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目的探讨升清胶囊治疗胆石病的可能作用机制。方法选用人L-02肝细胞分为正常组,模型组,升清胶囊高、中、低剂量组及熊去氧胆酸高、中、低剂量组。除正常组外其余各组采用LXR激动剂诱导建立胆固醇沉积模型,各给药组每孔分别加入相应2 ml含10%药物血清,正常组和模型组每孔加入2 ml含10%空白血清进行培养。24 h后观察各组肝细胞上清液及细胞总胆固醇含量及肝细胞LXR-α、FXR、ABCA1、ABCG5及ABCG8 mRNA及蛋白表达。结果模型组上清液和肝细胞总胆固醇含量,LXR-α、FXR、ABCA1、ABCG5、ABCG8 mRNA蛋白较正常组均升高(P<0.01)。升清胶囊和熊去氧胆酸各剂量组总胆固醇含量及LXR-α、FXR、ABCA1、ABCG5、ABCG8 mRNA蛋白表达有不同程度的下降,其中升清胶囊和熊去氧胆酸片在降低LXR-α及ABCA1蛋白方面呈剂量依赖性,以高剂量组效果最好(P<0.05或P<0.01);并且在下调LXR-αmRNA表达方面,升清胶囊高剂量组效果优于熊去氧胆酸高剂量组(P<0.01)。结论升清胶囊可能通过降低LXR-α、FXR及其直接靶基因ABCA1、ABCG5、ABCG8 mRNA及蛋白表达,从而改善肝细胞内胆固醇沉积,抑制结石的形成和发展。
Objective To investigate the possible mechanism of Shengqing Capsule in treating gallstone disease. Methods Human L-02 hepatocytes were divided into normal group, model group, high-dose, middle-dose and low-dose of Shengqing Capsule and high, medium and low dose of ursodeoxycholic acid. In addition to the normal group, the other groups were induced by LXR agonist to establish the model of cholesterol deposition. The corresponding 2 ml of 10% serum was added to each well in each group, and 2 ml of 10% blank serum was added to the normal group and model group to cultivate. Twenty-four hours later, the levels of hepatocyte supernatant and total cholesterol in liver cells and the mRNA and protein expressions of LXR-α, FXR, ABCA1, ABCG5 and ABCG8 were observed. Results The levels of total cholesterol, LXR-α, FXR, ABCA1, ABCG5 and ABCG8 mRNA in the supernatant and hepatocytes in the model group were significantly higher than those in the normal group (P <0.01). The content of total cholesterol and the expression of LXR-α, FXR, ABCA1, ABCG5 and ABCG8 mRNA in Sheng-qing capsule and ursodeoxycholic acid group decreased to different extents. Among them, Sheng-qing capsule and ursodeoxycholic acid tablet could reduce the content of LXR α and ABCA1 protein in a dose-dependent manner, and the effect was best at high dose (P <0.05 or P <0.01). In addition, the effect of high dose of Shengqing Capsule was better than that of ursodeoxycholic acid Acid high dose group (P <0.01). Conclusion Shengqing Capsule may reduce hepatic cholesterol deposition and inhibit the formation and development of stones by reducing the expression of ABCA1, ABCG5 and ABCG8 mRNA and protein of LXR-α, FXR and their direct target genes.