in the isolated rat heart[J]. Circulation, 2004.110: III-136 [Abstract].
[45] Yang X-M P.S., Downey JM, Cohen MV. Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation[J]. Bas Res Cardiol 2005.100: 57- 63.
[46] Inagaki K B.R., Ikeno F, Mochly-Rosen D. Epsilon protein kinase C as a potential therapeutic target for the ischemic heart. [J]. Cardiovasc Res, 2006. 70(2): 222-230.
[47] Zatta A.J. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling[J]. Cardiovasc Res, 2006. 70(2): 315-324
[48] Fantinelli J.C., Mosca S.M. Comparative effects of ischemic pre and postconditioning on ischemia-reperfusion injury in spontaneously hypertensive rats (SHR)[J]. Mol Cell Biochem, 2007. 296(1-2): 45-51.
[49] Zatta A.J., Kin H., Lee G., et al. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling[J]. Cardiovasc Res, 2006. 70(2): 315-24.
[50] Inagaki K B.R., Ikeno F, Mochly-Rosen D. Cardioprotection by e-protein kinase C activation from ischemia continuous delivery and antiarrhythmic effect of an e-protein kinase C-activating peptide.[J]. Circulation 2005. 111: 44- 50.
[51] Inagaki K H.H., Dorn II GW, Mochly-Rosen D. Additive protection of the ischemic heart ex vivo by combined treatment with 6-protein kinase C inhibitor and e-protein kinase C activator[J]. Circulation, 2003.108: 869- 75.
[52] Burley D.S., Baxter G.F. Post-conditioning is dependent on PKG activiation in early reperfusion.[J]. J Mol Cell Cardiol, 2005. 38(abstract)(10): 2441-50.
[53] Hausenloy D.J., Yellon D.M. New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway[J]. Cardiovasc Res, 2004. 61(3): 448-60.
[54] Hausenloy D.J. Survival kinases in ischemic preconditioning and postconditioning[J].Cardiovasc Res, 2006. 70(2): 240-253.
[55] Bopassa J.C., Ferrera R., Gateau-Roesch O., et al. PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning[J]. Cardiovasc Res, 2006. 69(1): 178-85.
[56] Peng L.Y., Ma H., He J.G., et al. [Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart][J], Zhonghua Xin Xue Guan Bing Za Zhi, 2006. 34(8): 685-9.
[57] Mykytenko J., Reeves J.G., Kin H., et al. Persistent beneficial effect of postconditioning against infarct size: role of mitochondrial K(ATP) channels during reperfusion[J]. Basic Res Cardiol, 2008.103(5): 472-84.
[58] Schwartz L.M., Lagranha C.J. Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs[J]. Am J Physiol Heart Circ Physiol, 2006. 290(3):H1011-8.
[59] Yang X.M., Proctor J.B., Cui L., et al. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J]. J Am Coll Cardiol, 2004.44(5): 1103-10.
[60] Sun H.Y., Wang N.P., Halkos M., et al. Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways[J]. Apoptosis, 2006. 11(9): 1583-93.
[61] Suleman N., Lacerda L., Opie L.H., et al. ischemic postconditioning confers cardioprotection via phosporylation of STAT-3[J]. J Mol Cell Cardio, 2006. 40((abstract)).
[62] Gross GJ P.J. KATP channels and myocardial preconditioning: an update[J]. Am J Physiol (Heart Circ Physiol) 2003. 285: H921- 30.
[63] Simoes C S.E., Bouskela E. Effects of cromakalim and glibenclamide on arteriolar and venular diameters and macromolecular leakage in the microcirculation during ischemia/reperfusion[J]. J Cardiovasc Pharmacol, 2002(39): 340- 6.
[64] Wakiyama H C.D., Toyoda Y, Federman M, Levitsky S,McCully JD. Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis.[J]. Eur J Cardiothorac Surg, 2002. 21: 424- 33.
[65] Yao Z G.G. The ATP-dependent potassium channel: an endogenous cardioprotective mechanism[J]. J Cardiovasc Pharmacol, 1994.24(Suppl 4): 28- 34.
[66] Mykytenko J R.J., Kin H, Zatta AJ, Jiang R, Guyton RA,et al. Postconditioning reduces infarct size via mitochondrial KATP channel activation during 24 hours of reperflision. [J]. J Mol Cell Cardiol, 2005.38: 830 [Abstract].
[67] MUKHERJEE SB DM, SUDHANDIRAN G, C. S. Increase in cytosolic Ca2+ levels through the activation of non-selective cation channels induced by oxidative stress causes mitochondrial depolarization leading to apoptosis-like death in Leishmania donovani promastigotes[J]. J Biol Chem, 2002(277): 24717-27.
[68] HERZOG WR VR, SCHLOSSBERG ML, EDENBAUM LR, et al. Short-term low doseintracoronary diltiazem administered at the onset of reperfusion reduces myocardial infarct size[J]. Int J Cardiol, 1997. 59: 21 -7.
[69] Piper HM G.-D.D. Prime cause of rapid cardiomyocyte death during reperfusion[J]. Ann Thorac Surg, 1999.68:1913-9.
[70] Piper HM G.-D.D., Ovize M. A fresh look at reperfusion injury. [J]. Cardiovasc Res 1998. 38:291-300.
[71] Halestrap AP C.S., Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection[J]. Cardiovasc Res, 2004. 61: 372-85.
[72] Sun K., Liu Z.S., Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperflision injury and protective effect of ischemic postconditioning[J]. World J Gastroenterol, 2004.10(13): 1934-8.
[73] Wang H.C., Zhang H.F., Guo W.Y., et al. Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation: role of peroxynitrite formation[J]. Apoptosis, 2006.11(8): 1453-60.
[74] Di Lisa F M.R., Canton M, Barile M, Bernardi P. Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD(+) and is a causative event in the death of myocytes in postischemic reperfusion of the heart[J]. J Biol Chem 2001.276:2571-5.
[75] Griffiths EJ H.A. Protection by cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts[J]. J Mol Cell Cardiol, 1993. 25: 1461- 9.
[76] Griffiths EJ H.A. Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion[J]. Biochem J 1995.307: 93-8.
[77] Argaud L G.-R.O., Raisky O, Loufouat J, Robert D, Ovize M. Post-conditioning inhibits mitochondrial permeability transition[J]. Circulation, 2005. 111: 194- 7.
[78] Bopassa J-C F.R., Gateau-Roesch 0, Couture-Lepetit E,0vizeM. PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning[J]. Cardiovas Res, 2006. 69:178-85.
[79] Murata M., Akao M., O'Rourke B., et al. Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection[J]. Circ Res, 2001.89(10): 891-8.
[80] Kim J.S., Jin Y., Lemasters J.J. Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion[J]. Am J Physiol Heart Circ Physiol, 2006. 290(5): H2024-34.
[81] Ruiz-Meana M., Garcia-Dorado D., Miro-Casas E., et al. Mitochondrial Ca2+ uptake during simulated ischemia does not affect permeability transition pore opening upon simulated reperfusion[J]. Cardiovasc Res, 2006. 71(4): 715-24.
[82] Feng J L.E., Ahuja P, Pasch T, Perriard J-C, Zaugg M. Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3h[J]. Anesthesiology 2005.103: 987- 95.
[83] Obal D D.S., Favoccia C, Scharbatke H, Preckel B, Schlack W. The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurance in the rat in vivo[J]. Anesth Analg 2005.101: 1252- 60.
[84] Chiari PC B.M., Pagel PS, Krolikowski JG, Kersten JR, Warltier DC. Isoflurane protects against myocardial infarction during early reperfusion by activation of phosphatidylinositol-3-kinase signal transduction: evidence for anesthetic-induced postconditioning in rabbits [J]. Anesthesiology, 2005.102: 102- 9.
[85] Yang X.C., Liu Y., Wang L.F., et al. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention[J]. J Invasive Cardiol, 2007. 19(10): 424-30.
[86] Thibault H., Piot C., Ovize M. Postconditioning in man[J]. Heart Fail Rev, 2007. 12(3-4):245-8.