曲美他嗪降低大鼠脂肪肝缺血再灌注损伤的研究

摘要

目的：探讨曲美他嗪（TMZ）对自体肝移植大鼠脂肪肝缺血再灌注损伤的保护作用。方法30只Wistar大鼠喂食高脂饲料诱导脂肪肝模型后，随机分为假手术（Sham）组、模型（Model）组和TMZ组，每组10只。采用脂肪肝大鼠自体肝移植缺血再灌注损伤模型，于再灌注6 h后取材，分别观察血浆丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肝组织丙二醛（MDA）、超氧化物歧化酶（SOD）水平以及肝组织病理情况。Western blot法检测肝组织Bcl-2、Caspase-3的表达水平；TUNEL法检测肝细胞凋亡情况。结果术后6 h，与Model组相比，TMZ组血浆ALT、AST、肝组织MDA含量明显降低（P<0.05），肝组织SOD含量增高（P<0.05）。TMZ组肝组织中Bcl-2的表达水平明显高于Model组，而活化的Caspase-3的水平明显降低（P<0.05）。肝组织HE染色及TUNEL显示TMZ组肝细胞水肿、肝窦狭窄及肝细胞凋亡明显轻于Model组。结论在缺血再灌注时，TMZ减少氧化应激，促进Bcl-2表达，抑制Caspase-3的活化，减少肝细胞凋亡，对大鼠脂肪肝缺血再灌注损伤起保护作用。%Objective To investigate the protective effects of Trimetazidine(TMZ)on the ischemia reperfusion injury (IRI)of fatty liver in autotransplantation model. Methods Fatty liver model was established by feeding high fat diet. Male Wistar rats (n=30) were randomized into three groups;Sham group, TMZ group and Model group. Liver was autotransplanted in both TMZ group and Model group. Serum levels of ALT, SOD, MDA, Bcl-2 and activated Caspase-3 were assessed 6 hours after the operation. The pathological performances of liver were also determined. Results Compared with the Model group, serum levels of ALT,AST, MDA and SOD levels decreased significantly in the TMZ group(P<0.05). Serum level of Bcl-2 was higher while level of activated Caspase-3 was lower in TMZ group than those in Model group(P<0.05). Histo⁃logical assay and TUNEL staining showed reduced hepatocyte swelling and narrowed sinusoid as well as decreased hepatic apoptosis in TMZ group compared with Model group. Conclusion TMZ can reduce oxidative stress, promote the expression of Bcl-2 and inhibit the activation of Caspase-3, which all contribute to its protective effect on fatty liver with ischemia-re⁃perfusion injury.