远端缺血预处理对缺血再灌注后肾功能的保护
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摘要
目的观察在动物模型中远端缺血预处理(RIPC)对缺血再灌注后肾功能是否有保护作用。方法将雄性SD大鼠24只随机分成4组各6只:空白组,缺血再灌注组,早期RIPC组,晚期RIPC组。空白组仅分离左右肾蒂及肾周组织,45min后关腹;缺血灌注组于大鼠右下肢置松弛止血带30min后分离左右肾蒂和肾周组织,切除右肾并夹闭左肾蒂45min后复灌;早RIPC组和晚RIPC组先行30min RIPC后,两者分别于即刻和24h后采取同缺血灌注组措施。术后24h检测血肌酐(Cr)、尿素氮(BUN),取左肾组织行HE染色病理分析和检测髓过氧化物酶(MPO)、丙二醛(MDA)和超氧化物歧化酶(SOD)。结果缺血灌注组、早RIPC组和晚RIPC组术后24h的Cr、BUN、MPO、MDA、SOD和病理评分各项指标均显著升高(P<0.05)。与缺血灌注组相比,早RIPC组和晚RIPC组有显著保护效果,且晚RIPC组保护效果较早RIPC组好(P<0.05)。结论 RIPC可为缺血再灌注后肾功能提供保护,且晚期保护窗作用较明显,其机制可能与降低氧化应激反应、抑制炎性细胞浸润有关。
Objective To investigate whether remote ischemic preconditioning(RIPC)provides renal protection after ischemia reperfusion injury in animal model.Methods A total of 24 rats were equally divided into four groups:sham group,ischemia reperfusion group(IR group),acute RIPC group,and delayed RIPC group.Sham group received a sham operation;IR group had a right nephrectomy immediately following a 45 min ischemia by applying microvascular on left kidney;acute RIPC group accepted RIPC before surgery;delayed RIPC group received RIPC24 h earlier.Cr,BUN,MPO,MDA,SOD and tubular score were measured 24 h after ischemia reperfusion.Results The levels of Cr,BUN,MPO,MDA,SOD and tubular score were significantly increased in IR,acute RIPC and delayed RIPC groups.Compared with IR group,acute RIPC group and delayed RIPC group had better renal protection,and the delayed group achieved more(P<0.05).Conclusion RIPC can offer protection for kidney suffering IRI and the effect of delayed RIPC is more obvious,for RIPC may suppress the oxidative stress reaction and inhibit inflammatory cell infiltration.
Objective To investigate whether remote ischemic preconditioning(RIPC)provides renal protection after ischemia reperfusion injury in animal model.Methods A total of 24 rats were equally divided into four groups:sham group,ischemia reperfusion group(IR group),acute RIPC group,and delayed RIPC group.Sham group received a sham operation;IR group had a right nephrectomy immediately following a 45 min ischemia by applying microvascular on left kidney;acute RIPC group accepted RIPC before surgery;delayed RIPC group received RIPC24 h earlier.Cr,BUN,MPO,MDA,SOD and tubular score were measured 24 h after ischemia reperfusion.Results The levels of Cr,BUN,MPO,MDA,SOD and tubular score were significantly increased in IR,acute RIPC and delayed RIPC groups.Compared with IR group,acute RIPC group and delayed RIPC group had better renal protection,and the delayed group achieved more(P<0.05).Conclusion RIPC can offer protection for kidney suffering IRI and the effect of delayed RIPC is more obvious,for RIPC may suppress the oxidative stress reaction and inhibit inflammatory cell infiltration.
引文
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[13]KWIECIEN S,JASNOS K,MAGIEROWSKI M,et al.Lipid peroxidation,reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress-induced gastric injury[J].J Physiol Pharmacol,2014,65(5):613-622.
[14]BEN BAOUALI A,AUBE H,MAUPOIL V,et al.Plasma lipid peroxidation in critically ill patients:importance of mechanical ventilation[J].Free Radic Biol Med,1994,16(2):223-227.
[15]HAEGENS A,VERNOOY J H,HEERINGA P,et al.Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents[J].Eur Respir J,2008,31(2):252-260.
[16]DOW J,BHANDARI A,SIMKHOVICH B Z,et al.The effect of acute versus delayed remote ischemic preconditioning on reperfusion induced ventricular arrhythmias[J].J Cardiovasc Electrophysiol,2012,23(12):1374-1383.
[17]SHIAB F S.Preconditioning:from experimental findings to novel therapies in acute kidney injury[J].Minerva Urol Nefrol,2009,61(3):143-157.
[18]ONG S G,HAUSENLOY D J.Hypoxia-inducible factor as a therapeutic target for cardioprotection[J].Pharmacol Ther,2012,136(1):69-81.
[2]PRZYKLENK K,BAUER B,OVIZE M,et al.Regional ischemic‘preconditioning’protects remote virgin myocardium from subsequent sustained coronary occlusion[J].Circulation,1993,87(3):893-899.
[3]TAKAOKA A,NAKAE I,MITSUNAMI K,et al.Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits:effects of“remote preconditioning”[J].J Am Coll Cardiol,1999,33(2):556-564.
[4]GHO B C,SCHOEMAKER R G,VAN DEN DOEL M A,et al.Myocardial protection by brief ischemia in noncardiac tissue[J].Circulation,1996,94(9):2193-2200.
[5]OXMAN T,ARAD M,KLEIN R,et al.Limb ischemia preconditions the heart against reperfusion tachyarrhythmia[J].Am J Physiol,1997,273(4Pt 2):H1707-1712.
[6]BOLLI R.The late phase of preconditioning[J].Circ Res,2000,87(11):972-983.
[7]TRIALISTS G,HEALY D A,KHAN W A,et al.Remote preconditioning and major clinical complications following adult cardiovascular surgery:systematic review and meta-analysis[J].Int J Cardiol,2014,176(1):20-31.
[8]YANG Y,LANG X B,ZHANG P,et al.Remote ischemic preconditioning for prevention of acute kidney injury:a meta-analysis of randomized controlled trials[J].Am J Kidney Dis,2014,64(4):574-583.
[9]TAPURIA N,KUMAR Y,HABIB M M,et al.Remote ischemic preconditioning:a novel protective method from ischemia reperfusion injury-a review[J].J Surg Res,2008,150(2):304-330.
[10]PALLER M S,HOIDAL J R,FERRIS T F.Oxygen free radicals in ischemic acute renal failure in the rat[J].J Clin Invest,1984,74(4):1156-1164.
[11]YURDAKUL T,KULAKSIZOGLU H,PISKIN M M,et al.Combination antioxidant effect of alpha-tocoferol and erdosteine in ischemia-reperfusion injury in rat model[J].Int Urol Nephrol,2010,42(3):647-655.
[12]WU J Q,KOSTEN T R,ZHANG X Y.Free radicals,antioxidant defense systems,and schizophrenia[J].Prog Neuropsychopharmacol Biol Psychiatry,2013,46:200-206.
[13]KWIECIEN S,JASNOS K,MAGIEROWSKI M,et al.Lipid peroxidation,reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress-induced gastric injury[J].J Physiol Pharmacol,2014,65(5):613-622.
[14]BEN BAOUALI A,AUBE H,MAUPOIL V,et al.Plasma lipid peroxidation in critically ill patients:importance of mechanical ventilation[J].Free Radic Biol Med,1994,16(2):223-227.
[15]HAEGENS A,VERNOOY J H,HEERINGA P,et al.Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents[J].Eur Respir J,2008,31(2):252-260.
[16]DOW J,BHANDARI A,SIMKHOVICH B Z,et al.The effect of acute versus delayed remote ischemic preconditioning on reperfusion induced ventricular arrhythmias[J].J Cardiovasc Electrophysiol,2012,23(12):1374-1383.
[17]SHIAB F S.Preconditioning:from experimental findings to novel therapies in acute kidney injury[J].Minerva Urol Nefrol,2009,61(3):143-157.
[18]ONG S G,HAUSENLOY D J.Hypoxia-inducible factor as a therapeutic target for cardioprotection[J].Pharmacol Ther,2012,136(1):69-81.