粉防己碱预处理减轻大鼠肝脏缺血再灌注损伤的机制研究

目的研究粉防己碱（tetrandrine,TET）预处理对大鼠肝缺血再灌注损伤的预防作用及其机制。方法大鼠肝脏左中叶缺血50 min,再灌注24 h后处死（I/R组）,TET＋I/R组缺血前30 min腹腔注射TET（50 mg/kg）,余同I/R组。大鼠处死前采血检测丙氨酸氨基转移酶（ALT）,天门冬氨酸氨基转移酶（AST）,乳酸脱氢酶（LDH）,取缺血肝组织进行超氧化物歧化酶（SOD）,一氧化氮（NO）,丙二醛（MDA）,湿重干重（W/D）比检测和组织学检查。结果I/R组血清ALT,AST和LDH升高,组织MDA水平,W/D比值也明显升高,SOD活性和NO含量下降。在TET＋I/R组,血清ALT,AST,LDH,以及组织W/D比值较I/R组降低,SOD活性和NO含量升高。此外,TET＋I/R组大鼠血清ALT,AST,组织MDA和W/D比值较假手术组升高,SOD活性和NO含量降低.组织学检查显示TET＋I/R组肝损害减轻。结论TET能减轻但不能防止肝I/R损伤的发生,减少脂质过氧化物产生是TET抗I/R损伤的原因之一。

Effect of pharmacologic preconditioning with tetrandrine on subsequent ischemia/reperfusion injury in rat liver

Objective The effect of tetrandrine(TET)pretreatment of Wistar rats subjected to warm hepatic ischemia/reperfusion(I/R)was investigated.Metheds After 50 minutes of ischemia in the left and median lobes of the liver and 24 hours of reperfusion(I/R group),the rats were killed.The TET I/R group rats were pretreated with TET(50 mg/kg body weight IP)30 minutes prior to the onset of ischemia.Blood samples were taken for measurement of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH).Tissue was taken from the ischemic lobes for measurement of superoxide dismutase(SOD),malonyldialdehyde(MDA),and myeloperoxidase(MPO);determination of the wet/dry weight(W/D)ratio;and histologic studies.Results The results showed that ALT,AST,and LDH levels in serum were increased in the I/R group;tissue MDA generation,MPO activity,and the W/D ratio were also increased,accompanied by decreased SOD activity.The serum ALT,AST,and LDH levels,as well as the tissue MPO level and W/D ratio,were lower in the TET I/R group than in the I/R group;and the SOD level was higher in the TET IR group than in the I/R group.Moreover,the serum ALT and AST,tissue MDA,and W/D ratio in the TET I/R group were higher,and the SOD was lower than in the sham group.The histologic examination showed protection against liver damage in the TET I/R group.Conclusion The results demonstrated that pretreatment with TET could somewhat protect the liver against I/R injury but does not prevent it.The simultaneous decrease of both lipid peroxide generation and polymorphonuclear neutrophil infiltration in the ischemic liver may explain the acquisition of tolerance following administration of TET.