摘要
目的探讨6位乙基取代的熊去氧胆酸(6E-UDCA)通过重组人脂肪酸结合蛋白7(FABP7)信号通路对代谢相关脂肪性肝病(MAFLD)小鼠脂质代谢的影响。方法选取野生型(WT)、WT-1小鼠、脑FABP7特异性敲除(B-FABP7^(-/-))小鼠各6只作为3组,均采用高脂肪饲料喂养16周法构建MAFLD小鼠模型,其中WT-1组、B-FABP7^(-/-)组的饲料中加6E-UDCA(23.50 mg/kg),记录各组小鼠体重和摄食情况。第16周末小鼠在麻醉下剖腹并采集腹主动脉血,检测血清TC、TG、ALT、血糖、尿酸、游离长链脂肪酸(LCFA)水平;小鼠麻醉下失血死亡后取肝脏组织,采用HE染色观察肝脏组织病理学变化,分离小鼠肝脏并称取质量,计算肝脏系数。结果WT组小鼠肝脏组织中存在明显炎性细胞浸润情况,且有大量脂肪堆积,肝细胞排列紊乱;WT-1组、B-FABP7^(-/-)组小鼠肝脏组织中炎性细胞浸润减轻,轻微脂肪堆积,且肝细胞排列紊乱明显减轻。WT-1组和B-FABP7^(-/-)组小鼠体重、摄食量、肝脏质量、肝脏系数以及TC、TG、ALT、血糖、尿酸水平均明显低于WT组(均P<0.05),游离LCFA水平高于WT组(P<0.05);B-FABP7^(-/-)组小鼠体重、摄食量、肝脏质量、肝脏系数以及TC、TG、ALT、血糖、尿酸水平均明显低于WT-1组(均P<0.05),游离LCFA水平高于WT-1组(P<0.05)。结论6E-UDCA可通过调控FABP7信号通路,进而改善MAFLD小鼠脂质代谢,提高游离LCFA水平。
Objective To investigate the regulatory effect of 6-ethyl-substituted ursodeoxycholic acid(6E-UDCA)on lipid metabolism of metabolic associated fatty liver disease(MAFLD)mice through the recombinant human fatty acid binding protein 7(FABP7)pathway.Methods Three groups of wild-type(WT),WT-1 mice,and brain FABP7 knockout(B-FABP7^(-/-))mice were used,and each group consisted of 6 mice.Each group of mice was fed high-fat food for 16 weeks to construct the MAFLD mouse model,but the food of mice in the WT-1 and B-FABP7^(-/-)groups was mixed with 6E-UDCA(23.50 mg/kg)for 16 weeks.The body weight and food intake of mice in each group were recorded.At the end of the 16th week,the mice were laparotomized under anesthesia and abdominal aorta blood was collected to detect the levels of serum TC,TG,ALT,blood glucose,uric acid and free long chain fatty acid(LCFA).After the mice died of blood loss under anesthesia,the liver tissues were taken,and the histopathological changes of the liver were observed by HE staining.The liver was separated and weighed,and the liver coefficient was calculated.Results There was significant inflammatory cell infiltration and a large amount of fat accumulation in the liver tissue of WT group mice,and the liver cell structure was disordered;the infiltration of inflammatory cells in the liver tissue of WT-1 group and B-FABP7^(-/-)group mice was reduced,with slight fat accumulation,and the structural disorder of liver cells was significantly alleviated.The body weight,food intake,liver mass,liver coefficient,TC,TG,ALT,blood glucose,and uric acid levels of mice in the WT-1 and B-FABP7^(-/-)groups were significantly lower than those of WT group(all P<0.05),while the free LCFA level was higher than that of WT group(P<0.05);the body weight,food intake,liver mass,liver coefficient,TC,TG,ALT,blood glucose,and uric acid levels of B-FABP7^(-/-)group mice were significantly lower than those of WT-1 group(all P<0.05),while the free LCFA level was higher(P<0.05).Conclusion 6E-UDCA can improve lipid metabolism and increase free LCFA levels in MAFLD mice by regulating the FABP7 signaling pathway.
作者
卢毅
赵园
龙思琴
刘清秀
潘凌云
吕娇健
LU Yi;ZHAO Yuan;LONG Siqin;LIU Qingxiu;PAN Lingyun;LYU Jiaojian(Department of Hepatology and Infectious Diseases,Lishui People's Hospital,Lishui 323000,China)
出处
《浙江医学》
CAS
2024年第21期2288-2291,共4页
Zhejiang Medical Journal
基金
浙江省医药卫生科技计划项目(2022KY1444)。
关键词
6位乙基取代的熊去氧胆酸
重组人脂肪酸结合蛋白7
代谢相关脂肪性肝病
脂质代谢
6-ethyl-substituted ursodeoxycholic acid derivatives
Recombinant human fatty acid binding protein 7
Metabolic related fatty liver disease
Lipid metabolism
作者简介
通信作者:卢毅,E-mail:18957093765@163.com。
