抑制COX-2与5-LOX途径对大鼠肝脏缺血再灌注损伤的影响
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摘要
目的:探讨环氧合酶-2(cyclooxygenase-2、COX-2)抑制剂塞来昔布和5-脂氧合酶(5-lipoxygenase,5-LOX)抑制剂MK-886对大鼠肝脏缺血再灌注损伤的影响。
方法:成年雄性健康SD大鼠50只,随机数字表法分为5组:正常组(B1)、缺血再灌注组(B2)、COX-2抑制剂治疗组(B3)、5-LOX抑制剂治疗组(B4)、联合治疗组(B5),每组10只。制作大鼠肝脏缺血再灌注模型,夹闭肝脏血管30分钟致缺血,再灌注后不同时点(术后30分钟,术后60分钟)处死大鼠,抽取下腔静脉血并留取肝脏组织(肝左叶)保存待检测。一步法逆转录-聚合酶链式反应RT-PCR检测各组肝组织中COX-2 mRNA及5-LOX mRNA的表达;流式细胞术检测肝细胞凋亡率,;肝组织切片HE染色光镜下观察肝细胞变性、坏死等改变的情况,确定组织损伤程度并统计:血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移(aspartate aminotransferase,AST)检测肝功能变化。
结果:
1.RT-PCR:再灌注后各时点B2组中COX-2 mRNA及5-LOX mRNA的表达水平均明显高于B1组(P＜0.05);再灌注后30min,B2,B3,B4及B5组间数据无统计学差异(P＞0.05);再灌注后1h,塞来昔布干预组(B3)COX-2 mRNA的表达水平较B2下调,而5-LOX mRNA的表达量较B2组明显升高(P＜0.05);B4组给予MK-886后5-LOX的mRNA表达与B2组比较明显下调(P＜0.05),而COX-2的mRNA表达与B2比较无统计学差异(P＞0.05);两种药物联合作用后COX-2和5-LOX的mRNA表达较B2组均下调(P＜0.05)
2.凋亡:通过流式细胞术分析肝细胞凋亡率显示,与B2组相比,各时点B3,B4,B5组的肝细胞凋亡率显著下降(P＜0.05);B5组凋亡率较B3,B4组明显下降(P＜0.05);而B3组与B4组之间肝细胞凋亡率无显著性差异(P＞0.05)。
3.血清AST、ALT:再灌注后各时点B2组中血清AST、ALT明显高于B1组(P＜0.05);B5组数据明显低于B2组(P＜0.05);B3,B4组血清AST、ALT水平低于B2组,但无统计学差异(P＞0.05)。
4.HE染色:与B1组相比,B2组肝组织改变明显;B3,B4及B5组较B2组肝组织改变减轻;B5组病理学损伤较B3,B4更轻。
结论:COX-2抑制剂塞来昔布及5-LOX抑制剂MK-886减轻肝细胞凋亡,对大鼠肝脏缺血再灌注起保护作用;单独作用肝脏缺血再灌注后,两药之间比较,作用无明显差异;两种药物联合作用COX-2与5-LOX两条通路能更有效的减轻大鼠肝脏缺血再灌注损伤。
Objective:Test the efficacy of the selective COX-2 inhibitor celecoxib、5-LOX inhibitor MK-886 or their combination on hepatic ischemia-reperfusion injury in rat,and to investigate whether the dual inhibition of COX-2 and 5-LOX has a more power protective effect than single inhibition of either COX-2 or 5-LOX alone on hepatic ischemia-reperfusion injury in rat.
Method:Fifty male SD rats were randomly divided into 5 groups:sham-operated control group(B1)、liver ischemia-reperfusion group(B2)、Celecoxib and liver IR group(B3)、MK-886 and liver IR group(B4)、Celecoxib+ MK-886 and liver IR group(B5).Establish a rat model of hepatic ischemia-reperfusion,30 min of total hepatic vascular occlusion and then 30min or 60 min reperfusion were performed to animals in groups B2,B3,B4 and B5.The left hepatic lobes and blood sample which were obtained from the inferior cava vena were taken at 0.5h and 1h after reperfusion.;One step-RT-PCR was used to detect the expressions of COX-2 and 5-LOX;The apoptosis rate of the hepatocytes were detected by flow cytometry.; Hematoxylin Eosin staining was used to classify the injury extent of every samples; Alanine aminotransferase(ALT),aspartate aminotransferase(AST) as well as hepatic histopathological changes were measured;
Result:
1.RT-PCR:The expressions of COX-2 mRNA and 5-LOX mRNA in B2 group was significantly higher compared with the B1 group in different time after reperfusion(P＜0.05);The difference did not reach a statistically significant level in the B3,B4 and B5 groups compared with the B2 group at 30min after reperfusion (P＞0.05);The expressions of COX-2 mRNA was lower in COX-2 inhibitor preconditioning in B3 group than the B2 group at 1h after reperfusion,meanwhile,the expressions of 5-LOX mRNA was significantly higher compared with the B2 group (P＜0.05);The expression of 5-LOX mRNA in the B4 group which was treated with MK-886 was significantly lower than in the B2 group at 1h after reperfusion(P＜0.05), meanwhile,MK-886 had not effect on the expression of the Cox-2(p＞0.05);The expressions of Cox-2 mRNA and 5-lox mRNA in the B5 which were treated with the combination of celecoxib and MK-886 were lower than B2 group at 1h after reperfusion(p＜0.01)
2.Apoptosistic:Analysis of apoptosis by the flow cytometry method showed that the apoptosis rate of the hepatocytes decreased significantly in the B3,B4 and B5 groups compared with the B2 group(P＜0.05);The data of the B5 group was significantly lower than the B3 and B4 groups(P＜0.05);There was no difference in the decline in the apoptosis rate of the hepatocytes between the B3 and B4 groups(P＞0.05).
3.The levels of AST and ALT in blood serum:The datas of B2 group was significantly higher compared with B1 group in different time after reperfusion (P＜0.05);The dates of the B5 group was significantly lower than the B2 group(P＜0.05);The dates of the B3 and B4 groups was lower than the B2 group, which had no significant difference(P＞0.05);The dates of the B5 group was lower than the B3 and B4 groups,but the difference did not reach a statistically significant level(P＞0.05).
4.HE stain:Compared with B1 group,B2 group showed great changes.The pathological lesions were lighter in B3,B4 and B5groups than in B2 group.The pathological lesions were lighter in B5 group than in B3 and B4 group.
Conclusion:COX-2 inhibitor Celecoxib and 5-LOX inhibitor MK-886 were found to be effective in prevention of liver injury by reducing apoptosis in a hepatic I/R model. The efficacy was no different between the celecoxib and MK-886 pretreated groupson hepatic ischemia-reperfusion injury in rat.The dual inhibition of COX-2 and 5-LOX may present a superior protective effect than single inhibition of either COX-2 or 5-LOX alone.
方法:成年雄性健康SD大鼠50只,随机数字表法分为5组:正常组(B1)、缺血再灌注组(B2)、COX-2抑制剂治疗组(B3)、5-LOX抑制剂治疗组(B4)、联合治疗组(B5),每组10只。制作大鼠肝脏缺血再灌注模型,夹闭肝脏血管30分钟致缺血,再灌注后不同时点(术后30分钟,术后60分钟)处死大鼠,抽取下腔静脉血并留取肝脏组织(肝左叶)保存待检测。一步法逆转录-聚合酶链式反应RT-PCR检测各组肝组织中COX-2 mRNA及5-LOX mRNA的表达;流式细胞术检测肝细胞凋亡率,;肝组织切片HE染色光镜下观察肝细胞变性、坏死等改变的情况,确定组织损伤程度并统计:血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移(aspartate aminotransferase,AST)检测肝功能变化。
结果:
1.RT-PCR:再灌注后各时点B2组中COX-2 mRNA及5-LOX mRNA的表达水平均明显高于B1组(P＜0.05);再灌注后30min,B2,B3,B4及B5组间数据无统计学差异(P＞0.05);再灌注后1h,塞来昔布干预组(B3)COX-2 mRNA的表达水平较B2下调,而5-LOX mRNA的表达量较B2组明显升高(P＜0.05);B4组给予MK-886后5-LOX的mRNA表达与B2组比较明显下调(P＜0.05),而COX-2的mRNA表达与B2比较无统计学差异(P＞0.05);两种药物联合作用后COX-2和5-LOX的mRNA表达较B2组均下调(P＜0.05)
2.凋亡:通过流式细胞术分析肝细胞凋亡率显示,与B2组相比,各时点B3,B4,B5组的肝细胞凋亡率显著下降(P＜0.05);B5组凋亡率较B3,B4组明显下降(P＜0.05);而B3组与B4组之间肝细胞凋亡率无显著性差异(P＞0.05)。
3.血清AST、ALT:再灌注后各时点B2组中血清AST、ALT明显高于B1组(P＜0.05);B5组数据明显低于B2组(P＜0.05);B3,B4组血清AST、ALT水平低于B2组,但无统计学差异(P＞0.05)。
4.HE染色:与B1组相比,B2组肝组织改变明显;B3,B4及B5组较B2组肝组织改变减轻;B5组病理学损伤较B3,B4更轻。
结论:COX-2抑制剂塞来昔布及5-LOX抑制剂MK-886减轻肝细胞凋亡,对大鼠肝脏缺血再灌注起保护作用;单独作用肝脏缺血再灌注后,两药之间比较,作用无明显差异;两种药物联合作用COX-2与5-LOX两条通路能更有效的减轻大鼠肝脏缺血再灌注损伤。
Objective:Test the efficacy of the selective COX-2 inhibitor celecoxib、5-LOX inhibitor MK-886 or their combination on hepatic ischemia-reperfusion injury in rat,and to investigate whether the dual inhibition of COX-2 and 5-LOX has a more power protective effect than single inhibition of either COX-2 or 5-LOX alone on hepatic ischemia-reperfusion injury in rat.
Method:Fifty male SD rats were randomly divided into 5 groups:sham-operated control group(B1)、liver ischemia-reperfusion group(B2)、Celecoxib and liver IR group(B3)、MK-886 and liver IR group(B4)、Celecoxib+ MK-886 and liver IR group(B5).Establish a rat model of hepatic ischemia-reperfusion,30 min of total hepatic vascular occlusion and then 30min or 60 min reperfusion were performed to animals in groups B2,B3,B4 and B5.The left hepatic lobes and blood sample which were obtained from the inferior cava vena were taken at 0.5h and 1h after reperfusion.;One step-RT-PCR was used to detect the expressions of COX-2 and 5-LOX;The apoptosis rate of the hepatocytes were detected by flow cytometry.; Hematoxylin Eosin staining was used to classify the injury extent of every samples; Alanine aminotransferase(ALT),aspartate aminotransferase(AST) as well as hepatic histopathological changes were measured;
Result:
1.RT-PCR:The expressions of COX-2 mRNA and 5-LOX mRNA in B2 group was significantly higher compared with the B1 group in different time after reperfusion(P＜0.05);The difference did not reach a statistically significant level in the B3,B4 and B5 groups compared with the B2 group at 30min after reperfusion (P＞0.05);The expressions of COX-2 mRNA was lower in COX-2 inhibitor preconditioning in B3 group than the B2 group at 1h after reperfusion,meanwhile,the expressions of 5-LOX mRNA was significantly higher compared with the B2 group (P＜0.05);The expression of 5-LOX mRNA in the B4 group which was treated with MK-886 was significantly lower than in the B2 group at 1h after reperfusion(P＜0.05), meanwhile,MK-886 had not effect on the expression of the Cox-2(p＞0.05);The expressions of Cox-2 mRNA and 5-lox mRNA in the B5 which were treated with the combination of celecoxib and MK-886 were lower than B2 group at 1h after reperfusion(p＜0.01)
2.Apoptosistic:Analysis of apoptosis by the flow cytometry method showed that the apoptosis rate of the hepatocytes decreased significantly in the B3,B4 and B5 groups compared with the B2 group(P＜0.05);The data of the B5 group was significantly lower than the B3 and B4 groups(P＜0.05);There was no difference in the decline in the apoptosis rate of the hepatocytes between the B3 and B4 groups(P＞0.05).
3.The levels of AST and ALT in blood serum:The datas of B2 group was significantly higher compared with B1 group in different time after reperfusion (P＜0.05);The dates of the B5 group was significantly lower than the B2 group(P＜0.05);The dates of the B3 and B4 groups was lower than the B2 group, which had no significant difference(P＞0.05);The dates of the B5 group was lower than the B3 and B4 groups,but the difference did not reach a statistically significant level(P＞0.05).
4.HE stain:Compared with B1 group,B2 group showed great changes.The pathological lesions were lighter in B3,B4 and B5groups than in B2 group.The pathological lesions were lighter in B5 group than in B3 and B4 group.
Conclusion:COX-2 inhibitor Celecoxib and 5-LOX inhibitor MK-886 were found to be effective in prevention of liver injury by reducing apoptosis in a hepatic I/R model. The efficacy was no different between the celecoxib and MK-886 pretreated groupson hepatic ischemia-reperfusion injury in rat.The dual inhibition of COX-2 and 5-LOX may present a superior protective effect than single inhibition of either COX-2 or 5-LOX alone.
引文
1.Tsung A,Kaizu T,Nakao A,et al.Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptozis.Transplantation 2005;79:196.
2.Kang KJ.Mechanism of hepatic ischemia/reperfusion injury and protection against reperfusion injury.Transpl Proc 2002;34:2659.
3.Schauer RJ,Gerbes AL,Vonier D,et al.Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia.Ann Surg 2004;239:220.
4.Clavien PA,Harvey PR,Strasberg SM.Preservation and reperfusion injuries in liver allografts.An overview and synthesis of current studies.Transplantation 1992;53:957.
5.Lemasters JJ,Thurman RG.The many facets of reperfusion injury.Gastroerlogy,1995,108(4):1317-1320.
6.Jaeschke H.Molecular mechanisms of hepatic ischemia reperfusioninjury and preconditioning.Am J Physiol Gastrointest Liver Physiol,2003,284(1):15-26.
7.Arii S,Teramoto K,Kawamura T.Current progress in the under-standing of and therapeutic strategies for ischemia and reperfusioninjury of the liver.J Hepatobiliary Pancreat Surg,2003,10(3):189-194.
8.金惠铭 尤家禄《病理生理学》人民卫生出版社 2000,ISBN 7-117-03900-0
9.Samuelsson B.L euko trienes mediato rs of immediatehypertensitivity reactions and inflammation.Science,1983;220:568
10.Jaeschke H.Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning.Am J Physiol Gastrointest Liver Physiol,2003,284(1):G15-26.
11.Kupiec-Weglinski JW,Busuttil RW.Ischemia and reperfussion injury in liver transplantation.Transplant Proc,2005,370:1653-1656
12.Kupiec-Weglinski JW,Busuttil RW.Ischemia and reperfusion injury in liver transplantation.[J].Transplant Proc.2005 May;37(4):1653-6.
13.Hiroyuki Katagiri,1 Yoshiya Ito,1 Ken-ichiro Ishii,Role of Thromboxane Derived FromCOX-1 and COX-2 in Hepatic Microcirculatory Dysfunction During Endotoxemia in Mice Hepatology,January 2004
14.Yutaka Sunose MD,Izumi Takeyoshi MD The effect of cyclooxygenase-2inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model,J Am Coll Surg.2001 Jan;192(1):54-62
15.Gendron ME,Thorin E.A change in the redox environment and thromboxane A_2production precede endothelial dysfunction in mice.Am J Physiol Heart Circ Physiol.2007 Oct;293(4):H2508-15.Epub 2007 Jul 20
16.Chen XS,Funk CD.The N-terminal beta-barrel domain of 5-lipoxygenase is essential for nuclear membrane translocation.Biol Chem,2001,276:811-818
17.HammarbergT,RadmarkO.5-lipoxygenasebindscalcium.Biochemistry,2000,38:4441-4447
18.Jagels MA,Hugli TE.N eutrophil chemotactic factorsp romote leukocytosis,a common mechanism for cellular recruitm ent from bone m arrow.J Imm unol,1992;148:1119
19.张丽慧,魏尔清.白三烯受体拮抗剂ONO-1078对大鼠全脑缺血再灌注损伤的保护作用
20.Matsui N,Fukuishi N,Fukuyama Y,et al.Protective effect of the5-lipoxygenase inhibitor ardisiaquinone A on hepatic ischemia-reperfusion injury in rats.Planta Med 2005;71:717.
21.Takamatsu Y,Shimada K,Chij(u|¨)wa K,et al.Role of leukotrieneson hepatic ischemia/reperfusion injury in rats.J Surg Res 2004;119:14.
22.Sener G,Sehirli O,Velioglu-Ogunc A,et al.Montelukast protects against renal ischemia/reperfusion injury in rats.Pharmacol Res 2006;54:65.
23.Titos E,Claria J,Planaguma A,et al.Inhibition of 5-lipoxygenase induces cell growth arrest and apoptosis in rat Kupffer cells:Implications for liver fibrosis.FASEB J 2003;17:1745.
24.Riccioni G,Ilio C.Advances in therapy with antileukotriene drugs.Ann Clin Lab Sci 2004;34:379.
25.Gul Daglar,M.D,Turgut Karace,M.D,Yunus Nadi Yuksek,et al,Effect of Montelukast and MK-886 on Hepatic Ischemia-Reperfusion Injury in Rats. Journal of Surgical Research,2008,131(9):1323-4.
26.Goulet JL,Snouwaert JN,Latour AM,et al.Altered inflammatory responses in leukotriene-deficient mice.Proc Natl Acad Sci USA 1994;91:12852-6.
27.Gavett SH,Madison SL,Chulada PC,et al,Zeldin DC Allergic lung responses are increased in prostaglandin H synthase-deficient mice.J Clin Investig 1999;104:721-32
28.Fiorucci S,Meli R,Bucci M,et al.Dual inhibitors of cyclooxygenase and 5-lipoxygenase.A new avenue in anti-inflammatory therapy.Biochem Pharmacol 2001;62:1433-8
29.Schuligoi R,Amann R,Prenn C,et al.Effects of the cyclooxygenase-2 inhibitor NS-398 on thromboxane and leukotriene synthesis in rat peritoneal cells.Inflamm Res.1998 May;47(5):227-30
30.Kohli V,Madden JF,Bentley RC,et al.Calpain mediates ischemic injury of the liver through modulation of apop tosis and necrosis[J].Gastroenterology,1999,116(1):168-178.
31.Clavien PA,Harvey PR,Strasberg SM.Preservation and reperfusion injuries in liver allografts[J].Transplantation,1992,53(5):肝胆外科杂志2008年2月第16卷第1期Journal of Hepatobiliary Surgery,Vol,16,No.1,Feb.2008 9 957-978.
32.UchidaM,Takemoto Y,NagasueN,et al.Calcium in pig livers following ischemia and reperfusion[J].Journal of Hepatology,1994,20(6):714-719.
33.SakonM,Ariyoshi H,Umeshita K,et al.Ischemia-reperfusion injury of the liver with special reference to calcium-dependent mechanisms[J].Surgery today,2002,32(1):1-12.
34.Kohli V,SelznerM,Madden JF,et al.Endothelial cell and hepatocyte deaths occur by apop tosis after ischemia2reperfusion injury in the rat liver[J].Transplantation,1999,67(8):1099-1105.
35.Trifan OC,Hla T.Cyclooxygenase-2 modulates cellular growth and promotes tumorigenesis.J Cell Mol Med.2003 Jul-Sep;7(3):207-22.
36.Romano M,Claria J.Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy. FASEB J.2003 Nov; 17(14): 1986-95.
37. Claria J, Romano M.Pharmacological intervention of cyclooxygenase-2 and 5-lipoxygenase pathways. Impact on inflammation and cancer. Curr Pharm Des.2005;11(26):3431-47.
38. ladecola C , Alexander M. Cerebral ischemia and inflammation.Curr Opin Neurol, 2001 ,14 (1): 89294.
39. Yutaka Sunose MD, Izumi Takeyoshi MD The effect of cyclooxygenase-2 inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model, J Am Coll Surg. 2001 Jan; 192(1 ):54-62
40. Hayrettin Ozturk Ayten Gezicib and Hulya OzturkThe effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats Hepatol Res. 2006 Feb;34(2):76-83. Epub2005 Dec 27.
41. Hamada T, Tsuchihashi S, Avanesyan A Cyclooxygenase-2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/reperfusion injury. J Immunol. 2008 Feb 1;180(3): 1843-53
42. Ciceri P, RabuffettiM,MonopoliA, et a.l Production of leukotri-enes in a model of focal cerebral ischaemia in the rat[ J].Br J Pharmacol, 2001,133(8): 1323-9.
43. HuangL, Zhao A, WongF, eta.l Leukotriene B4 strongly increa-sesmonocyte chemoattractantprotein-1 in human monocytes [J].ArteriosclerThromb VascBiol, 2004,24(10): 1783-8.
44. TomimotoH, ShibataM, IharaM, eta.l A comparative study on the expression of cyclooxygenase and 5-lipoxygenase during cerebral ischemia in humans[J].ActaNeuropathol, 2002,104(6): 601-7.
45. OhtsukiT,MatsumotoM, HayashiY, et a.l Reperfusioninduces 5-lipoxygenase translocation and leukotriene C4production in ischemic brain[J].Am JPhysiolHeartCircPhysiol, 1995,268: 1249-57.
46. BaskayaM K, HuY,DonaldsonD, eta.l Protective effectof the 5-lipoxygebase inhibitor AA-861 on cerebral edema after transient ishemia[J].JNeurosurg, 1996,85(1): 112-6
47.Kamitani,H.,Geller,M.and Eling,T.Expression of 15-lipoxygenase by human colorectal carcinoma Caco-2 cells during apoptosis and cell differentiation.J.Biol.Chem.,273,21569-21577
48.李昭铸James H-CWang林欣.重复性机械拉伸肌腱成纤维细胞与前列腺素E2和白三烯B4水平异常升高的关系.中华创伤杂志2005;21(4):286-289
49.Cherukuri DP,Nelson MA.Do elevated levels of eicosanoids play a role in head and neck cancer recurrence and metastasis? Implications for prevention and treatment.Cancer Biol Ther.2004 Sep;3(9):853-854.
50.Peters-Golden M,Bailie M,Marshall T,et al.Protection from pulmonary fibrosis in leukotriene-deficient mice.Am J Respir Crit Care Med 2002;165:229-35.
51.Shureiqi I,Lippman SM.Lipoxygenase modulation to reverse carcinogenesis.Cancer Res.2001 Sep 1;61(17):6307-12
52.Kohli V,Selzner M,Maden JF,et al.Endothelial cell and hepatocyte death occur by apoptosis after ischemia2reperfusion injury in the rat liver[J].Transplantation,1999,67(8):109921105.
53.Sasaki H,Matsuno T,Tanaka N,et al.Induction of apoptosis during the early phase of reperfusion after rat liver ischemia[J].Acta Med Okayama,1997,51(6):305.
54.Kuo PC,Drachenberg CI,de la Torre A,et al.Apoptosis and hepatic allograft reperfusion injury[J].Clin Transplant,1998,12(3):219.
55.宋少伟,梁键,刘永峰,等.热缺血再灌注损伤时肝细胞凋亡的变化[J].中华器官移植杂志,2002,23(3):188.
56.Waterhouse NJ,Goldstein JC,Kluck RM,et al.The(Holey)Study of mitochondoria in apoptosis.Methods Cell Biol,2001,66(2):365-391
57.Tsuchihashi S,fondevila C,Shaw GD,etal.Molecular characterization of rat leuckocyte P-selectin glycoprotein ligand-1 and effect of its blockade:protection from ischemia-reperfusion injury in liver transplantation.J Immunol,2006,176(1):616-624.
58.Compagnon P,Lindell S,Ametani MS,et al.Ischemic preconditioning and liver tolerance to warm or cold ischemia:experimental studies in large animals. Transplantation,2005,79(10):1393-1400.
59.Ohkohchi N.Mechanisms of preservation and ischemic/reperfusion injury in liver transplantation.Transplant Proc,2002,34(7):2670-2673
60.Mueller AR,Platz KP,Schumacher G,et al.Mechanisms of preservation and reperfusion injury in human liver transplantation.Transplant Proc,1997,29(8):3455-3457.
61.Gujral JS,Bucci TJ,Farhood A,et al.Mechanism of cell death during warm hepatic ischemia-reperfusion in rats:apoptosis or necrosis.Hepatology,2001,33(2):397-405_
62.马毅,何晓顺,陈规划肝脏缺血再灌注损伤与细胞凋亡.中国病理生理杂志2003,19(7):1005-1008
63.Trocha M,Szelag A.The role of calcium and calcium channel blocking drugs in damage to the liver preserved for transplantation.Ann Transplant,2004,9(3):5-11.
64.Zhang SJ,Chen S.The role of ischemic preconditioning in rat liver graft.Transplant Proc,2004,36(7):1970-1972
65.Suzuki S,Kono H,Nakamura S.Role of cytokines in hepatic ischemia and reperfusion injury.Nippon Geka Gakkai Zasshi,1999,100(5):325-330
66.赵浩亮,武小勇,李正中,等.丹参对肝脏保存再灌注时Bcl-2,Bax表达和肝细胞凋亡的影响.中华普通外科杂志,2001,16(10):600-601
67.Zhang Y,Ye QF,Lu L,et al.Panax notoginseg saponins preconditioning protects rat liver grafts from ischemia/reperfusion injury via an antiapoptotic pathway.Hepatobiliary Pancreat Dis Int,2005,4(2):207-212
1.Choi DW.Ischemia-induced neuronal apoptosis[J].Curr Opin Neurobi-ol,1996,6(5):667-672.
2.Kerr JF,Wyllie AH,Currie AR.Apoptosis:A basic biological phenome2 non with wide2ranging implications in tissue kinetics[J].Br J Cancer,1972,26(4):239-257.
3.DingWX,Yin XM.Dissection of themultip lemechanisms of TNF-alphainduced apop tosis in liver injury[J].J Cell Mol Med,2004,8:445-454.
4.NeumanMG.Apop tosis in diseases of the liver[J].Crit Rev Clin Lab Sci,2001,38:109-166.
5.KohiiV,SelznerM,MaddenJF,et al.Endothelial cell and hepatocytedeaths occur by apoptosis after isehemia-reperfusion injury in the ra tliver.Transplantation,1999,67(8):1099-1105.
6.SasakiH,MatsunoT,Tanaka N,et al.Induction of apoptosis during the early phase of reperfusion after rat live risehemia.Aeta Med Okayama,1997,51(6):305-312.
7.KuoPC,DrachenbergCI,de la Torre A,et al.Apoptosis and hepatic allograft reperfusion injury;Clin Transplant,1998,12(3):219-223.
8.宋少伟,梁键,刘永峰,等.热缺血再灌注损伤时肝细胞凋亡的变化.中华器官移植杂志,2002,23(3):188.
9.Leist M,Gantner F,Bohlinger I,et al..Murine hepatocyte apoptosis induced in vitro and vivo by TNF-alpha requires transcriptional arrest[J].J Immunol,1994,153(4):1778-1782.
10.Tsukidate L,Yamamoto K,Snyder J,et al.Microtubule antagonists activate programmed cell death(apoptosis) in culture rat hepatocytes[J].AmJ Pathol,1993,143(3):918-921.
11.Davis A,Chen A.Transforming growth factor beta liver regeneration:the stage may be set,but what's the script[J].Hepatology,1996,23(6):1703-1706
12.孙凯,刘志苏,孙权.大鼠肝脏缺血再灌注时肝细胞凋亡与Bcl-2蛋白表达的关系[J].肝脏,2003,8(3):12-15.
13.Oltval Z,Milliman C,Korsmeyer S.Bcl-2 heterodimerizes in vivo with a conserved homolog,bax,that accelerates programmed cell death[J].Cell,1993,74(4):609-619.
14.Nagata S.Apoptosis by death factor[J].Cell,1997,88(3):355-365.
15.Migashita T,Krajewski S,Krajewska M,et al.Tumor suppressor p53 is a regulator of Bcl-2 and bax gene expression in vitro and in vivo[J],Oncogene,1994,9(10):1799.
16.Cursio R,Gugenheim J,Ricci JE,et al.Caspase inhibition protects from liver injury following ischemia and repro fusion in rats[J].Transplint,2000,13[Suppl 1]:568-572.
17.Selzner M,R(u|¨)diger HA,Sindram D,et al.Mechanisms of ischemic injury are different in the steatotic and normal rat liver[J].Hepatology,2000,32(6):1280-1288
18..Singh AK,Mani H,Seth P.Picroliv preconditioning protects the rat liver against ischemia-reperfusion injury[J].Eur J Pharmacol,2000,395(3):2292239.
19.Goto S,Matsumoto L,Kamade N,et al.The induction of immediate early gene in postischemia and transplanted livers in rats[J].Transplantation,1994,58(1):840-845.
20.Schlossberg H,Zhang Y,Dadus L,et al.Expression of c-los and c-jun during hepatocellular remodeling following ischemia/reperfusion in mouse[J].Hepatology,1996,23(3):1546-1555.
21.Tejima K,AraiM,Ikeda H,et al.Ischemic p reconditioning protects hepatocytes viare active oxygen species derived from Kupffercells in rats[J].Gastroenterology,2004,127:1488-1496.
22.Sun K,Liu ZS,Sun Q.Role of mitochondria in cell apop tosis during hepatic ischemia-reperfusion injury and protective effect ofischemic postconditioning [J].World JGastroenterol,2004,10:1934-1938.
23. Cursio R, Gugenheim J, Ricci JE, et al.Caspase inhibition p rotects from liver injury following ischemia and reperfusion in rats[ J ]. Transp 1 Int, 2000,13: S568-572.
24. Tsung A, Kaizu T, Nakao A, et al. Ethylpyruvate ameliorates liver ischemia - reperfusion injury by decreasing hepatic necrosis andapop tosis [ J ]. Transp lantation, 2005, 79:196-204.
25. Horie Y, Yamagishi Y, Kato S, et al. Low- dose ethanol attenuates gut ischemia / reperfusion - induced liver injury in rats via nitricoxide p roduction [ J ]. J Gastroenterol Hepatol, 2003,18: 211 - 217.
26. Yamashita H,Akamine S, Sumida Y, et al. Inhaled nitric oxide attenuates apop tosis in ischemia - reperfusion injury of the rabbit lung[ J ]. Ann Thorac Surg, 2004, 78: 292 - 297.
27. Maejima Y, Adachi S, Ito H, et al. Nitricoxide inhibits ischemia - reperfusion - in-duced myocardial apop tosis by modulating cyclin A - associated kinase activity [ J ]. Cardiovasc Res, 2003, 59: 308 - 320.
28. Ryter SW, Otterbein LE. Carbon monoxidein biology and medicine [ J ]. Bioessays,2004,26: 270 - 280.
29. Zuckerbraun BS, McCloskey CA, Gallo D, et al. Carbon monoxide prevent smultip leorgan injury in a model of hemorrhagic shockand resuscitation [ J ]. Shock, 2005,23:527-532.
30. Kaizu T, Nakao A, TsungA, et al. Carbonmonoxide inhalation ameliorates cold ischemia / reperfusion injury after rat liver transp lantation [ J ]. Surgery, 2005, 138:229-235.
31. OttMC, Scott JR, Bihari A, et al. Inhalation of carbon monoxide p revents liver injury and inflammation following hind limb ischemia / reperfusion [ J ]. FASEB J, 2005, 19:106-108.
32. Sass G, Soares MC, Yamashita K, et al.Heme oxygenase - 1 and its reaction product, carbon monoxide, p revent inflammation - related apop totic liver damage in mice [ J ].Hepatology, 2003, 38: 909 - 918.
33. Wunder C, Brock RW, Frantz S, et al.Carbon monoxide, but not endothelin - 1,plays a major role for the hepatic microcirculation in a murine model of early systemic inflammation[J].Crit Care Med,2005,33:2323-2331.
34.Contreras JL,Vilatoba M,Eckstein C,et al.Caspase-8 and caspase-3 small interferingRNA decreases ischemia/reperfusion injury tothe liver in mice[J].Surgery,2004,136:390-400.
35.Sakai T,Takaya S,Fukuda A,et al.Evaluation of warm ischemia-reperfusion injury using heat shock protein in the rat liver[J].Transp l Int,2003,16:88-99.
36.Kienle K,RentschM,M(u|¨)ller T,et al.Ex ression ofBCL-2in liver grafts after adeno viral transfer imp roves survival following p rolonged ischemia and reperfusion in rat liverransp lantation[J].Transp lant Proc,2005,37:439-441.
37.Jawan B,Goto S,Pan TL,et al.The protective mechanism of magnolol,a Chinese herb drug,against warm ischemia-reperfusion injury of rat liver[J].J Surg Res,2003,110:378-382.
38.Oshiro T,ShiraishiM,Muto Y.Adenovirusmediated gene transfer of antiapop totic p roteinin hepatic ischemia-reperfusion injury:theparadoxical effect of Bcl -2 exp-ression in thereperfused liver[J].J Surg Res,2002,103:30-36.
2.Kang KJ.Mechanism of hepatic ischemia/reperfusion injury and protection against reperfusion injury.Transpl Proc 2002;34:2659.
3.Schauer RJ,Gerbes AL,Vonier D,et al.Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia.Ann Surg 2004;239:220.
4.Clavien PA,Harvey PR,Strasberg SM.Preservation and reperfusion injuries in liver allografts.An overview and synthesis of current studies.Transplantation 1992;53:957.
5.Lemasters JJ,Thurman RG.The many facets of reperfusion injury.Gastroerlogy,1995,108(4):1317-1320.
6.Jaeschke H.Molecular mechanisms of hepatic ischemia reperfusioninjury and preconditioning.Am J Physiol Gastrointest Liver Physiol,2003,284(1):15-26.
7.Arii S,Teramoto K,Kawamura T.Current progress in the under-standing of and therapeutic strategies for ischemia and reperfusioninjury of the liver.J Hepatobiliary Pancreat Surg,2003,10(3):189-194.
8.金惠铭 尤家禄《病理生理学》人民卫生出版社 2000,ISBN 7-117-03900-0
9.Samuelsson B.L euko trienes mediato rs of immediatehypertensitivity reactions and inflammation.Science,1983;220:568
10.Jaeschke H.Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning.Am J Physiol Gastrointest Liver Physiol,2003,284(1):G15-26.
11.Kupiec-Weglinski JW,Busuttil RW.Ischemia and reperfussion injury in liver transplantation.Transplant Proc,2005,370:1653-1656
12.Kupiec-Weglinski JW,Busuttil RW.Ischemia and reperfusion injury in liver transplantation.[J].Transplant Proc.2005 May;37(4):1653-6.
13.Hiroyuki Katagiri,1 Yoshiya Ito,1 Ken-ichiro Ishii,Role of Thromboxane Derived FromCOX-1 and COX-2 in Hepatic Microcirculatory Dysfunction During Endotoxemia in Mice Hepatology,January 2004
14.Yutaka Sunose MD,Izumi Takeyoshi MD The effect of cyclooxygenase-2inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model,J Am Coll Surg.2001 Jan;192(1):54-62
15.Gendron ME,Thorin E.A change in the redox environment and thromboxane A_2production precede endothelial dysfunction in mice.Am J Physiol Heart Circ Physiol.2007 Oct;293(4):H2508-15.Epub 2007 Jul 20
16.Chen XS,Funk CD.The N-terminal beta-barrel domain of 5-lipoxygenase is essential for nuclear membrane translocation.Biol Chem,2001,276:811-818
17.HammarbergT,RadmarkO.5-lipoxygenasebindscalcium.Biochemistry,2000,38:4441-4447
18.Jagels MA,Hugli TE.N eutrophil chemotactic factorsp romote leukocytosis,a common mechanism for cellular recruitm ent from bone m arrow.J Imm unol,1992;148:1119
19.张丽慧,魏尔清.白三烯受体拮抗剂ONO-1078对大鼠全脑缺血再灌注损伤的保护作用
20.Matsui N,Fukuishi N,Fukuyama Y,et al.Protective effect of the5-lipoxygenase inhibitor ardisiaquinone A on hepatic ischemia-reperfusion injury in rats.Planta Med 2005;71:717.
21.Takamatsu Y,Shimada K,Chij(u|¨)wa K,et al.Role of leukotrieneson hepatic ischemia/reperfusion injury in rats.J Surg Res 2004;119:14.
22.Sener G,Sehirli O,Velioglu-Ogunc A,et al.Montelukast protects against renal ischemia/reperfusion injury in rats.Pharmacol Res 2006;54:65.
23.Titos E,Claria J,Planaguma A,et al.Inhibition of 5-lipoxygenase induces cell growth arrest and apoptosis in rat Kupffer cells:Implications for liver fibrosis.FASEB J 2003;17:1745.
24.Riccioni G,Ilio C.Advances in therapy with antileukotriene drugs.Ann Clin Lab Sci 2004;34:379.
25.Gul Daglar,M.D,Turgut Karace,M.D,Yunus Nadi Yuksek,et al,Effect of Montelukast and MK-886 on Hepatic Ischemia-Reperfusion Injury in Rats. Journal of Surgical Research,2008,131(9):1323-4.
26.Goulet JL,Snouwaert JN,Latour AM,et al.Altered inflammatory responses in leukotriene-deficient mice.Proc Natl Acad Sci USA 1994;91:12852-6.
27.Gavett SH,Madison SL,Chulada PC,et al,Zeldin DC Allergic lung responses are increased in prostaglandin H synthase-deficient mice.J Clin Investig 1999;104:721-32
28.Fiorucci S,Meli R,Bucci M,et al.Dual inhibitors of cyclooxygenase and 5-lipoxygenase.A new avenue in anti-inflammatory therapy.Biochem Pharmacol 2001;62:1433-8
29.Schuligoi R,Amann R,Prenn C,et al.Effects of the cyclooxygenase-2 inhibitor NS-398 on thromboxane and leukotriene synthesis in rat peritoneal cells.Inflamm Res.1998 May;47(5):227-30
30.Kohli V,Madden JF,Bentley RC,et al.Calpain mediates ischemic injury of the liver through modulation of apop tosis and necrosis[J].Gastroenterology,1999,116(1):168-178.
31.Clavien PA,Harvey PR,Strasberg SM.Preservation and reperfusion injuries in liver allografts[J].Transplantation,1992,53(5):肝胆外科杂志2008年2月第16卷第1期Journal of Hepatobiliary Surgery,Vol,16,No.1,Feb.2008 9 957-978.
32.UchidaM,Takemoto Y,NagasueN,et al.Calcium in pig livers following ischemia and reperfusion[J].Journal of Hepatology,1994,20(6):714-719.
33.SakonM,Ariyoshi H,Umeshita K,et al.Ischemia-reperfusion injury of the liver with special reference to calcium-dependent mechanisms[J].Surgery today,2002,32(1):1-12.
34.Kohli V,SelznerM,Madden JF,et al.Endothelial cell and hepatocyte deaths occur by apop tosis after ischemia2reperfusion injury in the rat liver[J].Transplantation,1999,67(8):1099-1105.
35.Trifan OC,Hla T.Cyclooxygenase-2 modulates cellular growth and promotes tumorigenesis.J Cell Mol Med.2003 Jul-Sep;7(3):207-22.
36.Romano M,Claria J.Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy. FASEB J.2003 Nov; 17(14): 1986-95.
37. Claria J, Romano M.Pharmacological intervention of cyclooxygenase-2 and 5-lipoxygenase pathways. Impact on inflammation and cancer. Curr Pharm Des.2005;11(26):3431-47.
38. ladecola C , Alexander M. Cerebral ischemia and inflammation.Curr Opin Neurol, 2001 ,14 (1): 89294.
39. Yutaka Sunose MD, Izumi Takeyoshi MD The effect of cyclooxygenase-2 inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model, J Am Coll Surg. 2001 Jan; 192(1 ):54-62
40. Hayrettin Ozturk Ayten Gezicib and Hulya OzturkThe effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats Hepatol Res. 2006 Feb;34(2):76-83. Epub2005 Dec 27.
41. Hamada T, Tsuchihashi S, Avanesyan A Cyclooxygenase-2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/reperfusion injury. J Immunol. 2008 Feb 1;180(3): 1843-53
42. Ciceri P, RabuffettiM,MonopoliA, et a.l Production of leukotri-enes in a model of focal cerebral ischaemia in the rat[ J].Br J Pharmacol, 2001,133(8): 1323-9.
43. HuangL, Zhao A, WongF, eta.l Leukotriene B4 strongly increa-sesmonocyte chemoattractantprotein-1 in human monocytes [J].ArteriosclerThromb VascBiol, 2004,24(10): 1783-8.
44. TomimotoH, ShibataM, IharaM, eta.l A comparative study on the expression of cyclooxygenase and 5-lipoxygenase during cerebral ischemia in humans[J].ActaNeuropathol, 2002,104(6): 601-7.
45. OhtsukiT,MatsumotoM, HayashiY, et a.l Reperfusioninduces 5-lipoxygenase translocation and leukotriene C4production in ischemic brain[J].Am JPhysiolHeartCircPhysiol, 1995,268: 1249-57.
46. BaskayaM K, HuY,DonaldsonD, eta.l Protective effectof the 5-lipoxygebase inhibitor AA-861 on cerebral edema after transient ishemia[J].JNeurosurg, 1996,85(1): 112-6
47.Kamitani,H.,Geller,M.and Eling,T.Expression of 15-lipoxygenase by human colorectal carcinoma Caco-2 cells during apoptosis and cell differentiation.J.Biol.Chem.,273,21569-21577
48.李昭铸James H-CWang林欣.重复性机械拉伸肌腱成纤维细胞与前列腺素E2和白三烯B4水平异常升高的关系.中华创伤杂志2005;21(4):286-289
49.Cherukuri DP,Nelson MA.Do elevated levels of eicosanoids play a role in head and neck cancer recurrence and metastasis? Implications for prevention and treatment.Cancer Biol Ther.2004 Sep;3(9):853-854.
50.Peters-Golden M,Bailie M,Marshall T,et al.Protection from pulmonary fibrosis in leukotriene-deficient mice.Am J Respir Crit Care Med 2002;165:229-35.
51.Shureiqi I,Lippman SM.Lipoxygenase modulation to reverse carcinogenesis.Cancer Res.2001 Sep 1;61(17):6307-12
52.Kohli V,Selzner M,Maden JF,et al.Endothelial cell and hepatocyte death occur by apoptosis after ischemia2reperfusion injury in the rat liver[J].Transplantation,1999,67(8):109921105.
53.Sasaki H,Matsuno T,Tanaka N,et al.Induction of apoptosis during the early phase of reperfusion after rat liver ischemia[J].Acta Med Okayama,1997,51(6):305.
54.Kuo PC,Drachenberg CI,de la Torre A,et al.Apoptosis and hepatic allograft reperfusion injury[J].Clin Transplant,1998,12(3):219.
55.宋少伟,梁键,刘永峰,等.热缺血再灌注损伤时肝细胞凋亡的变化[J].中华器官移植杂志,2002,23(3):188.
56.Waterhouse NJ,Goldstein JC,Kluck RM,et al.The(Holey)Study of mitochondoria in apoptosis.Methods Cell Biol,2001,66(2):365-391
57.Tsuchihashi S,fondevila C,Shaw GD,etal.Molecular characterization of rat leuckocyte P-selectin glycoprotein ligand-1 and effect of its blockade:protection from ischemia-reperfusion injury in liver transplantation.J Immunol,2006,176(1):616-624.
58.Compagnon P,Lindell S,Ametani MS,et al.Ischemic preconditioning and liver tolerance to warm or cold ischemia:experimental studies in large animals. Transplantation,2005,79(10):1393-1400.
59.Ohkohchi N.Mechanisms of preservation and ischemic/reperfusion injury in liver transplantation.Transplant Proc,2002,34(7):2670-2673
60.Mueller AR,Platz KP,Schumacher G,et al.Mechanisms of preservation and reperfusion injury in human liver transplantation.Transplant Proc,1997,29(8):3455-3457.
61.Gujral JS,Bucci TJ,Farhood A,et al.Mechanism of cell death during warm hepatic ischemia-reperfusion in rats:apoptosis or necrosis.Hepatology,2001,33(2):397-405_
62.马毅,何晓顺,陈规划肝脏缺血再灌注损伤与细胞凋亡.中国病理生理杂志2003,19(7):1005-1008
63.Trocha M,Szelag A.The role of calcium and calcium channel blocking drugs in damage to the liver preserved for transplantation.Ann Transplant,2004,9(3):5-11.
64.Zhang SJ,Chen S.The role of ischemic preconditioning in rat liver graft.Transplant Proc,2004,36(7):1970-1972
65.Suzuki S,Kono H,Nakamura S.Role of cytokines in hepatic ischemia and reperfusion injury.Nippon Geka Gakkai Zasshi,1999,100(5):325-330
66.赵浩亮,武小勇,李正中,等.丹参对肝脏保存再灌注时Bcl-2,Bax表达和肝细胞凋亡的影响.中华普通外科杂志,2001,16(10):600-601
67.Zhang Y,Ye QF,Lu L,et al.Panax notoginseg saponins preconditioning protects rat liver grafts from ischemia/reperfusion injury via an antiapoptotic pathway.Hepatobiliary Pancreat Dis Int,2005,4(2):207-212
1.Choi DW.Ischemia-induced neuronal apoptosis[J].Curr Opin Neurobi-ol,1996,6(5):667-672.
2.Kerr JF,Wyllie AH,Currie AR.Apoptosis:A basic biological phenome2 non with wide2ranging implications in tissue kinetics[J].Br J Cancer,1972,26(4):239-257.
3.DingWX,Yin XM.Dissection of themultip lemechanisms of TNF-alphainduced apop tosis in liver injury[J].J Cell Mol Med,2004,8:445-454.
4.NeumanMG.Apop tosis in diseases of the liver[J].Crit Rev Clin Lab Sci,2001,38:109-166.
5.KohiiV,SelznerM,MaddenJF,et al.Endothelial cell and hepatocytedeaths occur by apoptosis after isehemia-reperfusion injury in the ra tliver.Transplantation,1999,67(8):1099-1105.
6.SasakiH,MatsunoT,Tanaka N,et al.Induction of apoptosis during the early phase of reperfusion after rat live risehemia.Aeta Med Okayama,1997,51(6):305-312.
7.KuoPC,DrachenbergCI,de la Torre A,et al.Apoptosis and hepatic allograft reperfusion injury;Clin Transplant,1998,12(3):219-223.
8.宋少伟,梁键,刘永峰,等.热缺血再灌注损伤时肝细胞凋亡的变化.中华器官移植杂志,2002,23(3):188.
9.Leist M,Gantner F,Bohlinger I,et al..Murine hepatocyte apoptosis induced in vitro and vivo by TNF-alpha requires transcriptional arrest[J].J Immunol,1994,153(4):1778-1782.
10.Tsukidate L,Yamamoto K,Snyder J,et al.Microtubule antagonists activate programmed cell death(apoptosis) in culture rat hepatocytes[J].AmJ Pathol,1993,143(3):918-921.
11.Davis A,Chen A.Transforming growth factor beta liver regeneration:the stage may be set,but what's the script[J].Hepatology,1996,23(6):1703-1706
12.孙凯,刘志苏,孙权.大鼠肝脏缺血再灌注时肝细胞凋亡与Bcl-2蛋白表达的关系[J].肝脏,2003,8(3):12-15.
13.Oltval Z,Milliman C,Korsmeyer S.Bcl-2 heterodimerizes in vivo with a conserved homolog,bax,that accelerates programmed cell death[J].Cell,1993,74(4):609-619.
14.Nagata S.Apoptosis by death factor[J].Cell,1997,88(3):355-365.
15.Migashita T,Krajewski S,Krajewska M,et al.Tumor suppressor p53 is a regulator of Bcl-2 and bax gene expression in vitro and in vivo[J],Oncogene,1994,9(10):1799.
16.Cursio R,Gugenheim J,Ricci JE,et al.Caspase inhibition protects from liver injury following ischemia and repro fusion in rats[J].Transplint,2000,13[Suppl 1]:568-572.
17.Selzner M,R(u|¨)diger HA,Sindram D,et al.Mechanisms of ischemic injury are different in the steatotic and normal rat liver[J].Hepatology,2000,32(6):1280-1288
18..Singh AK,Mani H,Seth P.Picroliv preconditioning protects the rat liver against ischemia-reperfusion injury[J].Eur J Pharmacol,2000,395(3):2292239.
19.Goto S,Matsumoto L,Kamade N,et al.The induction of immediate early gene in postischemia and transplanted livers in rats[J].Transplantation,1994,58(1):840-845.
20.Schlossberg H,Zhang Y,Dadus L,et al.Expression of c-los and c-jun during hepatocellular remodeling following ischemia/reperfusion in mouse[J].Hepatology,1996,23(3):1546-1555.
21.Tejima K,AraiM,Ikeda H,et al.Ischemic p reconditioning protects hepatocytes viare active oxygen species derived from Kupffercells in rats[J].Gastroenterology,2004,127:1488-1496.
22.Sun K,Liu ZS,Sun Q.Role of mitochondria in cell apop tosis during hepatic ischemia-reperfusion injury and protective effect ofischemic postconditioning [J].World JGastroenterol,2004,10:1934-1938.
23. Cursio R, Gugenheim J, Ricci JE, et al.Caspase inhibition p rotects from liver injury following ischemia and reperfusion in rats[ J ]. Transp 1 Int, 2000,13: S568-572.
24. Tsung A, Kaizu T, Nakao A, et al. Ethylpyruvate ameliorates liver ischemia - reperfusion injury by decreasing hepatic necrosis andapop tosis [ J ]. Transp lantation, 2005, 79:196-204.
25. Horie Y, Yamagishi Y, Kato S, et al. Low- dose ethanol attenuates gut ischemia / reperfusion - induced liver injury in rats via nitricoxide p roduction [ J ]. J Gastroenterol Hepatol, 2003,18: 211 - 217.
26. Yamashita H,Akamine S, Sumida Y, et al. Inhaled nitric oxide attenuates apop tosis in ischemia - reperfusion injury of the rabbit lung[ J ]. Ann Thorac Surg, 2004, 78: 292 - 297.
27. Maejima Y, Adachi S, Ito H, et al. Nitricoxide inhibits ischemia - reperfusion - in-duced myocardial apop tosis by modulating cyclin A - associated kinase activity [ J ]. Cardiovasc Res, 2003, 59: 308 - 320.
28. Ryter SW, Otterbein LE. Carbon monoxidein biology and medicine [ J ]. Bioessays,2004,26: 270 - 280.
29. Zuckerbraun BS, McCloskey CA, Gallo D, et al. Carbon monoxide prevent smultip leorgan injury in a model of hemorrhagic shockand resuscitation [ J ]. Shock, 2005,23:527-532.
30. Kaizu T, Nakao A, TsungA, et al. Carbonmonoxide inhalation ameliorates cold ischemia / reperfusion injury after rat liver transp lantation [ J ]. Surgery, 2005, 138:229-235.
31. OttMC, Scott JR, Bihari A, et al. Inhalation of carbon monoxide p revents liver injury and inflammation following hind limb ischemia / reperfusion [ J ]. FASEB J, 2005, 19:106-108.
32. Sass G, Soares MC, Yamashita K, et al.Heme oxygenase - 1 and its reaction product, carbon monoxide, p revent inflammation - related apop totic liver damage in mice [ J ].Hepatology, 2003, 38: 909 - 918.
33. Wunder C, Brock RW, Frantz S, et al.Carbon monoxide, but not endothelin - 1,plays a major role for the hepatic microcirculation in a murine model of early systemic inflammation[J].Crit Care Med,2005,33:2323-2331.
34.Contreras JL,Vilatoba M,Eckstein C,et al.Caspase-8 and caspase-3 small interferingRNA decreases ischemia/reperfusion injury tothe liver in mice[J].Surgery,2004,136:390-400.
35.Sakai T,Takaya S,Fukuda A,et al.Evaluation of warm ischemia-reperfusion injury using heat shock protein in the rat liver[J].Transp l Int,2003,16:88-99.
36.Kienle K,RentschM,M(u|¨)ller T,et al.Ex ression ofBCL-2in liver grafts after adeno viral transfer imp roves survival following p rolonged ischemia and reperfusion in rat liverransp lantation[J].Transp lant Proc,2005,37:439-441.
37.Jawan B,Goto S,Pan TL,et al.The protective mechanism of magnolol,a Chinese herb drug,against warm ischemia-reperfusion injury of rat liver[J].J Surg Res,2003,110:378-382.
38.Oshiro T,ShiraishiM,Muto Y.Adenovirusmediated gene transfer of antiapop totic p roteinin hepatic ischemia-reperfusion injury:theparadoxical effect of Bcl -2 exp-ression in thereperfused liver[J].J Surg Res,2002,103:30-36.