前列腺素E1对阻塞性黄疸大鼠肝细胞凋亡及凋亡相关蛋白表达的影响

Effects of Prostaglandin E_1 on hepatic apoptosis and the expression of apoptosis-related proteins in rats with obstructive jaundice

目的探讨前列腺素E1(prostaglandin E1,PGE1)对阻塞性黄疸大鼠肝细胞凋亡的影响及其可能机制。方法选择雄性健康Wistar大鼠72只,建立阻塞性黄疸大鼠模型,随机分为三组:假手术组(SH组)、胆总管结扎组(OJ组)、胆总管结扎+前列腺素E1给药组(PGE1组),分别于手术后3、7、10 d各组测定胆红素(TBil,DBil)和转氨酶(ALT,AST),同时取肝组织在显微镜下观察病理变化。肝细胞凋亡采用TUNEL法检测,并计算凋亡指数(AI)。采用免疫组化法检测NF-κB和iNOS蛋白在各组肝脏中的表达。结果与OJ组比较,PGE1组大鼠血清转氨酶和胆红素水平下降(P<0.05)。TUNEL结果显示,与OJ组相比,PGE1组细胞凋亡有所减轻(P<0.01)。免疫组化结果显示,与OJ组相比,PGE1组的大鼠肝细胞iNOS蛋白表达降低,NF-κB表达升高,差异均有显著性(P<0.05)。结论前列腺素E1可以减轻阻塞性黄疸大鼠的肝细胞凋亡,其机制可能通过直接或间接下调促凋亡蛋白iNOS、上调抗凋亡蛋白NF-κB的表达有关。

Objective To investigate the effect of Prostaglandin E1 on hepatic apoptosis in rats with obstructive jaundice （OJ） and its possible mechanisms. Methods Seventy-two health SD rats were divided into three groups randomly：sham operation group （SH group）, the OJ group （ OJ group） and the group of OJ rats administered Prostaglandin E1 （PGElgroup）. The OJ and PGE1 group were established by double-ligating bile duct. Tail vein injection of Prostaglandin E1 was only administered daily in PGE1 group. Three groups of rats were sacrificed on the 3,7 and 10 days of postoperation respectively. The levels of serum total bilirubin （TBil）, direct bilirubin （ DBil）, ala- nine aminotransferase（ALT） and aspartate aminotransferase（AST） were tested and the tissue＇ s histopathology changes were observed. Apoptosis of hepatocytes was tested by TUNEL and accounted apoptosis index（AI） ,the immunohistochemical technique was used for de- tecting the NF-KB and iNOS protein expression. Results In PGE1 group, the values of serum ALT, AST,TBil and DBil were lower than those in OJ group（ P 〈 0. 05 ）. Meanwhile, Prostaglandin El degraded the expression of iNOS in hepatic tissues, and enhanced the expres- sion of NF-KB（ P 〈 0. 05 ）. In addition, the quantity of positive TUNEL cells in PGE1 group was lower than that in OJ group（ P 〈 0. 01 ）. Conclusion PGE1 can decrease hepatic apoptosis in rats with obstructive jaundice （OJ）, to which the modulation of NF-κB and iNOS may contribute.