PPARγ激动剂15d-PGJ_2对大鼠肝缺血再灌注损伤中细胞凋亡的影响  

Effect of peroxisome proliferator-activated receptor γ activator 15d-PGJ2 in rat hepatic ischemia-reperfusion injury

作　　者：曹晓飞[1] 张峰[1] 张业伟[1] 

机构地区：[1]南京医科大学第一附属医院肝脏外科,江苏南京210029

出　　处：《中国现代医学杂志》2008年第18期2632-2634,2638,共4页China Journal of Modern Medicine

基　　金：国家自然科学基金青年科学基金资助(No:30600576);江苏省医学领军人才基金资助

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂15d-PGJ2对大鼠肝脏缺血再灌注损伤中细胞凋亡的作用及可能的机制。方法建立70%的大鼠肝脏缺血再灌注损伤模型,40只SD大鼠随机均分为4组:假手术组(SO组)、缺血再灌注损伤组(IR组)、15-脱氧前列腺素J2预处理组(15d-PGJ2组),15d-PGJ2+GW9662预处理组(15d-PGJ2+GW9662组)。再灌注后,取静脉血检测肝血清酶(ALT、AST)水平,取肝脏组织TUNEL法检测缺血肝脏细胞凋亡指数(apoptotic index,AI),免疫组化检测Bcl-2、Bax、Caspase-3表达。结果与SO组相比,其他3组血清ALT和AST水平、肝脏细胞AI、Bax、Bcl-2及Caspase-3均升高(P<0.05)。与IR组相比,15d-PGJ2组血清ALT和AST水平、肝脏细胞AI、Bax及Caspase-3表达降低,Bcl-2表达升高(P<0.05);而15d-PGJ2+GW9662组与缺血再灌注组相比差异无显著性(P>0.05)。与15d-PGJ2组相比,15d-PGJ2+GW9662组血清ALT和AST水平、肝脏细胞AI、Bax及Caspase-3表达增加,Bcl-2表达减少(P<0.05)。结论PPARγ激动剂15d-PGJ2对肝脏缺血再灌注损伤有保护作用,其机制可能是通过PPARγ激活上调Bcl-2、下调Bax的表达和抑制Caspase-3活性实现的。[Objective] To investigate the effect of peroxisome proliferator-aetivated receptor γ（PPAR3,） activator 15-deoxyprostaglandin J2 （15d-PGJ2） in rat hepatic ischemia- repeffusion injury and its mechanism. [Methods] The model of 70% warm ischemia- reperfusion injury was established in SD rats, rats were divided at random into 4 groups ： sham operation group （SO group）, ischemia-reperfusion group（IR group）, 15-deoxyprostaglandin J2 treatment group （15d-PGJ2 group）, 15-deoxyprostaglandin J2 plus 2-chloro-5-nitrobenzanilide treatment group （15d- PGJ2 plus GW9662 group）. After reperfusion, AST and ALT levels in serum were determined, the liver tissue was removed for measurement of the apoptotic index by TUNEL assay and the expression of Bax,Bcl-2 and caspase-3 proteins in ischemic hepatocytes by immunohistochemistry. [Results] Compared with SO group, the serum levels of ALT and AST and the apoptotic index of hepatocytes and Bax,Bcl-2 and Caspase-3 proteins in IR group and 15d- PGJ2 group and 15d-PGJ2 plus GW9662 group was greatly increased （P 〈0.05）. Compared with IR group, the serum levels of ALT and AST and the apoptosis index of hepatocytes and Bax and Caspase-3 in 15d-PGJ2 group decreased, with Bcl-2 increased （P 〈0.05）. Compared with 15d-PGJ2 group, the serum levels of ALT and AST and the apoptosis index of hepatocytes and Bax and Caspase-3 in 15d-PGJ2 plus GW9662 group increased, with Bcl-2 decreased （P 〈0.05）. [Conclusions] PPARγ activator 15d-PGJ2 could protect against ischemia -reperfusion injury in rats ,with its possible mechanism of upregulating the expression of Bcl-2, inhibiting the expression of Bax and Caspase-3 and prohibiting hepatocyte apoptosis in a PPARγ dependent fashion.

关 键 词：过氧化物酶体增殖物激活受体Γ 15-脱氧前列腺素J2 再灌注损伤 凋亡 

分 类 号：R657.3[医药卫生—外科学] R-332[医药卫生—临床医学]