缺血再灌注诱导小鼠肝细胞释放高迁移率族蛋白B1对P38MAPK信号通路的影响  

Effect of ischemia-reperfusion induced HMGB1 release on P38 MAPK signaling pathway in mouse liver

作　　者：李世朋[1] 何金丹[1] 于瑶[1] 王振[1] 张海明[2] 崔子林[2] 张建军[2] 朱志军[3] 

机构地区：[1]天津医科大学一中心临床学院,天津300192 [2]天津市第一中心医院东方器官移植中心、天津市器官移植重点实验室 [3]首都医科大学附属北京友谊医院普外科,北京

出　　处：《中华肝胆外科杂志》2016年第4期273-276,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：基金项目：国家高技术研究发展计划（863）项目（2012AA021001）;国家自然科学基金（81270554）;国家临床重点专科建设项目（器官移植）（201354409）;卫生公益性行业科研专项（201302009）

摘　　要：目的探讨P38MAPK通路在缺血再灌注诱导小鼠肝细胞释放高迁移率族蛋白Bl（HMGBl）中的作用及其可能机制。方法建立小鼠肝缺血再灌注损伤模型，分为假手术组（Sham）、缺血再灌注组（IR）与HMGBl释放抑制剂组（GA）。检测各组小鼠血清ALT、TNF-α和HMGBl变化，HE染色观察肝组织病理学改变，TUNEL法检测肝脏细胞凋亡情况，免疫组化与Westernblot法检测HMGBl、P-P38、P38和Caspase-3的表达。结果与Sham组相比，在IR组可见ALT（423．4±99．6）、TNF-α（84．3±21．4）和HMGB1（0．79±0．04）表达增高，而GA组则较IR组降低（P〈0．05）。病理学检查可见IR组肝细胞肿胀、肝窦变窄和灶状坏死等变化，而GA组肝组织病理改变较IR组明显改善。与Sham和GA组相比，IR组HMGB1从细胞核向核外释放增加，并且IR组的细胞凋亡率[（59．3±9．1）％]、肝组织HMGB1、p-P38和Caspase-3的表达水平最高（P〈0．05）。结论缺血再灌注诱导小鼠肝细胞释放HMGBl导致肝细胞损伤的机制可能与通过释放HMGB1而激活P38MAPK通路有关。Objective To explore the effect of HMGB1 release on P38 MAPK signaling pathway in- duced by ischemia-reperfusion （IR） in mouse liver. Methods C57BL/6 mice included sham operation group （Sham）, IR group （IR） and HMGB1 release inhibitor group （GA）. The serum AST, TNF-α and HMGB1 level of the mice were determined using a commercial assay kit. Histopatho]ogical changes were ob- served in mice livers by HE staining. HMGB1, p-P38, P38 and Caspase-3 expression were detected by im- munohistochemistry and Western blot, while cell apoptosis was detected by TUNEL assay. Results Com- pared with Sham group, serum ALT （423.4 ±99.6）, TNF-α （84. 3 ±21.4） and HMGB1 （0. 79 ±0.04） levels were increased in IR group, hut decreased in GA group （ P 〈 0.05 ）. The histological changes in the livers of the IR group included hepatocyte swelling, hepatic sinusoids narrowing and hepatocyte necrosis, which were alleviated in GA group. Compared with Sham and GA groups, there was a significant increase on HMGB1 transposition and release, and cell apoptosis [ （59.3 ± 9. 1 ） % ]in IR group （P 〈 0. 05）, but GA decreased the HMGB1 level in hepatocyte. The expression of HMGB1, p-P38 and Caspase-3 were up-regula- ted in IR group compared with those in Sham and GA groups （ P 〈 0.05 ）. Conclusion The release of HMGB1 induced by IR can cause hepatic cell damage probably by stimulating P38 MAPK signaling pathway.

关 键 词：缺血再灌注 肝细胞 蛋白激酶 P38 MAPK 高迁移率族蛋白 HMGB1 

分 类 号：R285.5[医药卫生—中药学]