目的 观察大柴胡颗粒对胆色素结石豚鼠胆囊黏膜表皮生长因子（EGF）表达水平，肝、胆超微结构，肝组织胆固醇7α-羟化酶（CYP7A1）mRNA水平以及胆盐转运子BSEP、MRP2表达水平的影响，明确其对胆色素结石豚鼠的保护作用机制。方法 采用饲料法复制胆色素结石豚鼠模型，免疫组化法观察大柴胡颗粒（1.1、2.2、4.4 g/kg）对胆色素结石豚鼠的胆囊EGF水平的影响，透射电镜观察肝胆组织超微结构的改变，RT-PCR法检测肝组织CYP7A1 基因表达水平，Western blotting法检测肝脏中BSEP、MRP2表达水平，以熊去氧胆酸作为阳性对照。结果 大柴胡颗粒对胆结石豚鼠胆囊黏膜EGF表达影响不明显，但较好地改善其肝胆超微结构，其2.2、4.4 g/kg剂量组还能增加肝脏组织CYP7A1的基因转录（P＜0.05、0.01）和BSEP、MRP2蛋白表达水平（P＜0.05）。结论 大柴胡颗粒抑制豚鼠胆色素结石形成可能与其影响豚鼠胆汁酸代谢、促进胆盐转运子功能、保护肝胆细胞器结构有关，而与胆囊黏膜EGF功能无明显关系。

Objective To study the effect of Dachaihu Granules (DG) on the expression of epidermal growth factors (EGF) of gallbladder mucosa in guinea pigs with bile pigment stones (BPS), the ultrastructure of liver and gallbladder epithelial cells, the level of cholesterol 7 alpha-hydrolase (CYP7A1) mRNA, and the expression of bile salt transporters, BSEP and MRP2, in liver cells for explaining the protective mechanism of the drug further. Methods The guinea pigs with BPS were established by fodder method. With the interference of DG (1.1, 2.2, and 4.4 g/kg), the expression of EGF locating on the bile gallbladder was detected by immunohistochemistry. The ultrastructure of liver and gallbladder epithelial cells was detected by transmission electron microscopy (TEM). The CYP7A1 mRNA expression level in liver was detected by RT-PCR and the expression levels of BSEP and MRP2 in liver were detected by Western blotting with the ursodeoxyholic acid as positive control. Results There was no obvious change on the expression of EGF in the bile gallbladder with the administration of DG. However, the ultrastructure of liver and gallbladder epithelial cells was improved obviously. In addition, in 2.2 and 4.4 g/kg DG groups the transcription of CYP7A1 mRNA (P < 0.05, 0.01) and expression of BSEP and MRP2 (P < 0.05) in liver cells were increased. Conclusion The mechanism of DG inhibiting the formation of BPS is related to influencing the bile acid metabolism, improving the bile salt transporter function, and protecting the organelles of liver and gallbladder epithelial cells. While EGF in bile gallbladder might not be involved in the mechanism.

江苏省科技成果转化专项课题（BA2010094）