苦参碱对大鼠小体积肝移植缺血再灌注损伤的保护作用

Protective effect of matrine against ischemia and reperfusion injury in rat partial liver transplantation

目的:探讨苦参碱对大鼠小体积肝移植缺血再灌注损伤的保护作用及机制.方法:采用大鼠30%小体积肝移植模型,♂SD大鼠322只随机分为假手术组、小体积肝移植对照组和高、低剂量苦参碱治疗组(60、40mg/kg).观察术后1wk生存率,检测移植术2h、4h、1d、2d、3d、7d后ALT、AST及LDH值.光镜及电镜下评估移植肝病理形态学改变,ELISA法检测肝脏IL-6,TNF-α表达.结果:与对照组比较,苦参碱高、低剂量治疗组术后1wk生存率显著增加(80%,70%vs50%,均P<0.05),术后2h、4h、1dALT、AST及LDH明显降低(P<0.01).苦参碱治疗组中肝细胞和肝窦内皮细胞凋亡减少、细胞形态明显改善,苦参碱治疗组术后2h、4h、1d肝脏组织中IL-6,TNF-α水平明显降低(P<0.01).结论:苦参碱可减轻肝细胞及肝窦内皮细胞的损伤,改善小体积肝移植术后缺血再灌注损伤,其机制可能与苦参碱抑制肝移植术后IL-6、TNF-α等炎症因子的释放有关.

AIM： To investigate the protective effect of matrine against ischemia and reperfusion injury in rats with partial liver transplantation. METHODS： Using the 30% small-for-size liver transplantation （SLT） model, 322 male SD rats were randomly divided into sham operation group, SLT group, SLT＋low-dose matrine （40 mg/ kg） group and SLT＋high-dose matrine （80 mg/kg） group. Serum samples were collected to measure the levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and lactate dehydrogenase （LDH） at 2 h, 4 h, 1 d, 2 d, 3 d and 7 d after reperfusion of the portal vein. The one-week survival rate was observed in each group. Tissue samples were collected for observation of the morphologic changes under optical and electron microscope and detection of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） expression using enzyme-linked immunosorbent assay （ELISA）. RESULTS： In comparison with those in the SLT group, the one-week survival rates were increased markedly in the low- and high-dose matrine treatment groups （80%, 70% vs 50%, both P 〈 0.05）. The levels of ALT, AST and LDH as well as the expression of IL-6 and TNF-a were decreased significantly in the low- and highdose matrine treatment groups at 2 h, 4 h, and 1 d post-transplantation. The rats in matrinetreated groups showed reduced severity of ultrastructural changes in both hepatic cells and sinusoidal endothelial cells （SEC）. CONCLUSION： Matrine can prevent hepatic cells and SEC from ischemia and reperfusion injury during partial liver transplantation in rats, and the mechanism is associated with the release inhibition of inflammatory cytokines such as IL-6 and TNF-α.