PPARγ激动剂15d-PGJ_2在大鼠肝脏缺血-再灌注损伤中的保护作用及机理

Protective Effect of Peroxisome Proliferator-Activated Receptor γ Activator 15-Deoxyprostaglandin J_2 in Rat Hepatic Ischemia-Reperfusion Injury and Its Mechanism

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂15-脱氧前列腺素J2(15d-PGJ2)在大鼠肝脏缺血-再灌注损伤中的保护作用及机理。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、缺血-再灌注损伤组(缺血-再灌注组)、15d-PGJ2预处理组(15d-PGJ2组)及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,取肝脏组织检测髓过氧化物酶(MPO)活性、NF-κB活性、TNF-α含量和ICAM-1表达。结果与假手术组相比,其余3组血清ALT和AST水平、肝脏组织MPO和NF-κB活性、TNF-α含量和ICAM-1表达均增加(P<0.05)。与缺血-再灌注组相比,15d-PGJ2组血清ALT和AST水平、肝脏组织MPO和NFκ-B活性、TNF-α含量和ICAM-1表达均明显降低(P<0.05);而15d-PGJ2+GW9662组与缺血-再灌注组相比有差异但无统计学意义(P>0.05)。与15d-PGJ2组相比,15d-PGJ2+GW9662组血清ALT和AST水平、肝脏组织MPO和NF-κB活性、TNF-α含量和ICAM-1表达明显增加(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,其机理可能是通过PPARγ途径抑制NFκ-B活性,减少TNF-α和ICAM-1炎症介质的释放实现的。

Objective To investigate the protective effect of peroxisome proliferator-activated receptor γ （PPARγ） activator 15-deoxyprostaglandin J2 （15d-PGJ2） in rat hepatic ischemia-reperfusion injury and its mechanism. Methods The models of 70% warm ischemia-reperfusion injury were established in SD rats, rats were randomly divided into 4 groups： sham operation group, ischemia-reperfusion group, 15d-PGJ2 group and 15d-PGJ2 ＋ GW9662 group. After reperfusion, serum AST and ALT levels were determined; the liver tissues were removed for measurement of activity of NF-κB and myeloperoxidase （MPO）, TNF-α content and expression of ICAM-1. Results Compared with sham operation group, the serum levels of ALT and AST, and the activities of MPO and NF-κB, TNF-α content and expression of ICAM-1 in ischemia-reperfusion group, 15d-PGJ2 group and 15d-PGJ2 ＋GW9662 group were greatly improved （P〈0.05）. Compared with ischemia-reperfusion group, the serum levels of ALT and AST and the activities of MPO and NF-κB, TNF-a content and expression of ICAM-1 in 15d-PGJ2 group were sig- nificantly decreased （P〈0.05）. Compared with 15d-PGJ2 group, the serum levels of ALT and AST, and the activities of MPO and NF-κB, TNF-α content and the expression of ICAM-1 in 15d-PGJ2 ＋GW9662 group were obviously increased （P〈0.05）. Conclusion PPAR7 activator 15d-PGJ2 could protect against ischemia-reperfusion injury in rats, with its possible mechanism of inhibiting NF-κB activation and down-regulating TNF-α content and ICAM-1 expression in a PPARγ dependent fashion.