目的：观察加味茵陈蒿汤对雌激素致肝内胆汁淤积症大鼠肝脏水通道蛋白8（AQP8）mRNA和蛋白表达的影响，探讨加味茵陈蒿汤治疗妊娠肝内胆汁淤积症可能的分子机制。方法：50只SD雌性大鼠，体质量180-200 g，随机分为正常组（N，n=10）和模型组（M’，n=40）。M’组大鼠皮下注射17-α乙炔雌二醇5 mg·kg^-1·d^-1，连续5天，建立肝内胆汁淤积症模型，N组大鼠给予相同体积的丙二醇皮下注射。5天后，M’组大鼠随机分为模型组（M，n=10）、加味茵陈蒿汤高剂量（Zg，n=10）、中剂量（Zz，n=10）和低剂量组（Zd，n=10），分别给予生理盐水和高、中、低剂量的加味茵陈蒿汤灌胃，连续7天。7天后处死大鼠，留取肝脏组织，置于液氮中保存，分别运用实时定量PCR法及蛋白免疫印迹法检测AQP8 mRNA与蛋白表达情况。结果：与正常组（N）比较，模型组（M）大鼠肝脏组织AQP8 mRNA与蛋白表达水平降低（P<0.01）。与模型组（M）比较，高、中和低剂量的加味茵陈蒿汤均可增加大鼠肝脏组织AQP8 mRNA与蛋白表达水平（P<0.05）。此外，研究还发现，随着加味茵陈蒿汤给药剂量的增加，其上调AQP8 mRNA和蛋白表达的作用增强。结论：加味茵陈蒿汤治疗妊娠肝内胆汁淤积症的分子机制可能是通过增加肝脏组织AQP8 mRNA与蛋白表达水平实现的。

This study was aimed to investigate the effect of modified Yin-Chen-Hao (YCH) decoction on the expression of aquaporin-8 (AQP8) mRNA and protein in rats with estrogen-induced cholestasis, in order to explore the potential mechanism of YCH decoction in the treatment of intrahepatic cholestasis during pregnancy. A total of 50 SD female rats, which were weighed between 180 g to 200 g, were randomly divided into the normal group (N, n = 10) and the model group (M’, n = 40). The animal model of intrahepatic cholestasis was induced by subcutaneous injection of 17-α-ethinylestradiol (5 mg·kg^-1·d^-1) for 5 days of rats in M’ group. The same volume of propylene glycol was subcutaneously injected to rats in N group. Five days later, rats in M’ group were divided into the model group (M, n = 10), high-dose (Zg, n = 10), middle-dose (Zz, n = 10) and low-dose (Zd, n = 10) modified YCH decoction group. The intragastric administration of normal saline, high-dose, middle-dose and low-dose modified YCH decoction were given to each group for 7 days, respectively. Then, rats were sacrificed and the liver tissues were removed and stored in liquid nitrogen. The expression of AQP8 mRNA and protein were detected by real-time polymerase chain reaction (RT-PCR) and western blotting analysis. The results showed that compared with the normal group (N), the expression of AQP8 mRNA and protein in liver tissues of rats in the model group (M) were decreased (P < 0.01). Compared with the model group (M), the high-dose, middle-dose and low-dose modified YCH decoction can increase the expression of AQP8 mRNA and protein in liver tissues (P < 0.05). Moreover, along with the dose increasing of modified YCH decoction, the upregulation of AQP8 mRNA and protein was increased. It was concluded that the molecular mechanism of modified YCH decoction in treatment of intrahepatic cholestasis during pregnancy may be through the increasing of AQP8 mRNA and protein in liver tissues.

国家自然科学基金委青年基金项目（81102611）：补肾祛湿法对雌孕激素共诱导肝内胆汁淤积症胆汁酸排泌通路的调控，负责人：侯莉莉。