依达拉奉对大鼠小肠缺血再灌注损伤保护作用的实验研究
摘要
目的通过大鼠小肠缺血再灌注(Ischemia-reperfusion I/R)对小肠粘膜的损伤程度,促炎因子和抗炎因子的释放方面研究依达拉奉(Edaravone 3-甲基-i-苯基-2-N比啉唑-5-酮)对小肠I/R损伤的保护作用,从而为临床防治小肠I/R损伤提供一个新的治疗思路。
方法SPF级健康成年SD大鼠60只,体重在280g-320g之间,均为雄性,随机分为对照组、I/R组和依达拉奉组3组(n=20),每组根据再灌注时间不同再分为2小时组和4小时组两个亚组(n=10)。于实验前一天禁食,自由饮水,实验前2小时行含绿色荧光蛋白大肠杆菌灌胃。实验中对照组开腹后仅分离肠系膜上动脉(SMA)后关腹;I/R组分离SMA后以无创动脉夹夹闭,45min后松开动脉夹,分别于再灌注2小时、4小时时采集标本;依达拉奉组夹闭SMA45min后行再灌注,于再灌注前5min经大鼠尾静脉按3 mg/kg剂量注入依达拉奉,分别于再灌注2小时、4小时时采集标本。小肠粘膜组织HE染色后病理学检测,对门静脉血、肝脏组织及脾脏组织行细菌学培养,ELISA法检测大鼠血清IL-1β、IL-6、IL-10和TNF-α的含量。
结果(1)肠粘膜病理变化:对照组大鼠小肠绒毛完整,排列整齐,炎性细胞浸润少,无明显出血及脱落。I/R组大鼠在再灌注2小时和4小时小肠绒毛上皮顶端与固有层分离,固有层出血和溃疡,大量炎性细胞浸润,粘膜绒毛坏死脱落。与I/R组相比,依达拉奉组在再灌注2小时和4小时肠粘膜绒毛损伤减轻,坏死,脱落减少。依达拉奉组病理损伤评分低于I/R组(p＜0.05)。(2)细胞因子变化:I/R组和依达拉奉组再灌注2小时和4小时大鼠血清中炎性细胞因子IL-1β、IL-6、TNF-α含量明显高于对照组(P＜0.05),I/R组高于依达拉奉组(p＜0.05),I/R组和依达拉奉组再灌注2小时和4小时时大鼠血清中抗炎因子IL-10含量明显高于对照组(p＜0.05),依达拉奉组高于I/R组(p＜0.05)。(3)细菌移位情况:I/R组、依达拉奉组再灌注2小时、4小时后大鼠门静脉、肝脏、脾脏的细菌移位明显高于正常对照组(p＜0.05),I/R组高于依达拉奉组(p＜0.05)。
结论依达拉奉对大鼠小肠I/R具有保护作用。(1)依达拉奉能有效减轻大鼠小肠I/R损伤小肠粘膜绒毛的坏死程度,减少绒毛脱落,保护大鼠小肠粘膜结构的完整性和正常生理功能。(2)依达拉奉能明显减少大鼠小肠I/R损伤促炎细胞因子IL-1β、IL-6、TNF-α的含量和促进抗炎细胞因子IL-10的释放。(3)依达拉奉可明显降低大鼠小肠I/R损伤后肠道细菌移位。
[Objective]To study the protective effects of edaravone against ischemia-reperfusion injury of small intestine in rat intestinal mucosa damage,inflammatory factorand anti-inflammatory factor release in order to find a way to protect clinical small intestine from I/R injury.
[Methods]Sixty SD rats weighted about 280g-320g were divided into three groups randomly:control group,I/R group,edaravone group(n=20).Each group was divided into two subgroups according to time of reperfusion (n=10),The control group:the rats underwent a 3cm medium length-wise laparotomy,exposure of the small intestine,identification and dissection of the SMA and then,closure abdominal cavity.The I/R group:the rats were operated by occlusion of SMA for 45 min,and then,same with control group. The edaravone group:the rats were operated by occlusion of SMA for 45 min, 5 min before reperfusion,inject edaravone through tail vein(3mg/kg),and then,same with I/R group.At the end of the operation,the rats were sacrificed,and dissected 10cm segment of ileum to determination of intestines mucous membrane's injury.The serum of TNF-α,IL-1β, IL-6,IL-10 are measured by ELISA.Cut tissues from liver and spleen at the same weight and portal vein blood to detect bacteria.
[Results](1)The changes of intestinal mucosa:In I/R group,the intestinal mucosa presented dilated and exposed capillaries and denuded villi,some of villi hemorrhage,ulceration.The lamina propria was edema and infiltrated with inflammatory cells.The intestinal mucosal structure maintain intact with lifting of the epithelial layer from the lamina propria and moderate extension of the subepithelial space in edaravone group.In edaravone group,histopathologic scores were significantly lower than that of I/R group.(2) Compared with Contraol group,the serum contents of TNF-α,IL-1β,IL-6 in I/R group,edaravone group are obviously higher, and the edaravone group is lower than that of I/R group.The contents of IL-10 in other two groups are lower than that of control group,and edaravone group are higher than that of I/R group.(3)Compared with control group, the bacteria transposition in I/R group,edaravone group is obviously higher,and the edaravone group is lower than that of I/R group.
[Conclusion]Edaravone can protects against small intestinal ischemia-reperfusion injury in rats.(1)Edaravone makes small intestinal mucosal damage degree alleviated in rat I/R injury.(2) Edaravone can reduce the contents of inflammatory TNF-α,IL-1β,IL-6 and promote the contents of anti-inflammatory medium Ih-10 in rat I/R injury.(3) Edaravone can reduce the bacterias transposition of small intestine in rat I/R ingury.
方法SPF级健康成年SD大鼠60只,体重在280g-320g之间,均为雄性,随机分为对照组、I/R组和依达拉奉组3组(n=20),每组根据再灌注时间不同再分为2小时组和4小时组两个亚组(n=10)。于实验前一天禁食,自由饮水,实验前2小时行含绿色荧光蛋白大肠杆菌灌胃。实验中对照组开腹后仅分离肠系膜上动脉(SMA)后关腹;I/R组分离SMA后以无创动脉夹夹闭,45min后松开动脉夹,分别于再灌注2小时、4小时时采集标本;依达拉奉组夹闭SMA45min后行再灌注,于再灌注前5min经大鼠尾静脉按3 mg/kg剂量注入依达拉奉,分别于再灌注2小时、4小时时采集标本。小肠粘膜组织HE染色后病理学检测,对门静脉血、肝脏组织及脾脏组织行细菌学培养,ELISA法检测大鼠血清IL-1β、IL-6、IL-10和TNF-α的含量。
结果(1)肠粘膜病理变化:对照组大鼠小肠绒毛完整,排列整齐,炎性细胞浸润少,无明显出血及脱落。I/R组大鼠在再灌注2小时和4小时小肠绒毛上皮顶端与固有层分离,固有层出血和溃疡,大量炎性细胞浸润,粘膜绒毛坏死脱落。与I/R组相比,依达拉奉组在再灌注2小时和4小时肠粘膜绒毛损伤减轻,坏死,脱落减少。依达拉奉组病理损伤评分低于I/R组(p＜0.05)。(2)细胞因子变化:I/R组和依达拉奉组再灌注2小时和4小时大鼠血清中炎性细胞因子IL-1β、IL-6、TNF-α含量明显高于对照组(P＜0.05),I/R组高于依达拉奉组(p＜0.05),I/R组和依达拉奉组再灌注2小时和4小时时大鼠血清中抗炎因子IL-10含量明显高于对照组(p＜0.05),依达拉奉组高于I/R组(p＜0.05)。(3)细菌移位情况:I/R组、依达拉奉组再灌注2小时、4小时后大鼠门静脉、肝脏、脾脏的细菌移位明显高于正常对照组(p＜0.05),I/R组高于依达拉奉组(p＜0.05)。
结论依达拉奉对大鼠小肠I/R具有保护作用。(1)依达拉奉能有效减轻大鼠小肠I/R损伤小肠粘膜绒毛的坏死程度,减少绒毛脱落,保护大鼠小肠粘膜结构的完整性和正常生理功能。(2)依达拉奉能明显减少大鼠小肠I/R损伤促炎细胞因子IL-1β、IL-6、TNF-α的含量和促进抗炎细胞因子IL-10的释放。(3)依达拉奉可明显降低大鼠小肠I/R损伤后肠道细菌移位。
[Objective]To study the protective effects of edaravone against ischemia-reperfusion injury of small intestine in rat intestinal mucosa damage,inflammatory factorand anti-inflammatory factor release in order to find a way to protect clinical small intestine from I/R injury.
[Methods]Sixty SD rats weighted about 280g-320g were divided into three groups randomly:control group,I/R group,edaravone group(n=20).Each group was divided into two subgroups according to time of reperfusion (n=10),The control group:the rats underwent a 3cm medium length-wise laparotomy,exposure of the small intestine,identification and dissection of the SMA and then,closure abdominal cavity.The I/R group:the rats were operated by occlusion of SMA for 45 min,and then,same with control group. The edaravone group:the rats were operated by occlusion of SMA for 45 min, 5 min before reperfusion,inject edaravone through tail vein(3mg/kg),and then,same with I/R group.At the end of the operation,the rats were sacrificed,and dissected 10cm segment of ileum to determination of intestines mucous membrane's injury.The serum of TNF-α,IL-1β, IL-6,IL-10 are measured by ELISA.Cut tissues from liver and spleen at the same weight and portal vein blood to detect bacteria.
[Results](1)The changes of intestinal mucosa:In I/R group,the intestinal mucosa presented dilated and exposed capillaries and denuded villi,some of villi hemorrhage,ulceration.The lamina propria was edema and infiltrated with inflammatory cells.The intestinal mucosal structure maintain intact with lifting of the epithelial layer from the lamina propria and moderate extension of the subepithelial space in edaravone group.In edaravone group,histopathologic scores were significantly lower than that of I/R group.(2) Compared with Contraol group,the serum contents of TNF-α,IL-1β,IL-6 in I/R group,edaravone group are obviously higher, and the edaravone group is lower than that of I/R group.The contents of IL-10 in other two groups are lower than that of control group,and edaravone group are higher than that of I/R group.(3)Compared with control group, the bacteria transposition in I/R group,edaravone group is obviously higher,and the edaravone group is lower than that of I/R group.
[Conclusion]Edaravone can protects against small intestinal ischemia-reperfusion injury in rats.(1)Edaravone makes small intestinal mucosal damage degree alleviated in rat I/R injury.(2) Edaravone can reduce the contents of inflammatory TNF-α,IL-1β,IL-6 and promote the contents of anti-inflammatory medium Ih-10 in rat I/R injury.(3) Edaravone can reduce the bacterias transposition of small intestine in rat I/R ingury.
引文
[1]Sola A,Alfaro V,Pesguero J,et al.Co2 in static mesenteric venous blood during intestinal ischemia and ischemic preconditioning in rats[J].Shock,2001,16(5):403-408.
[2]Turnage RH,Ladesly KM.Rogers T,et al.Neutrophil regulation of splanchnic blood flow after hemorrhagic shock[J].Ann Surg.1995;222(1);66-72.
[3]Akgur FM,Olguner M,Yenici O,et al.The effect of allopurinol pretreatment on intestinal hypoperfusion encountered after correction of intestinal volvulus[J].J Pediatr Surg.1996;31(9):1205-1207.
[4]Tomatsuri N.Yoshida N,Takagt T,et al.Edaravone,a newly developed radical scavenge-protects against ischemia-reperfusion injury of the small intestine in rats[J],lnt J Mol Med,2004,13(1):105-109.
[5]Tanaka M.Pharmacological and clinical profile of the free radical scavenger edaravone as a neuro protective agent[J].Nippon Yakurigaku Zasshi,2002,119(5):301-308.
[6]Edaravone Acute Infarction Study Group.Effect of a novel free radical scavenger,edaravone(MCI-186),on acute brain infarction.Randomized,place be controlled,double-blind study at multicenters[J].Cerebrovasc Dis,2003,15(3):222-229.
[7]Hayashi T,Mori T,Sohmiya K,et al.Efficacy of edaravone,a free radical scavenger,on left ventricular function and structure in diabetes mellitus[J].J cardiovasc Dharmacol,2003,41(6):923.
[8]周庆玲,吴建文,方玉松,等.依达拉奉对肺缺血再灌注损伤保护作用的实验研究[J].山东大学学报,2007,45(2):130-134.
[9]Hiranuma S,Ito K,Noda Y,et al.Amelioration of hepatic ischemia-reperfusion injury in the remnant liver after partial hepatectomy in rats[J].J Gastroenterel Hepatol,2007,22(12):2167-2172.
[10]Mauyama M,Hayama T,Funao K,et al.Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model[J].Transplant Proc,2006,38(7):2199-2200.
[11]张浩,崔乃强.肠屏障与多器官功能障碍综合征[J].中国中西医结合外科杂志,2007,13(3):316-318.
[12]Xia ZY,Liu XY,Zhan LY,et al.Ginsenosides compound(shen fu)attenuates gastrointestinal injury and inhibits inflammatory response after cardiopulmonary bypass in patients with congenital heart disease[J].J Thorac Cardiovasc Surg,2005,130(2):258-264.
[13]Slater TF.Free radical mechanism in tissue injury[J].Biochem J,1984,222(1):1-15.
[14]Keley J,Hemontolor G,Younis W,et al.Mast cell activation by lipoproteins [J].Methods Mol Biol,2006,2(315):341-348.
[15]Orsenigo MN,Faelli A,POrta C,et al.Oxidative stress reduces trans intestinal transports and(Na+,K+)-ATPase activity in rat jejunum[J].Arch Biochem Biophys,2007,466(2):300-307.
[16]Mikawa K,Akamatsu H,Nishina K,et al.Effects of edaravone on human neutrophil function.Acta Anaesthesiol Scand,2005,49(3):385-389.
[17]Tabrizchi R.Edaravone Mitsubishi-Tokyo.Curr Opin Investing Drugs,2000,1(3):347-454.
[18]Fujise T,lwakiri R,Wu B,et al.Apoptotic pathway in the rat small intestinal.mucosa is different between fasting and ischemia-reperfusion[J].Am J Physiol Gastrointest Liver Physiol,2006,291(1):G110-6.
[19]Lozano FS,BarrosMB,FresnadilloMJ,et al.Nitric oxide prevents the bacterial translocation and inhibits the systemic inflammatory response produced by implantation of a vascular prosthesis followed by Zymosan A[J].Inf lamm Res,2005,54(6):261-270.
[20]Juranek I,Bezek S.Controversy of free radical hypothesis reactive oxygen species-cause or consequence of tissue injury?[J].Gen Physiol Biophys,2005,24(3):263-278.
[21]牛海静,王邦茂,肠黏膜屏障与功能[J].解剖与临床,2007,12(2):138-140.
[22]Hebra A Brown MF.MeGeehin K.et al.The effects of ischemia and reperfusion on intestinal motility.J Pediatr Surg,1993,28:362-366.
[23]Deitch EA.Bacterial translocation of the gut flora.J Trauma,1990,30:184-189.
[24]Remick DG,CallDR,Ebong SJ,et al.Combination immunotherapy with soluble tumor necrosis factor receptors plus interleukin 1 receptor antagonist decreases sep sis mortality[J].Crit Care Med,2001,29(3):473-481.
[25]Hotchkiss RS,Karl IE.The pathophysiology and treatment of sepsis[J].N Engl J Med,2003,348(2):138-150
[26]张树平,胡涛,栾海云,等.肠缺血再灌注大鼠肺及血液白细胞介素6、白细胞介素8和肿瘤坏死因子α变化与辅酶Q10的干预[J].中国组织工程研究与临床康复,2007,27(11):5429-5431.
[27]hrruda MJ,Poggetti RS,Fontes B,et al.Intestinal ischemia-reperfusion induces bronchial hyper activity and increases serum TNFα in rats[J].Clinics,2006,61(1):21-28.
[28]Raddatz D,Bockemuh]M.Ramadori G.Quantitative measurement of cytokine mRNA in inflammatory bowel disease:relation to clinical and endoscopic activity and outcome.Eur J Gastroenterol Hepatol,2005,17:547-557.
[29]Zhang JX,Dang SC,Qu JG,et al.Changes of gastric and intestinal blood flow,serum phospholipase A2 and interleukin-1β in rats with acute necrotizing pancreatitis.WOrld J Gastroenterol,2005,11,3578-3581.
[30]Spittler A,Razenberger M,Kupper H,el al.Relationship between interleukin —6 plasma concentration in patients with sepsis,monocyte phenotype,monocyte phagocytic properties,and cytokine production[J].Clin Infect Dis,2000,31(6):1338-1420.
[31]Patel RT,Deen KI,Youngs D,et al.Interleukin 6 is a prognostic indicator of outcome in severe intra abdominal sepsis[J].Br J Surg,1994,81:1306-1308.
[32]张丰,曹苇.肿瘤坏死因子白细胞介素-6和脓毒症[J].国外医学·外科学分册,2005,32(2):146-149.
[33]Yang XM,ProctorJB,Cui L,et al.Multiple brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J].Amcol l Cardid,2004;4(5):1103-1110.
[34]孙凯,刘志苏,孙权.缺血后处理对肝脏缺血/再灌注损伤的保护作用[J].武汉大学学 报, 2004 25 (2): 104-107.
[35] Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells[J]..Cancer Res,. 2001, 61(4): 1659-1665.
[36] Mrtrailler-Ruehonnet I, Pagano A , Cameseeehi S, et al. Bel-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria- dependent pathway[J]. Free Radie Biol Med, 2007; 42(7): 1062-1074.
[37] Anker P, Lyautey J, Lederrey C, et al. Circulating nucleic acids in plasma or serum[J]. Clin Chim Acta, 2001, 313 (12): 143-146.
[38] Sher Y P, Shih J Y, Yang P C, et al. Prognosis of non—small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes[J]. Clin Cancer Res, 2005, 11(1): 173-179.
[1]Thurman JM.Triggers of inflammation after renal ischemia-reperfusion[J].Clin Immunol,2007,12312(1):7-13.
[2]Tugtepe H,Sener G,Biyikli NK,et al.The protective effect,of oxytocin on renal ischemia/reperfusion injury in rats[J].Regul Pept,2007,14114(1):101-108.
[3]Sargis R M,Subbaiah P V.Protection of membrane cholesterol by sphingomyelin against free radical-mediated oxidation[J].2006,40(12):2092-2102.
[4]Janisch K M,Milde J,Schempp HT,et al.Vitamin C,vitamin E and flavonoids[J].Dev Ophthaimol,2005,38(17):59-69.
[5]Juranek I,Bezek S.Controversy of free radical hypothesis;reactiveoxygen species-cause or consequence of tissue injury?[J]. Gen Physiol Biophys, 2005, 24(3): 263-278
[6] Stadtman E R, Levine R L. Free radical-mediated oxidation of free amino acids and amino acid residues in proteins[J]. Amino Acids, 2003, 25(3-4):207-218.
[7] Conn KJ, Ullman MD, Eisenhauer PB, et al. Decreased expression of the NADH: ubiquinone oxidoreductase(complex 1)subunit 4 in 1-methyl-4-phenylpyridinium- treated human neuroblastoma SH-SY5Y cells[J]. Neurosci Lett, 2001, 306(3):145- 148.
[8] Juranek I,Bezek S. Controversy of free radical hypothesis, reactive oxygen species-cause or consequence of tissue injury?[J]. Gen Physiol Biophys, 2005, 24 (3): 263-278.
[9] Fagan JM, Sleczka B G, Sohar I. Quantitation of oxidative damage to tissue protein[J]. Int J Biochem CellBiol, 1999, 31(7):751-757.
[10] Stadtman E R, Levine R L.Free radical-mediated oxidation of free amino acids and amino acid residues in proteins[J]. Amino Acids, 2003, 25(3-4):207-218.
[11] Jeannette VV, Kalyanaraman B, Mary CK. Mitochondrial aconitase is a source of hydroxyl. radical[J].J Biol Chem, 2000, 275(19):14064-14069.
[12] Lounsbury KM, Hu Q, Ziegelstein RC. Calcium signaling and oxidant stress in the vasculature[J]. Free Radical Biology Med, 2000, 28(9): 1362-1369.
[13] Grace PA. Ischemia reperfusion injury. Br J Surg, 1994, 81(5):637-647.
[14] Allen RG, Tresini M. Oxidative stress and gene regulation[J]. Free Radic Biol Med, 2000,28(3):463-499.
[15] Masutani H. Oxidative stress response and signaling in ematological malignancies and HIV infection[J]. Int J Hematol, 2000,71(1);25-32.
[16] Natarajan V, Scribner WM, Al-Hassani M. Reactive oxygen species signaling throngh regulation of protein tyrosine phosphorylation in endothelial cells [J]. Environ Health Perspect, 1998,106(5):1205-1212.
[17] Piantadosi CA , Zhang I. Mitochondrial generatiqn of reactive oxygen species after brain ischemia in the rat[J]. Stroke,1996, 27(2):327-331.
[18] Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals[J].Faseb J,2000,14(2):312-318.
[19]Kohno S,Miyajima H,Takahashi Y,et al.Defective electron transfer in complexes Ⅰ and Ⅳ in patients with aceruloplasminemia[J].J Neurol Sci,2000,182(1):57-60.
[20]Boya P,Roques B,Kroemer G.New EMBO members' review:viral and bacterial proteins regulating apoptosis at the mitochondriat level[J].EMBO J,2001,20(16):4325-4331.
[21]徐建兴.呼吸链电子漏在细胞调亡中的作用[J].生物化学与生物物理进展,2003,30(4):29-35。
[22]Akgur FM,Olguner M,Yenici O,et al.The effect of allopurino]pretreatment on intestinal hypoperfusion encountered after correction of intestinal volvulus [J].J Pediatr Surg,1996,31(9):1205.
[23]Kojima M,Iwakiri R,Wu B,et al.Effects of antioxidative agents on apoptosis induced by ischaemia-reperfusion in rat intestinal mucosa[J].Aliment Pharmacol Ther,2003,18(1):139-145.
[24]Tomatsuri N,Yoshida N,Takagi T,et al.Edaravone,a newly developed radical scavenge,protects against ischemia-reperfusion injury of the small intestine in rats[J].Int J Mol Med,2004,13(1):105-109.
[2]Turnage RH,Ladesly KM.Rogers T,et al.Neutrophil regulation of splanchnic blood flow after hemorrhagic shock[J].Ann Surg.1995;222(1);66-72.
[3]Akgur FM,Olguner M,Yenici O,et al.The effect of allopurinol pretreatment on intestinal hypoperfusion encountered after correction of intestinal volvulus[J].J Pediatr Surg.1996;31(9):1205-1207.
[4]Tomatsuri N.Yoshida N,Takagt T,et al.Edaravone,a newly developed radical scavenge-protects against ischemia-reperfusion injury of the small intestine in rats[J],lnt J Mol Med,2004,13(1):105-109.
[5]Tanaka M.Pharmacological and clinical profile of the free radical scavenger edaravone as a neuro protective agent[J].Nippon Yakurigaku Zasshi,2002,119(5):301-308.
[6]Edaravone Acute Infarction Study Group.Effect of a novel free radical scavenger,edaravone(MCI-186),on acute brain infarction.Randomized,place be controlled,double-blind study at multicenters[J].Cerebrovasc Dis,2003,15(3):222-229.
[7]Hayashi T,Mori T,Sohmiya K,et al.Efficacy of edaravone,a free radical scavenger,on left ventricular function and structure in diabetes mellitus[J].J cardiovasc Dharmacol,2003,41(6):923.
[8]周庆玲,吴建文,方玉松,等.依达拉奉对肺缺血再灌注损伤保护作用的实验研究[J].山东大学学报,2007,45(2):130-134.
[9]Hiranuma S,Ito K,Noda Y,et al.Amelioration of hepatic ischemia-reperfusion injury in the remnant liver after partial hepatectomy in rats[J].J Gastroenterel Hepatol,2007,22(12):2167-2172.
[10]Mauyama M,Hayama T,Funao K,et al.Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model[J].Transplant Proc,2006,38(7):2199-2200.
[11]张浩,崔乃强.肠屏障与多器官功能障碍综合征[J].中国中西医结合外科杂志,2007,13(3):316-318.
[12]Xia ZY,Liu XY,Zhan LY,et al.Ginsenosides compound(shen fu)attenuates gastrointestinal injury and inhibits inflammatory response after cardiopulmonary bypass in patients with congenital heart disease[J].J Thorac Cardiovasc Surg,2005,130(2):258-264.
[13]Slater TF.Free radical mechanism in tissue injury[J].Biochem J,1984,222(1):1-15.
[14]Keley J,Hemontolor G,Younis W,et al.Mast cell activation by lipoproteins [J].Methods Mol Biol,2006,2(315):341-348.
[15]Orsenigo MN,Faelli A,POrta C,et al.Oxidative stress reduces trans intestinal transports and(Na+,K+)-ATPase activity in rat jejunum[J].Arch Biochem Biophys,2007,466(2):300-307.
[16]Mikawa K,Akamatsu H,Nishina K,et al.Effects of edaravone on human neutrophil function.Acta Anaesthesiol Scand,2005,49(3):385-389.
[17]Tabrizchi R.Edaravone Mitsubishi-Tokyo.Curr Opin Investing Drugs,2000,1(3):347-454.
[18]Fujise T,lwakiri R,Wu B,et al.Apoptotic pathway in the rat small intestinal.mucosa is different between fasting and ischemia-reperfusion[J].Am J Physiol Gastrointest Liver Physiol,2006,291(1):G110-6.
[19]Lozano FS,BarrosMB,FresnadilloMJ,et al.Nitric oxide prevents the bacterial translocation and inhibits the systemic inflammatory response produced by implantation of a vascular prosthesis followed by Zymosan A[J].Inf lamm Res,2005,54(6):261-270.
[20]Juranek I,Bezek S.Controversy of free radical hypothesis reactive oxygen species-cause or consequence of tissue injury?[J].Gen Physiol Biophys,2005,24(3):263-278.
[21]牛海静,王邦茂,肠黏膜屏障与功能[J].解剖与临床,2007,12(2):138-140.
[22]Hebra A Brown MF.MeGeehin K.et al.The effects of ischemia and reperfusion on intestinal motility.J Pediatr Surg,1993,28:362-366.
[23]Deitch EA.Bacterial translocation of the gut flora.J Trauma,1990,30:184-189.
[24]Remick DG,CallDR,Ebong SJ,et al.Combination immunotherapy with soluble tumor necrosis factor receptors plus interleukin 1 receptor antagonist decreases sep sis mortality[J].Crit Care Med,2001,29(3):473-481.
[25]Hotchkiss RS,Karl IE.The pathophysiology and treatment of sepsis[J].N Engl J Med,2003,348(2):138-150
[26]张树平,胡涛,栾海云,等.肠缺血再灌注大鼠肺及血液白细胞介素6、白细胞介素8和肿瘤坏死因子α变化与辅酶Q10的干预[J].中国组织工程研究与临床康复,2007,27(11):5429-5431.
[27]hrruda MJ,Poggetti RS,Fontes B,et al.Intestinal ischemia-reperfusion induces bronchial hyper activity and increases serum TNFα in rats[J].Clinics,2006,61(1):21-28.
[28]Raddatz D,Bockemuh]M.Ramadori G.Quantitative measurement of cytokine mRNA in inflammatory bowel disease:relation to clinical and endoscopic activity and outcome.Eur J Gastroenterol Hepatol,2005,17:547-557.
[29]Zhang JX,Dang SC,Qu JG,et al.Changes of gastric and intestinal blood flow,serum phospholipase A2 and interleukin-1β in rats with acute necrotizing pancreatitis.WOrld J Gastroenterol,2005,11,3578-3581.
[30]Spittler A,Razenberger M,Kupper H,el al.Relationship between interleukin —6 plasma concentration in patients with sepsis,monocyte phenotype,monocyte phagocytic properties,and cytokine production[J].Clin Infect Dis,2000,31(6):1338-1420.
[31]Patel RT,Deen KI,Youngs D,et al.Interleukin 6 is a prognostic indicator of outcome in severe intra abdominal sepsis[J].Br J Surg,1994,81:1306-1308.
[32]张丰,曹苇.肿瘤坏死因子白细胞介素-6和脓毒症[J].国外医学·外科学分册,2005,32(2):146-149.
[33]Yang XM,ProctorJB,Cui L,et al.Multiple brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J].Amcol l Cardid,2004;4(5):1103-1110.
[34]孙凯,刘志苏,孙权.缺血后处理对肝脏缺血/再灌注损伤的保护作用[J].武汉大学学 报, 2004 25 (2): 104-107.
[35] Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells[J]..Cancer Res,. 2001, 61(4): 1659-1665.
[36] Mrtrailler-Ruehonnet I, Pagano A , Cameseeehi S, et al. Bel-2 protects against hyperoxia-induced apoptosis through inhibition of the mitochondria- dependent pathway[J]. Free Radie Biol Med, 2007; 42(7): 1062-1074.
[37] Anker P, Lyautey J, Lederrey C, et al. Circulating nucleic acids in plasma or serum[J]. Clin Chim Acta, 2001, 313 (12): 143-146.
[38] Sher Y P, Shih J Y, Yang P C, et al. Prognosis of non—small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes[J]. Clin Cancer Res, 2005, 11(1): 173-179.
[1]Thurman JM.Triggers of inflammation after renal ischemia-reperfusion[J].Clin Immunol,2007,12312(1):7-13.
[2]Tugtepe H,Sener G,Biyikli NK,et al.The protective effect,of oxytocin on renal ischemia/reperfusion injury in rats[J].Regul Pept,2007,14114(1):101-108.
[3]Sargis R M,Subbaiah P V.Protection of membrane cholesterol by sphingomyelin against free radical-mediated oxidation[J].2006,40(12):2092-2102.
[4]Janisch K M,Milde J,Schempp HT,et al.Vitamin C,vitamin E and flavonoids[J].Dev Ophthaimol,2005,38(17):59-69.
[5]Juranek I,Bezek S.Controversy of free radical hypothesis;reactiveoxygen species-cause or consequence of tissue injury?[J]. Gen Physiol Biophys, 2005, 24(3): 263-278
[6] Stadtman E R, Levine R L. Free radical-mediated oxidation of free amino acids and amino acid residues in proteins[J]. Amino Acids, 2003, 25(3-4):207-218.
[7] Conn KJ, Ullman MD, Eisenhauer PB, et al. Decreased expression of the NADH: ubiquinone oxidoreductase(complex 1)subunit 4 in 1-methyl-4-phenylpyridinium- treated human neuroblastoma SH-SY5Y cells[J]. Neurosci Lett, 2001, 306(3):145- 148.
[8] Juranek I,Bezek S. Controversy of free radical hypothesis, reactive oxygen species-cause or consequence of tissue injury?[J]. Gen Physiol Biophys, 2005, 24 (3): 263-278.
[9] Fagan JM, Sleczka B G, Sohar I. Quantitation of oxidative damage to tissue protein[J]. Int J Biochem CellBiol, 1999, 31(7):751-757.
[10] Stadtman E R, Levine R L.Free radical-mediated oxidation of free amino acids and amino acid residues in proteins[J]. Amino Acids, 2003, 25(3-4):207-218.
[11] Jeannette VV, Kalyanaraman B, Mary CK. Mitochondrial aconitase is a source of hydroxyl. radical[J].J Biol Chem, 2000, 275(19):14064-14069.
[12] Lounsbury KM, Hu Q, Ziegelstein RC. Calcium signaling and oxidant stress in the vasculature[J]. Free Radical Biology Med, 2000, 28(9): 1362-1369.
[13] Grace PA. Ischemia reperfusion injury. Br J Surg, 1994, 81(5):637-647.
[14] Allen RG, Tresini M. Oxidative stress and gene regulation[J]. Free Radic Biol Med, 2000,28(3):463-499.
[15] Masutani H. Oxidative stress response and signaling in ematological malignancies and HIV infection[J]. Int J Hematol, 2000,71(1);25-32.
[16] Natarajan V, Scribner WM, Al-Hassani M. Reactive oxygen species signaling throngh regulation of protein tyrosine phosphorylation in endothelial cells [J]. Environ Health Perspect, 1998,106(5):1205-1212.
[17] Piantadosi CA , Zhang I. Mitochondrial generatiqn of reactive oxygen species after brain ischemia in the rat[J]. Stroke,1996, 27(2):327-331.
[18] Barja G, Herrero A. Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals[J].Faseb J,2000,14(2):312-318.
[19]Kohno S,Miyajima H,Takahashi Y,et al.Defective electron transfer in complexes Ⅰ and Ⅳ in patients with aceruloplasminemia[J].J Neurol Sci,2000,182(1):57-60.
[20]Boya P,Roques B,Kroemer G.New EMBO members' review:viral and bacterial proteins regulating apoptosis at the mitochondriat level[J].EMBO J,2001,20(16):4325-4331.
[21]徐建兴.呼吸链电子漏在细胞调亡中的作用[J].生物化学与生物物理进展,2003,30(4):29-35。
[22]Akgur FM,Olguner M,Yenici O,et al.The effect of allopurino]pretreatment on intestinal hypoperfusion encountered after correction of intestinal volvulus [J].J Pediatr Surg,1996,31(9):1205.
[23]Kojima M,Iwakiri R,Wu B,et al.Effects of antioxidative agents on apoptosis induced by ischaemia-reperfusion in rat intestinal mucosa[J].Aliment Pharmacol Ther,2003,18(1):139-145.
[24]Tomatsuri N,Yoshida N,Takagi T,et al.Edaravone,a newly developed radical scavenge,protects against ischemia-reperfusion injury of the small intestine in rats[J].Int J Mol Med,2004,13(1):105-109.