胆结石豚鼠胆囊平滑肌细胞IP_3含量的变化及养肝柔肝中药的干预作用

Change of IP_3 Level in Gallbladder Smooth Muscle Cells of Guinea Pigs with Gallstones and Its Effects by Liver-Nourishing-Softening Herbs

目的通过观察实验豚鼠胆囊组织三磷酸肌醇(IP3)含量的变化,探讨养肝柔肝中药防治胆石病的作用机制。方法受试豚鼠随机分为正常组、模型组、养肝柔肝中药组(中药组)、熊去氧胆酸西药组(西药组)。除正常组外,其余3组采用高胆固醇致石食饵诱发法建立豚鼠胆结石动物模型,其中中药组、西药组分别给予相应药物干预。连续7周后,分别对实验豚鼠胆结石生成情况、胆囊组织IP3含量进行观察。结果养肝柔肝中药组能有效防止胆结石的生成,与模型组比较有显著性差异(P<0.01),其效果优于熊去氧胆酸西药组(P<0.01)。模型组动物胆囊平滑肌细胞IP3含量显著低于正常组(P<0.01);而养肝柔肝中药可明显升高胆结石豚鼠胆囊平滑肌细胞内IP3含量,与模型组比较有显著性差异(P<0.01)。结论养肝柔肝中药能显著降低胆结石的形成,其作用机制可能与上调胆囊平滑肌组织IP3的水平,激活肌醇脂质IP3/Ca2+信号转导系统,使胆囊平滑肌细胞内Ca2+释放增加进而促进胆囊的收缩有关。

Objective To explore the mechanisms of the therapeutic effects of liver-nourishing-softening herbs on gallstone. Methods The guinea pigs were randomly divided into 4 groups： normal control group, model group, herb group （Chinese herb group） and ursodeoxycholic acid-treated group（western medicine group）. The guinea pigs of the latter 3 groups were induced gallstones by high-cholesterol diet. Herbs for nourishing and softening the liver and ursodeoxycholic acid were given to the guinea pigs in the corresponding group respectively for seven weeks. The gallstone formation and the expression of IP3 in gallbladder were observed. Results Compared with the model group, herb group was able to decrease the formation rate of gallstone significantly （P〈 0.01）, which was more effective than western medicine group （P〈 0.01）. The expression of IP3 in model group was more significantly decreased as compared with that in normal control group （P〈0.01）. The expression of IP3 in herb group was more significantly increased as compared with that of model group （P 〈 0.01）. Conclusion Liver-nourishing-softening herbs may decrease the gallstone formation significantly. Its mechanism may be related to upregulating the expression of IP3 in the smooth muscles of gallbladder, activating the IP3/Ca^2＋ signal transduction systems in inositol lipid, increasing the release of the intracellular Ca^2＋ in smooth muscles and enhancing the contractibility of smooth muscles in gallbladder.