缺血后适应减轻急性下肢缺血再灌注损伤的实验研究

目的 观察缺血后适应(IPC)减轻急性下肢缺血(AU)再灌注损伤的疗效并探讨其机制.方法 将45只新西兰大白兔采用高脂饮食与动脉内膜球囊损伤结合的方式建立下肢动脉粥样硬化狭窄动物模型,随机分为对照组、缺血再灌注组(IR组)、缺血后适应组(IPC组),每组各15只.检测三组大白兔阻断股动脉前、持续再灌注2h后血液中肌酸激酶(CK)、丙二醛(MDA)、超氧化物岐化酶(SOD)水平,观察再灌注后下肢骨骼肌组织学改变,并采用原位末端标记法(TUNEL)分析三组大白兔下肢再灌注后骨骼肌细胞凋亡情况.结果 与IR组比较,IPC组兔血浆CK、MDA明显降低(7.49±0.84) U/L与(8.19±1.06) U/L,P＜0.05],(3.67±0.36) nmol/L与(4.06±0.55) nmol/L,P＜0.05],而SOD则显著升高(420.40±30.94)μmol/L与(384.73±44.12) μmol/L,P＜0.05],骨骼肌细胞凋亡指数降低(12.27±2.11)％与(16.62±1.44)％,P＜0.01],差异有统计学意义,并且组织形态学观察IPC组兔骨骼肌损伤、坏死程度较IR组减轻.结论 急性下肢缺血应用IPC能显著减轻下肢缺血再灌注损伤,其机制与减少自由基生成、增强抗氧化及减轻缺血再灌注诱导的骨骼肌细胞凋亡有关.

Effects of ischemia postconditioning in reducing ischemia reperfusion injury in acute limp ischemia

Objective To study the effects of ischemia postconditioning（IPC） in reducing ischemia-reperfusion injury（IRI） in acute limp ischemia（ALI） and investigate the mechanism.Methods 45 New Zealand rabbits were treated with the method that combined high lipid diets and femoral intima injury by balloon inflation to build up limp atherosclerotic stenosis model,then they were randomly divided into three groups（each group 15 rabbits）：control group;IR group and IPC group.Serum creatine phosphate kinase（CK）,malondialehyde（MDA）,superoxide dismutase（SOD） in three groups were measured before occlusion and 2 hours after sustaining reperfusion.The histological changes of limp skeletal muscle of experimental rabbits were analyzed and TUNEL method was used to access apoptosis of skeletal muscle cells.Results The levels of CK,MDA in IPC group were lower than IR group［（7.49±0.84） vs （8.19±1.06）,P＜0.05］,［（3.67±0.36） vs （4.06±0.55）,P＜0.05］ while SOD level was higher than IR group［（420.40±30.94） vs （384.73±44.12）,P＜0.05］;The injury of skeletal muscles in IPC group was lighter than IR group and the apoptosis index of skeletal muscle cells was significantly decreased compared with that in IR group［（12.27±2.11）% vs （16.62±1.44）%,P＜0.01］.Conclusion Applying IPC in acute limp ischemia could alleviate IRI and protect skeletal muscles.The mechanism was associated with oxidation resistance enhancing and the effects in reducing apoptosis of skeletal muscles induced by IRI.