氯喹在小鼠肝脏热缺血-再灌注损伤中的保护作用  

Protective effects of chloroquine in a murine model of liver warm ischemia-reperfusion injury

作　　者：施敏敏[1,2] 朱沂[1] 张博森[1] 郭滟[3] 张佳年[1,2] 计骏[1,2] 蔡劬[1,2] 顾江宁[1] 陈皓[1,2] 

机构地区：[1]上海交通大学医学院附属瑞金医院外科,上海200025 [2]上海交通大学医学院附属瑞金医院上海消化外科研究所,上海200025 [3]上海交通大学医学院附属瑞金医院病理科,上海200025

出　　处：《外科理论与实践》2015年第3期206-210,共5页Journal of Surgery Concepts & Practice

基　　金：国家自然科学基金(81470894)

摘　　要：目的:研究氯喹对小鼠肝脏热缺血-再灌注损伤的保护作用,并探讨相关机制。方法:Balb/c小鼠建立肝脏部分热缺血-再灌注模型。氯喹组给予氯喹预处理,对照组给予等体积生理盐水。肝脏再灌注1、6、24 h后检测血清谷氨酸转氨酶(ALT)水平,HE染色检测肝脏病理学变化,荧光定量PCR检测炎症因子TNF-α和IL-6 m RNA水平,Western印迹检测肝脏TLR4及HMGB1表达。结果 :与对照组相比,氯喹组再灌注1、6、24 h血清ALT显著下降(P<0.05);肝细胞变性坏死、炎性细胞浸润显著减轻(P<0.01);血清TNF-α、IL-6含量显著降低(P<0.05);组织TNF-α、IL-6 m RNA表达以及HMGB1、TLR4蛋白含量显著减少(P<0.05)。结论 :氯喹预处理可显著减轻小鼠肝脏热缺血-再灌注损伤,其机制可能通过抑制HMGB1表达及TLR4信号通路。Objective To observe the protection effect of chloroquine on mice with hepatic warm ischemia-reperfusion injury and investigate the potential mechanism. Methods The models of hepatic partial warm ischemiareperfusion were built in Balb/c mice. The chloroquine group was pretreated with chloroquine and control group with normal saline. The serum ALT levels were monitored at 1, 6 and 24 h after reperfusion. HE staining was used to evaluate the pathological change of liver tissues. The m RNA expression of TNF-α and IL-6 was measured by real-time PCR and the expression of HMGB1 and TLR4 was detected by Western blot. Results In chloroquine group, the serum ALT levels were significantly decreased at 1, 6, 24 h after reperfusion（P〈0.05） compared with control group. It was shown by HE staining that pretreatment of chloroquine relieved the degeneration and necrosis of the liver tissues and infiltration of the inflammatory cells（P〈0.01）. The levels of serum TNF-α and IL-6 in chloroquine group decreased significantly（P〈0.05）compared with those in control group. The m RNA expression of TNF-α and IL-6 and the expression of hepatic HMGB1 and TLR4 also decreased significantly in chloroquine group comparing with those in control group. Conclusions Pretreatment of chloroquine could relieve hepatic warm ischemia-reperfusion injury by inhibiting both the expression of HMGB1 and TLR4 signal transduction.

关 键 词：氯喹 肝脏 热缺血-再灌注损伤 

分 类 号：R965[医药卫生—药理学]