复方溶石剂对胆结石模型小鼠的作用及机制  

Effect and Mechanism of Compound Litholytic Preparation on Model Mice with Gallstone

作　　者：汤杰 陈国裕[1] 姚瑶 常云丽 季洁如[1] 胥明 TANG Jie;CHEN Guoyu;YAO Yao;CHANG Yunli;JI Jieru;XU Ming(Shanghai Pudong New Area People's Hospital,Shanghai,China 201299)

机构地区：[1]上海市浦东新区人民医院,上海201299

出　　处：《中国药业》2023年第5期57-60,共4页China Pharmaceuticals

基　　金：上海市浦东新区卫生健康委员会卫生计生科研面上项目[PW2021A-52]。

摘　　要：目的探讨复方溶石剂对胆结石模型小鼠的作用及机制。方法将100只BALB/C小鼠随机分为正常对照组(A组,等量生理盐水),模型组(B组,等量生理盐水),复方溶石剂低、中、高剂量组(C_(1)组、C_(2)组、C_(3)组,2.5,5.0,20.0 mg/kg),各20只。除A组外,其余各组小鼠均予高脂、高热量、高胆固醇饲料,以复制胆结石模型。建模成功后,A组、B组小鼠灌胃生理盐水,C_(1)组、C_(2)组、C_(3)组小鼠灌胃相应药物,连续28 d。苏木精-伊红染色,光学显微镜下观察肝脏组织病理形态;采用全自动生化分析仪测定小鼠血清肝功能指标[三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、总胆红素(TBiL)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)、总胆汁酸(TBA)、直接胆红素(DBiL)、天门冬氨酸氨基转移酶(AST)]的水平;分别采用逆转录实时荧光定量聚合酶链反应(qRT-PCR)法及免疫印迹(Western blot)法测定肝脏X受体(LXR)和羟甲基戊二酰辅酶A还原酶(HMGCR)mRNA及蛋白的表达水平。结果与B组比较,C_(1)组、C_(2)组、C_(3)组小鼠肝细胞结构逐渐恢复正常,胆管上皮细胞坏死减少;LXR mRNA和蛋白表达水平均显著升高(P<0.05),血清TG,TC,LDL-C,TBiL,DBiL,TBA,ALT,AST,ALP及肝脏HMGCR mRNA和蛋白表达水平均显著降低,且呈剂量依赖性(P<0.05)。结论复方溶石剂能减轻胆结石模型小鼠的肝脏脂肪变性,调节胆固醇及血脂,机制可能与其能下调HMGCR表达和上调LXR表达有关。Objective To investigate the effect and mechanism of compound litholytic preparation on the model mice with gallstone.Methods A total of 100 BALB/C mice were selected and randomly divided into the normal control group(group A,equal amount of normal saline),the model group(group B,equal amount of normal saline),the compound litholytic preparation low-,medium-and high-dose groups(groups C_(1),C_(2)and C_(3),2.5,5.0,20.0 mg/kg respectively),with 20 mice in each group.Except for group A,the mice in other groups were given the high-fat,high-calorie and high-cholesterol diets to replicate the gallstone models.After successful modeling,mice in the groups A and B were given the normal saline by gavage,while mice in the groups C_(1),C_(2)and C_(3)were given the corresponding drugs by gavage.All mice were administrated for continous 28 d.By the hematoxylin-eosin(HE)staining,the pathological morphology of liver tissue was observed under the light microscop.The levels of serum liver function indexes[triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),total bilirubin(TBiL),alanine aminotransferase(ALT),alkaline phosphatase(ALP),total bile acid(TBA),direct bilirubin(DBiL)and aspartate aminotransferase(AST)]in mice were measured by the full-automatic biochemical analyzer.The expression levels of liver X receptor(LXR)and hydroxymethylglutaryl-CoA reductase(HMGCR)mRNA and protein were measured by the reverse transcription real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)and Western blot,respectively.Results Compared with those in the group B,the structure of hepatocytes in the groups C_(1),C_(2)and C_(3)gradually returned to normal,and the necrosis of epithelial cells of bile duct in the groups C_(1),C_(2)and C_(3)decreased.Compared with those in the group B,the expression levels of LXR mRNA and protein in the groups C_(1),C_(2)and C_(3)were significantly higher(P<0.05),the expression levels of serum TG,TC,LDL-C,TBiL,DBiL,TBA,ALT,AST,ALP and liver HMGCR mRNA and protein in the gr

关 键 词：复方溶石剂 胆结石 肝脏X受体 羟甲基戊二酰辅酶A还原酶 作用机制 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]