神经肽Y在孕鼠肝内胆汁淤积症胎盘中的表达及意义

The expressinon and significance of neuropeptideY(NPY) in placenta of pregnant rats with intrahepatic cholestasis

目的:观察妊娠肝内胆汁淤积症(ICP)孕鼠肝脏、胎盘结构变化;分析神经肽Y(NPY)在妊娠期肝内胆汁淤积症(ICP)孕鼠胎盘中的表达,探讨ICP的发病机制。方法:选择孕15天SD大鼠,用孕酮及乙炔雌二醇建立孕鼠ICP模型,观察孕鼠肝脏和胎盘的病理变化;应用免疫组织化学染色方法及图像分析检测ICP孕鼠(15例,实验组)及正常孕鼠(15例,对照组)胎盘中NPY的表达及定量。结果:①孕鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆酸(TBA)明显升高;肝细胞水肿,胞质内出现空泡,毛细胆管扩张、胆汁淤积;胎盘绒毛肿胀、增粗,绒毛间隙变窄,滋养细胞增生②ICP孕鼠组绒毛的NPY免疫反应呈强阳性,对照组部分滋养细胞的NPY免疫反应阳性绒毛的毛细血管内皮细胞呈弱阳性或阴性。对两组胎盘免疫组化染色进行定量分析结果显示,ICP组NPY的染色强度高于对照组,两组比较有统计学意义(P<0.05)。结论:NPY在ICP胎盘中的表达升高,提示胎盘合成和分泌血管活性物质的功能失调可能参与了ICP的发生与发展,并与ICP围生儿等不良预后有密切的关系。

Objective：To study the structure change of liver and placenta and expression of NPY in the pregnant rats with intrahepatic cholestasis,and explore the reasons for intrauterine growth retardation and intrauterine fetal death in ICP. Methods ： Rats pregnant for fifteen days were administered Estrogen and Progestrone to induce ICP. The structural changes of liver and placenta of the delivered rats were observed .And blood tests for biochemical criterion were conducted .The placentas of normal pregnancy （n=15）and ICP（n= 15） were used for studying expression and quantification of NPY by immunohistochemistry staining and image analysis . Results： ①in the experimental group ,the levels of serum total bile salt （TBA）, serum aminotransferases （ALT）,aspartate transaminase（AST） significantly increased, （P 〈0.05 ） and structural changes of hepatocytes of intrahepatic cholestasis of pregnancy （ICP） in rats included swelling ,finding bubble ,capillary expanding ,and dilation of the bile canaliculi. The placentas of ICP showed that the villi were swelling ,the size of intervilli space was smaller ,and the trophocytes were hyperplastic. ②Almost all placenta villis in vivo of ICP group showed NPY strong positive immunoreaction ,but in control group ,some trophocytes appeared NPY positive immunoreaction ,and capillary endothelium in placental villi showed NPY weak positive or negative immunoreaction ,The results of image analysis showed that the staining intensity of NPY in ICP group was significantly higher than that in the control group（ P 〈0.05 ）. Conclusion ： the placenta with ICP expressed more NPY than those of normal ,which suggests that constructive vasoactive substance （NPY） might be important to cause fetal anoxia and death.