阻塞性黄疸大鼠法尼酯衍生物X受体表达及加味大柴胡汤作用的研究

Effects of Modified Major Decoction of Bumleurum Earnesoid X Receptor in Rat with Obstructive Jaundice

目的研究法尼酯衍生物X受体(FXR)对胆汁酸代谢的作用,以及加味大柴胡汤对FXR的表达的影响。方法制作急性阻塞性黄疸大鼠模型,分为7、14、21d3个时段,每个时段又分为胆总管结扎+加味大柴胡汤组、胆总管结扎+TUD-CA、胆总管结扎组+生理盐水组、假手术+生理盐水组等4组,每组6只。生化检测ALT、TB、TBA、ALP;免疫组化法检测FXR蛋白表达。结果胆道梗阻后,随梗阻时间的延长,FXR表达减弱。血清TBA、ALT、ALP、TB含量明显增加。加味大柴胡汤使FXR表达上调,血清TBA、ALT、ALP、TB明显下降,肝脏病变减轻。结论阻塞性黄疸时FXR表达可调节胆汁酸代谢。加味大柴胡汤可以上调FXR蛋白表达,促进胆汁酸代谢,从而减轻肝脏损害。

Objective To observe the effect of famesoid X receptor（FXR） on bile acid metabolism and the influence of modified major decoction of Bupleurum（MMDP） on the FXR expression in rats with obstructive jaundice Methods Acute obstructive jaundice models in SD rats, which were randomly divided into three time points, namely 7, 14, 21 day, were established. In each time point, there were four groups, 6 rats each： BDL ＋ MMDB, BDL ＋ TUDCA, BDL ＋ NS and SO ＋ NS. The concentrations of serum total bile acids（TBA）, total bilirubin（TB）, alanine aminotrasferase（ALT）, alkaline phophatase（ALP） were measured with biochemistry and micropathologic features of rat liver tissues respectively observed with microscopy. The level of FXR protein in the liver was tested with immunohistochemistry. Results Serum ALT, ALP, TB, TBA levels after bile duct obstruction significantly increased and the trend was gradually getting worse with time, while the expression of FXR protein decreased. The expression of FXR in DBL ＋ herb group increased. Serum ALT, ALP, TB, TBA levels in the BDL ＋ herb group significantly decreased and liver injury reduced. Conclusion The expression level of FXR protein may regulate bile acid metabolism; MMDB can mediate the expression level of FXR protein, promote bile acid metabolism and reduce the liver injury.