升清胶囊对胆固醇结石小鼠核受体及三磷酸腺苷结合盒(ABC)转运蛋白影响的研究  

Research on effect of Shengqing Capsule on nuclear receptors and ATP binding cassette transporters in cholesterol gallstone mice

作　　者：沈亮[1] 胡诚 章学林[1] 顾宏刚[1] 张静喆[1] 梁晓强[1] SHEN Liang;HU Cheng;ZHANG Xuelin;GU Honggang;ZHANG Jingzhe;LIANG Xiaoqiang(Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Center of Science and Techndogy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200032 [2]上海中医药大学科技实验中心,上海201203

出　　处：《上海中医药杂志》2021年第8期88-93,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家中医药管理局全国中医学术流派传承工作室第二轮建设项目(国中医药人教函[2019]62号);上海市卫健委资助项目(2018JP012);上海市卫健委进一步加快中医药事业发展三年行动计划项目(ZY[2018-2020]-CCCX-1007)。

摘　　要：目的探讨升清胶囊对胆固醇结石模型小鼠核受体及三磷酸腺苷结合盒(ABC)转运蛋白表达的影响。方法将30只C57BL/6J小鼠随机分为正常组、模型组和升清胶囊组,每组10只;模型组和升清胶囊组采用喂养高脂致石饲料连续7周诱导胆固醇结石模型,正常组喂养正常饲料;升清胶囊组在造模的同时给予相应药物灌胃,正常组和模型组给予等量0.9%NaCl溶液灌胃。各组均于造模结束后取材,观察成石率,HE染色观察胆囊和肝脏大体形态变化,酶比色法检测血清及肝脏TG、TC、TBA含量,Real-time PCR和Western blot法分别检测肝脏LXR-α、FXR、ABCA1、ABCG5、ABCG8 mRNA及蛋白表达。结果(1)与正常组比较,模型组成石率升高(P<0.05),胆囊和肝脏大体形态学存在不同程度损伤;与模型组比较,升清胶囊组成石率降低(P<0.05),胆囊和肝脏大体形态学均有不同程度改善。(2)与正常组比较,模型组血清和肝脏TC、TG含量升高,肝脏TBA含量降低,肝脏LXR-α、FXR、ABCA1、ABCG5、ABCG8 mRNA及蛋白表达均升高(P<0.05,P<0.01);与模型组比较,升清胶囊组血清和肝脏TC、TG含量降低,LXR-α、FXR、ABCG5、ABCG8 mRNA及蛋白表达均降低,ABCA1蛋白表达降低(P<0.05,P<0.01)。结论升清胶囊可能是通过下调LXR/FXR及其直接靶基因ABC转运蛋白来降低C57小鼠结石成石率。Objective To study effect of Shengqing Capsule on nuclear receptors and ATP Binding Cassette(ABC)Transporters in cholesterol gallstone mice.Methods 30 C57 BL/6 J mice were randomly divided into normal group,model group and Shengqing Capsule group,with 10 mice in each group.The cholesterol gallstone model group was developed by feeding high-fat lithogenic diet for 7 consecutive weeks,while the normal group was fed with normal diet.The Shengqing Capsule group was administered drug(0.355 g/kg·d)by gavage when modeling,while the normal group and model group were administered the same amount of normal saline by gavage.After modeling,the stone formation rate in each group was observed.The gross morphological changes of gallbladder and liver were assessed by the H&E staining,the levels of Triglycerides(TG),total cholesterol(TC),and total bile acids(TBA)in serum and liver were measured by GPO-PAP.Real time-PCR and western blot were performed to detect the mRNA and protein expression levels of LXR-α,FXR,ABCA1,ABCG5,ABCG8 in the liver respectively.Results(1)Compared with the normal group,the stone formation rate increased(P<0.05),and the gross morphology of gallbladder and liver was damaged in various degrees in the model group.The stone formation rate reduced(P<0.05),the gross morphology of gallbladder and liver was improved in various degrees of the Shengqing Capsule group compared with those of the model group.(2)Compared with the normal group,the levels of TC and TG in serum and liver increased,but the level of TBA in liver decreased,the mRNA and protein expressions of LXR-α,FXR,ABCA1,ABCG5,ABCG8 in liver increased in the model group(P<0.05,P<0.01).Compared with the model group,the leuel of TC and TG in serum and liver significantly decreased,the mRNA of LXR-α,FXR,ABCG5 and ABCGB decreasecl,and the protein expression of ABCA1 decreased in the Shenqing Capsule group(P<0.05,P<0.01)Conclusion Shengqing Capsule may down-regulate LXR-α/FXR and its direct gene ATP-binding cassette transports to reduce the stone formatio

关 键 词：升清胶囊 胆固醇结石 小鼠 核受体LXR-α/FXR ABC转运蛋白 

分 类 号：R285.5[医药卫生—中药学]