天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (12): 1382-1385.doi: 10.11958/j.issn.0253-9896.2015.12.010

• 实验研究 • 上一篇    下一篇

曲美他嗪降低大鼠脂肪肝缺血再灌注损伤的研究

王腾飞1，杨涛2△，张威2，方振宇2，王洪海2，刘蕾2，张海明2，王玉亮3   

  1. 1 天津医科大学一中心临床学院（邮编300192）；2 天津市第一中心医院器官移植中心；3 卫生部危重病急救医学重点实验室
  • 收稿日期:2015-08-03 修回日期:2015-08-21 出版日期:2015-12-15 发布日期:2015-12-11
  • 通讯作者: △通讯作者E-mail：yangtao5588@medmail.com.cn E-mail:tengfeiwang6312@163.com
  • 作者简介:王腾飞（1988），男，硕士研究生在读，主要从事肝移植及肝胆外科研究
  • 基金资助:
    天津市卫生局科技基金资助项目（2011KZ30）；卫生公益性行业科研专项（201302009）；国家高技术研究发展计划（863 计划）（2012AA021001）；国家自然科学基金资助项目（81270554）

Protective effects of Trimetazidine on ischemia-reperfusion injury of fatty liver in rats

WANG Tengfei1，YANG Tao2△，ZHANG Wei2，FANG Zhenyu2，WANG Honghai2，LIU Lei2，ZHANG Haiming2， WANG Yuliang3   

  1. 1 First Central Clinical College of Tianjin Medical University，Tianjin 300192，China；2 Tianjin First Central Hospital；3 Key Laboratory for Critical Care Medicine of the Ministry of Health
  • Received:2015-08-03 Revised:2015-08-21 Published:2015-12-15 Online:2015-12-11
  • Contact: △Corresponding Author E-mail：yangtao5588 @medmail.com.cn E-mail:tengfeiwang6312@163.com

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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。

关键词: 曲美他嗪, 脂肪肝, 再灌注损伤, 细胞凋亡, bcl-2 相关X 蛋白质, 丙氨酸转氨酶, 天冬氨酸氨基转移酶类, 丙二醛, 超氧化物歧化酶, caspase-3

Abstract: 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.

Key words: Trimetazidine, fatty liver, reperfusion injury, apoptosis, bcl-2-associated X protein, alanine transaminase, aspartate aminotransferases, malondialdehyde, superoxide dismutase, caspase-3