大鼠肝缺血/再灌注损伤时c-fos、Bcl-2在肝组织的表达及与肝细胞凋亡的关系

目的:观察大鼠肝缺血/再灌注损伤时c-fos、Bcl-2在肝组织中的表达及与肝细胞凋亡的关系,并探讨可能的机制。方法:选健康雄性Wistar大鼠48只,随机分为对照组、缺血30min组(I组)、缺血30min即刻再灌注组(I/R组)、缺血30min再灌注1h组(I/R1h组)、缺血30min再灌注2h组(I/R2h组)、缺血30min再灌注后4h组(I/R4h组),每组8只。应用免疫组化法分别测定各组大鼠肝组织c-fos、Bcl-2的表达,应用原位细胞凋亡法测定肝细胞凋亡的情况,同时观察肝脏组织病理变化。结果:肝脏I/R可出现肝细胞明显损伤、肝细胞水肿、炎性细胞浸润,甚至有细胞坏死。与对照组比较,cfos在I组表达就有增高(P<0.01),I/R4h组达到高峰。I/R组与I组、I/R4h组与I/R2h组相比差异有统计学意义(P<0.01)。肝组织Bcl2在I组表达增高(P<0.01),I/R2～4h达到高峰。I/R4h组与I/R2h组相比差异无统计学意义(P>0.01)。细胞凋亡指数:I组、I/R组与对照组比较明显增加(P<0.01),随着时间的延长细胞凋亡指数逐渐增加。c-fos与细胞凋亡指数呈正相关(r=0.889,P<0.01),Bcl-2与细胞凋亡指数呈正相关(r=0.901,P<0.01)。结论:肝缺血/再灌注损伤可引起肝组织的损伤及肝细胞凋亡。肝细胞凋亡与cfos的表达有关。Bcl2在缺血期发挥了其抑凋亡作用,随着再灌注时间的延长,其抑凋亡作

The relation between the expression of c-fos rotein and Bcl-2 rotein in liver tissue and liver cell poptosis following liver schemia-reperfusion injury in rats

Objective: To observe the changes of c-fos protein and Bcl-2 protein in liver tissue following liver ischemia-reperfusion injury and evaluate the contribution of these two factors to liver cell apoptosis. Methods: A model of liver ischemia-reperfusion injury was established by imitation. 48 healthy rats were randomly divided into 6 groups as following (n=8): the control group (the group of sham operation), simply ischemia 30 min without reperfusion (I group), reperfusion following ischemia 30 min (I/R group), 1 hr reperfusion following ischemia 30 min (I/R1 h group), 2 hrs reperfusion following ischemia 30 min (I/R2 h group) and 4 hrs reperfusion followingishcemia 30 min (I/R4 h group). Liver tissue were observed by HE staining. The expressions of c-fos protein and Bcl-2 protein in liver tissue were examined individually by immunohistochemical technique in each group. The changes of liver cell apoptosis were measured by TUNEL labelling technique. Results: Liver ischemia/reperfusion induced remarkable hepatic cell injury. The contents of c-fos protein and Bcl-2 protein increased in I group and reached to the peak in I/R4 h group. The index of apoptosis in liver cells showed increasing during different phase of liver ischemia-reperfusion injury (P<0.01). Conclusion: The injury of liver tissue and liver cell apoptosis may be induced following the process of liver ischemia/reperfusion injury. c-fos and Bcl-2 showed increasing and may be involved into the mechanism of liver cell apoptosis. Bcl-2 may play the role in anti-liver cell apoptosis during the period of liver ischemia-reperfusion.