附子理中汤通过FXR-FGF15通路影响非酒精性脂肪肝胆汁酸代谢  

Fuzi Lizhong Decoction modulates bile acid metabolism in nonalcoholic fatty liver disease via the FXR-FGF15 signaling pathway

作　　者：杜念龙 杨家耀[1] 徐丹[1] 张书[1] 时昭红[1] DU Nianlong;YANG Jiayao;XU Dan;ZHANG Shu;SHI Zhaohong(Department of Gastroenterology,Wuhan First Hospital,Wuhan 430022,China)

机构地区：[1]武汉市第一医院消化内科,湖北武汉430022

出　　处：《西部医学》2024年第11期1576-1581,共6页Medical Journal of West China

基　　金：武汉市医学科研项目青年项目(中医类)(WZ21Q12)。

摘　　要：目的探讨附子理中汤对非酒精性脂肪性肝病(NAFLD)大鼠胆汁酸(TBA)代谢和肝脏损伤的影响及其机制。方法采用脂肪乳灌胃大鼠,连续4周,构建NAFLD动物模型。造模后用附子理中汤和阳性药物干预治疗,将大鼠分为对照组、模型组、附子理中汤组和阳性药物组。HE染色观察肝脏的病理变化,生化分析法检测高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(NEFA)的含量,Western blot检测回肠组织中法尼酯X受体(FXR)、成纤维细胞生长因子15(FGF15)的蛋白表达和肝脏组织中FXR的蛋白表达,RT-PCR检测回肠组织中FXR、FGF15的mRNA表达和肝脏组织中FXR的mRNA表达,ELISA检测肝组织TBA水平。结果与对照组比较,模型组大鼠肝脏出现严重病理损伤,血清中HDL-C含量下降,LDL-C和NEFA含量增加(均P<0.01),大鼠肝脏组织中FXR蛋白、mRNA表达和回肠组织中FXR、FGF15的蛋白、mRNA表达上升(均P<0.01),肝组织中TBA水平下降(P<0.01)。与模型组比较,附子理中汤组和阳性药物组大鼠肝脏病理损伤缓解,HDL-C含量增加,LDL-C和NEFA含量下降(均P<0.05),大鼠肝组织中FXR蛋白、mRNA表达和回肠组织中FXR、FGF15蛋白、mRNA表达下降(P<0.05),肝组织中TBA水平增加(P<0.01)。结论附子理中汤治疗可通过激活回肠FXR-FGF15信号,增加肝脏TBA代谢,缓解NAFLD引起的肝损伤。Objective To investigate the effects of Fuzi Lizhong Decoction on bile acid(TBA)metabolism and liver injury by FXR/FGF15 axis.Methods The non-alcoholic fatty liver disease(NAFLD)rat model was established by intragastric administration of fat milk for four weeks.After modeling,the rats were treated with Fuzi Lizhong decoction and positive drug.On the basis of that,the rats were divided into control group,model group,Fuzi Lizhong decoction group and positive drug group.The pathological changes of liver were observed by HE staining.The contents of high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and free fatty acid(NEFA)were detected by biochemical analysis.The protein expression of farnesol receptor X(FXR),and fibroblast growth factor 15(FGF15)in ileum,and FXR in liver were detected by western blot.The mRNA expression of FXR,and FGF15 in ileum,and FXR in liver were detected by RT-PCR.The level of TBA in liver tissue was detected by ELISA.Results Compared with control group,the liver of rats in model group showed serious pathological injury,the contents of HDL-C decreased,LDL-C and NEFA increased(P<0.05).The protein expressions of FXR in the liver and FXR and FGF15 in the ileum increased(P<0.01).The level of TBA decreased(P<0.01).Compared with model group,liver pathological injury was relieved in Fuzi Lizhong decoction group and positive drug group,the contents of HDL-C were increased,LDL-C and NEFA were decreased(P<0.05).The protein expressions of FXR and FGF15 were decreased(P<0.05),and the level of TBA was increased(P<0.01).Conclusion Fuzi Lizhong Decoction can increase liver TBA metabolism by activating FXR-FGF15 signal in ileum,thus alleviating liver injury caused by nonalcoholic fatty liver.

关 键 词：附子理中汤 非酒精性脂肪肝 法内甾体受体X 成纤维细胞生长因子15 胆汁酸 

分 类 号：R575.5[医药卫生—消化系统]