摘要
目的探讨虎金方对高脂饮食(HFD)导致的非酒精性脂肪肝(NAFLD)模型小鼠的治疗作用及相关作用机制。方法将50只雄性SPF级C57/BL6J小鼠随机分为正常组,模型组,虎金方高、中、低剂量组。模型复制成功后,正常组和模型组小鼠按10 mL·kg^-1给予0.9%生理盐水灌胃;虎金方各组分别按高、中、低(21.24、10.62、5.31 g·kg^-1)剂量给予虎金方浓煎药液灌胃,每日1次,共4周。模型复制及给药期间每周称量小鼠体质量,并观察一般状况。给药结束后收集血液用于检测血清总胆固醇(TC)、甘油三脂(TG),并取整块肝脏,称质量并肉眼观察其外观大小、质地及颜色。一部分做成病理切片,用于HE染色,剩余肝脏组织用于以Western Blot法检测沉默信息调节因子2相关酶1(SIRT1)、过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)、活化过氧化物酶体增殖物激活受体α(PPAR-α)蛋白的表达。结果与正常组比,模型组最终体质量明显增加(P<0.001);肝脏体积增大,呈黄色,质量增加明显(P<0.001);血清TC、TG上升明显(P<0.05,P<0.001);肝小叶结构被破坏,肝细胞肿胀变形;SIRT1、PGC-1α、PPAR-α蛋白表达明显下降(P<0.05,P<0.001)。给药后,与模型组比,虎金方高剂量组最终体质量下降明显(P<0.05),肝湿质量降低(P<0.001),TG明显下降(P<0.001),SIRT1、PGC-1α、PPAR-α蛋白表达均明显增加(P<0.05,P<0.01)。结论虎金方有治疗小鼠非酒精性脂肪肝的作用,其作用机制可能与其调节SIRT1/PPAR-α通路,减轻肝脏脂质沉积有关。
Objective To investigate the therapeutic effect and related mechanism of Hu Jin Decoction on nonalcoholic fat liver disease(NAFLD)mice induced by high fat diet(HFD). Methods Fifty male SPF C57/BL6 J mice were randomly divided into 5 groups, included the normal group, the model group and three groups of Hu Jin Decoction with high,medium and low dosages. After successful replication of the models,drugs were administered to mice once a day for 4 weeks. The normal group and the model group were given 0.9% saline(10 mL·kg^-1),and the Hu Jin Decoction with high, medium and low dosage groups were given the concentrated decoction(21.24 g·kg^-1,10.62 g·kg^-1,5.31 g·kg^-1,respectively). The body mass of mice were measured weekly and the general condition was observed. After the intervention,blood specimens and intact livers were collected to determine the serum levels of AST,ALT,TC,TG. The whole livers were weighed,their appearance including the sizes,texture,and color were observed. Some of the livers were made into pathological sections for HE staining and Oil Red O staining. The expressions of SIRT1,PGC-1α and PPAR-α in the remanent tissue were detected by Western Blot. Results Compared with the normal group,the final body mass of mice increased significantly(P < 0.001),the liver volume increased with yellower color,the liver weight increased significantly(P < 0.001),the serum levels of TC,TG increased significantly(P < 0.05,P < 0.001);the structures of the hepatic lobules were destroyed,the hepatocytes were swelling and twisted,and there were lipidosis in the cells,accompanied with slight inflammatory cell infiltration. The expressions of SIRT1,PGC-1α and PPAR-α proteins were significantly decreased in the model group(P < 0.05,P < 0.001). After administration,compared with the model group,the final body mass decreased(P < 0.05),and the wet liver weight was decreased(P < 0.001);TG decreased significantly(P < 0.001),the expression levels of SIRT1,PGC-1α and PPAR-α protein increased significantly(P < 0.05,P < 0.01)in the highdose group. Conclusion Hu Jin Decoction has certain therapeutic effect on NAFLD mice,which may be related to the regulation of SIRT1/PPAR-α pathway and the reduction of the lipidosis in liver.
作者
黄明
张嘉骏
施旭光
林荣锋
武敬文
梁齐
HUANG Ming;ZHANG Jiajun;SHI Xuguang;LIN Rongfeng;WU Jingwen;LIANG Qi(School of Pharmaceutical Science,Guangzhou University of Traditional Chinese Medicine,Guangzhou 510006 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2020年第4期419-424,共6页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
广东省自然科学基金项目(2017A030313730)
深圳市福田区卫生公益性科研项目(FTWS2018056)。
作者简介
黄明,男,硕士研究生,研究方向:调理肝病方药的临床和实验研究。Email:232217883@qq.com;通信作者:施旭光,男,教授,研究方向:调理肝病方药的临床和实验研究。Email:sxg6902@126.com。
