龙胆总苷调控SREBP-1C/ACC1/FASN信号通路缓解酒精性肝病  

Total Glycosides of Longdan(龙胆) Regulate the SREBP-1C/ACC1/FASN Signaling Pathway to Alleviate Alcoholic Liver Disease

作　　者：曹后康 杨超越 张志远 李波[2] 钟明利[2] 张可锋[2] CAO Houkang;YANG Chaoyue;ZHANG Zhiyuan;LI Bo;ZHONG Mingli;ZHANG Kefeng(Guangxi Key Laboratory of Drug Discovery and Optimization,Guilin 541199;Pharmacology Laboratory of Prevention and Treatment of High Incidence of Disease,Guilin Medical University,Guilin 541199)

机构地区：[1]广西药物分子发现与成药性优化重点实验室,桂林541199 [2]桂林医学院高发病防治药理学重点实验室,桂林541199

出　　处：《中药药理与临床》2025年第1期85-89,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：广西药物分子发现与成药性优化重点实验室开放课题(编号:GKLPMDDO-2022-C07);广西高校中青年教师科研基础能力提升项目(编号:2023KY0532);国家自然科学基金(编号:82160811)。

摘　　要：目的:研究龙胆总苷对酒精性肝病(ALD)小鼠的保护作用,并基于固醇调节元件结合蛋白1c/乙酰辅酶A羧化酶1/脂肪酸合成酶(SREBP-1C/ACC1/FASN)信号通路探讨其作用机制。方法:48只小鼠随机分为正常对照组、模型对照组、水飞蓟素150 mg/kg组、龙胆总苷50、100、200 mg/kg组,每组8只。第1 w,正常对照组小鼠灌胃蒸馏水,其余各组灌胃56%可食用酒精,同时水飞蓟素150 mg/kg组和龙胆总苷各剂量组灌胃相应药物,1次/d,给药体积均为10 mL/kg;第2 w,灌胃56%可食用酒精变为2次/d,每次10 mL/kg,其余操作与第1 w相同。生化法检测小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、γ-谷氨酰基转移酶(γ-GT)、直接胆红素(DBIL)和间接胆红素(TBIL)含量,及肝组织中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)、总超氧化物歧化酶(T-SOD)、总胆固醇(TC)和总甘油三酯(TG)含量;苏木精-伊红染色和油红O染色观察肝组织病变并评分;qRT-PCR和Western blot法检测肝组织中Srebp1c、Acc1、Fasn mRNA和蛋白表达。结果:与正常对照组比较,模型对照组小鼠病理学评分、血清ALT、AST、ALP、γ-GT、DBIL、TBIL活力或含量,肝组织MDA、TC、TG含量显著升高,而T-SOD和GSH-PX活力显著降低(P<0.01),肝组织SREBP-1C、ACC1和FASN蛋白和mRNA表达显著上调(P<0.01);与模型对照组比较,水飞蓟素150 mg/kg组、龙胆总苷100、200 mg/kg组病理学评分、血清ALT、AST、ALP、γ-GT、DBIL活力或含量,肝组织TBIL、MDA、TC和TG含量明显降低,T-SOD、GSH-PX活力明显增加,肝组织SREBP-1C、ACC1、FASN蛋白和mRNA表达明显下调(P<0.05或P<0.01)。结论:龙胆总苷能够有效缓解小鼠ALD,抑制肝组织氧化应激和脂质蓄积,其作用机制可能与抑制SREBP-1C/ACC1/FASN信号通路有关。Objective:To study the effect of total glycosides of Longdan(龙胆) on alcoholic liver disease(ALD) in mice and explore the underlying mechanism based on the sterol regulatory element-binding protein-1C/acetyl coenzyme A carboxylase 1/fatty acid synthase(SREBP-1C/ACC1/FASN) signaling pathway. Methods:Forty-eight mice were randomized into normal control, model control, silymarin(150 mg/kg),total glycosides of Longdan(50,100,and 200 mg/kg) groups, with 8 mice in each group. In week 1,the normal control group received distilled water, and the other groups received 56% edible alcohol(10 mL/kg) and corresponding drugs by gavage once a day. From week 2,the mice were administrated with 56% edible alcohol at 10 mL/kg by gavage twice a day, and the remaining procedures were the same as those in week 1. Biochemical methods were used to measure the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),γ-glutamyltransferase(γ-GT),direct bilirubin(DBIL),and indirect bilirubin(TBIL) in the serum as well as the levels of malondialdehyde(MDA),glutathione peroxidase(GSH-PX),total superoxide dismutase(T-SOD),total cholesterol(TC),and total triglyceride(TG) in the liver tissue. Hematoxylin-eosin staining and oil red O staining were used for the observation and scoring of the liver lesions. Western blotting and real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR) were employed to determine the protein and mRNA levels, respectively, of SREBP-1C,ACC1,and FASN in the liver tissue. Results:Compared with the normal control group, the model control group showed increased pathological score, elevated levels of ALT,AST,ALP,γ-GT,DBIL,and TBIL in the serum and MDA,TC,and TG in the liver, decreased activities of T-SOD and GSH-PX(P<0.01),and up-regulated protein and mRNA levels of SREBP-1C,ACC1,and FASN(P<0.01). Compared with the model control group, the silymarin(150 mg/kg) and total glycosides of Longdan(100 and 200 mg/kg) groups showed decreased pathological scores, l

关 键 词：龙胆总苷 酒精性肝病 固醇调节元件结合蛋白1c/乙酰辅酶A羧化酶1/脂肪酸合成酶信号通路 脂质蓄积 

分 类 号：R28[医药卫生—中药学]