孟鲁司特对大鼠肠缺血再灌注继发肝损伤的保护作用研究  

Protective effects of montelukast on liver injury induced by intestinal ischemia-reperfusion in rats

作　　者：吴深宝[1] 朱旭星[1] 王向明[2] 童秀萍[1] 洪小飞[1] 金忠海[1] 

机构地区：[1]温州医科大学附属义乌中心医院消化科 [2]温州医科大学附属义乌中心医院放射科

出　　处：《中国临床药理学与治疗学》2016年第3期270-275,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省医学会临床科研基金(2012ZYC-A87);义乌市科技局科研计划资助项目(13-3-17)

摘　　要：目的:探讨孟鲁司特对Wistar大鼠肠缺血再灌注(intestinal ischemia-reperfusion,I/R)继发肝损伤的影响及机制。方法:30只大鼠随机分成3组:对照组、模型组和孟鲁司特组,复制大鼠肠缺血再灌注动物模型,孟鲁司特组术前1 h经胃灌注孟鲁司特(2 mg/kg体质量),对照组和模型组灌注同等剂量生理盐水。再灌注3 h后处死大鼠,测定各组血清丙胺酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的水平,观察各组肝脏病理改变和评分,检测大鼠肝组织半胱氨酰白三烯受体1(Cys LTR1)蛋白和mRNA表达水平,检测肝细胞凋亡水平。结果:与对照组相比,模型组ALT和AST均显著升高(P<0.01),模型组肝组织Cys LTR1蛋白和mRNA表达水平升高(P<0.05),肝组织细胞凋亡指数明显升高(P<0.05),肝脏病理损伤明显(P<0.05);与模型组相比,孟鲁司特组ALT和AST均降低(P<0.05);肝组织病理损伤减轻(P<0.05),肝细胞凋亡指数降低(P<0.05),肝组织Cys LTR1蛋白和mRNA表达水平均减低(P<0.05);肝组织Cys LTR1蛋白的表达水平与肝组织病理损伤和肝细胞凋亡指数呈正相关。结论:孟鲁司特可以明显减轻肠I/R继发肝损伤,其机制可能与抑制Cys LTR1介导的炎症反应和肝细胞凋亡有关。AIM ： To telukast on hepatic damag explore the effect of mon- e in rat with intestinal is- chemia-reperfusion （I/R） injury. METHODS ： 30 rats were divided into 3 groups （control group, mod- el group and montelukast group ）, rats in monte- lukast group were treated with montelukast before the surgery. The rat blood was extracted to detect the serum levels of ALT and AST. The liver histopatho- logic changes were also evaluated. The apoptosis in- dex of liver cells and CysLTR1 protein and mRNA expression levels were evaluated in liver tissue. RE- SULTS：Compared with control group, the levels of ALT and AST in model group were significantly in- creased （P 〈 0.01 ） , the apoptosis index of liver cells and CysLTR1 protein and mRNA expression levels were significantly elevated in liver tissue in- duced by intestinal I/R（P 〈 0.05 ） . Compared with model group, the apoptosis index of liver ceils in montelukast group was significantly decreased （P 〈 0.05 ）. Montelukast could alleviate liver tissue dam- age , including liver pathology and liver function. CysLTR1 protein and mRNA expression levels were also reduced by montelukast in rat with I/R. CysL- TR1 protein expression level of the liver tissue were positively correlated to liver tissue pathologic injury and hepatocyte apoptosis index. CONCLUSION： Montelukast can significantly reduce secondary liver injury induced by intestinal I / R, which may be re- lated to the inhibition CysLTR1- mediated inflamma- tion and apoptosis in liver cells.

关 键 词：半胱氨酰白三烯受体1 孟鲁司特 肠缺血再灌注 肝脏病理 凋亡 

分 类 号：R965.2[医药卫生—药理学]