过氧化物酶体增殖物激活受体γ激动剂15-脱氧前列腺素J2对小移植肝再灌注损伤的保护作用  

Protective effect of peroxisome proliferator-activated receptor γ agonist 15d-PGJ2 against reperfusion injury in small-for-size rat liver grafts

作　　者：宋军[1] 徐为[1] 丁志龙[1] 李文美[1] 李向农[1] 王学浩[2] 

机构地区：[1]徐州医学院附属医院普外科,江苏221002 [2]南京医科大学第一附属医院肝脏移植中心

出　　处：《中华实验外科杂志》2011年第8期1318-1320,共3页Chinese Journal of Experimental Surgery

基　　金：基金项目：江苏省医学重点学科--江苏省人民医院肝病外科临床医学中心（ZX200605）开放基金资助项目（KF200917）;徐州医学院院长基金资助项目（2010KJZ22）;徐州医学院院长基金资助项目（09KJZ10）

摘　　要：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）对小移植肝大鼠再灌注损伤的保护作用及其机制。方法将108只SD大鼠随机分为3组：（1）15d—PGJ2预处理组；（2）15d—PGJ2＋GW9662组；（3）生理盐水对照组（NS组）。检测术后6、24、72h血清丙氨酸转氨酶（ALT）和天门冬氨酸氨基转移酶（AST）水平；检测术后24h肝组织中丙二醛（MDA）和超氧化物歧化酶（SOD）含量；检测肝组织中髓性过氧化物酶（MPO）活性以反映中性粒细胞的浸润；酶联免疫吸附试验（ELISA）检测肝组织中肿瘤坏死因子（TNF）-α水平；观察术后24h光镜下肝组织病理学变化。结果与NS组和15d—PGJ2＋GW9662组比较，15d—PGJ2预处理组术后6、24、72h血清ALT和AST水平明显降低（P〈0．01）；术后24hSOD活性明显升高而MDA含量降低，差异有统计学意义（P〈0．01）；肝组织中TNF-α含量及MPO活性亦明显降低，差异有统计学意义（P〈0．01）；苏木素-伊红（HE）染色显示：NS组和15d—PGJ2＋GW9662组术后24h，表现为明显的肝细胞空泡变性，肝窦扩张，炎症细胞浸润；15d—PGJ2组较其他两组肝组织损伤轻微。结论PPARγ激动剂15d—PGJ2对小移植肝术后再灌注损伤有明显的保护作用，其保护机制可能与提高机体抗氧化能力，抑制脂质过氧化及减轻炎症反应密切相关。Objective To investigate the protective effect of peroxisome proliferator-activated receptor 7 （PPARγ） agonist 15d-PGJ2 against reperfusion injury in small-for-size liver grafts and its probable mechanisms. Methods 108 adult male SD rats were randomly divided into three groups： （ 1 ） 15d- PGJ2 group; （2） 15d-PGJ2 ＋ GW9662 group; （3） NS control group. Serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT） levels at 6, 24 and 72 h after repeffusion and histopathological changes were analyzed, the contents of malondialdehyde （MDA） and superoxide dismutase （SOD） in liver grafts after 24 h were determined, myeloperoxidase （MPO） activity was examined to assay neutrophil infiltration into the grafts at 24 h after reperfusion, and transforming growth factor （TGF）-α levels at 24 h after reperfusion were measured by using enzyme-linked immunosorbent assay （ELISA method）. Results As compared with NS control group and 15d-PGJ2 ＋ GW9662 group, serum AST and ALT levels were significantly reduced at 6, 24 and 72 h after reperfusion in 15d-PGJ2 group （P 〈 0. 01 ）. Histopathological analysis revealed apparent bulb-like degeneration, hepatic sinusoid dilation, and inflammatory cell infiltra- tion in periportal area at 24 h in NS group and 15d-PGJ2 ＋ GW9662 group after transplantation, while in the 15d-PGJ2 group, minimal damage was observed at 24 h after transplantation under the light microscopy, the contents of MDA were lower and SOD levels were higher than in other groups （ P 〈 0. 01 ）. As compared with NS group and 15d-PGJ2 ＋ GW9662 group, TNF-α levels and MPO activity at 24 h after transplantation were also significantly decreased in 15d-PGJ2 group （ P 〈 0. 01 ）. Conclusion PPAR＇y agonist 15d-PGJ2 could ameliorate reperfusion injury in small-for-size liver grafts significantly, which was mediated in part by increasing antioxidant ability, inhibiting lipid peroxidation, and down-regulating inflammatory reaction.

关 键 词：过氧化物酶体增殖物激活受体Γ 肝移植 再灌注损伤 

分 类 号：R285.5[医药卫生—中药学]