摘要
目的研究桑芪益气养阴方对胰岛素抵抗大鼠肝脏组织乙酰辅酶A羧化酶1(Acetyl-coa carboxylase 1,ACC1)/脂肪酸合成酶(fatty acid synthase,FASN)/硬脂酰-辅酶A去饱和酶1(stearoyl-CoA desaturase 1,SCD1)通路及葡萄糖转运蛋白2(glucose transporter2,GLUT2)的影响。方法雄性SD大鼠48只,根据基础血糖水平分为空白组、模型组、阳性药组、桑芪益气养阴方低、中、高剂量组。采用甲状腺素皮下注射、连续高脂饲料喂养合并链脲佐菌素注射复合因素造模。空白组大鼠不予给药,模型组大鼠给予给予0.9%氯化钠溶液,阳性药组十味消渴胶囊灌胃剂量为1.32 g/kg、桑芪益气养阴方低、中、高剂量组灌胃剂量分别为1.25、2.5、7.5 g/kg。连续给药30天,比色法检测大鼠外周血谷丙转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)和肝脏肝糖原、游离脂肪酸(free fat acid,FFA)、丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)含量,使用RT-PCR及Western blot分别检测大鼠ACC1、FASN、SCD1、GLUT2的mRNA和蛋白表达。结果与空白组相比,模型组大鼠ALT、AST、MDA显著升高,SOD、肝糖原、GSH-PX显著降低(P<0.05,P<0.01),ACC1、FASN、SCD1的mRNA和蛋白表达水平显著升高,GLUT2的mRNA和蛋白表达水平显著降低(P<0.01);与模型组比较,各干预组大鼠ALT、AST、MDA显著降低,SOD、肝糖原、GSH-PX显著升高(P<0.05,P<0.01),桑芪益气养阴方中、高剂量组FFA含量显著降低(P<0.05,P<0.01),桑芪益气养阴方中、高剂量组ACC1、FASN、SCD1的mRNA和蛋白表达水平显著降低(P<0.01),GLUT2的mRNA和蛋白表达水平显著升高(P<0.01)。结论桑芪益气养阴方可调节大鼠肝脏糖脂代谢紊乱,缓解氧化应激,预防肝损伤,其机制可能与抑制ACC1/FASN/SCD1和上调GLUT2基因和蛋白表达相关。
Objective To study the effects of Sangqi Yiqi Yangyin Fomula on ACC1/FASN/SCD1 pathway and GLUT2 in insulin resistant rats.Methods According to the basal blood glucose level,a total of 48 male Sprague Dawley rats were divided into blank group,model group,positive drug group(Shiwei Xiaoke Capsule),and low,medium and high dose groups of Astragalus mulberry leaf and Yuzhu granules.Subcutaneous injection of thyroxine combined with intraperitoneal injection of STZ was used to establish a hyperglycemic rat model of insulin resistance.The gavage dose of the model group was 0.9%sodium chloride solutionn,the gavage dose of the Shiwei Xiaoke capsule positive drug group was 1.32 g/kg,and the gavage dose of the Huangqi Mulberry Ye Yuzhu granule low,middle and high dose groups were 1.25,2.5 and 7.5 g/kg.Continuous administration for 30 days,The contents of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in peripheral blood and glycogen,free fat acid(FFA),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-PX)in liver were determined by colorimetry,the mRNA and protein expressions of Acetyl-coa carboxylase 1(ACC1),fatty acid synthase(FASN),stearoyl-CoA desaturase 1(SCD1)and glucose transporter2(GLUT2)in rat liver were detected by RT-PCR and Western blot.Results Compared with the blank group,ALT,AST,MDA,FFA,GLUT2 were significantly increased in the model group;the levels of SOD,liver glycogen,GSH-Px,ACC1,FASN,SCD1 were significantly decreased(P<0.05,P<0.01).Compared with the model group,the levels of ALT,AST,MDA and GLUT2 were significantly decreased in the Shiwei Xiaoke group and the low,medium and high dose groups of Sangqi Yiqi Yangyin Fomula;the levels of SOD,liver glycogen,GSH-Px,ACC1,FASN and SCD1 were significantly increased(P<0.05,P<0.01).FFA was significantly decreased in the medium and high dose groups of Sangqi Yiqi Yangyin Fomula(P<0.05,P<0.01).Conclusion Sangqi Yiqi Yangyin Fomula can regulate the disorder of hepatic glucose and lipid metabolism,relieve oxidative stress,and prevent liver injury in rats,and the mechanism may be related to the inhibition of ACC1/FASN/SCD1 pathway and GLUT2 gene and protein expression.
作者
李丽
刘佳琪
冯颖童
扈觐玺
姜斯佳
高晶
贾岚
王景霞
LI Li;LIU Jiaqi;FENG Yingtong;HU Jinxi;JIANG Sijia;GAO Jing;JIA Lan;WANG Jingxia(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《环球中医药》
CAS
2023年第7期1294-1300,共7页
Global Traditional Chinese Medicine
基金
国家重点研发计划(2018YFC1706803)。
关键词
桑芪益气养阴方
气阴两虚证
胰岛素抵抗
氧化应激
肝脏糖脂代谢
Sangqi Yiqi Yangyin Fomula
Qi and Yin deficiency syndrome
Insulin resistance
Oxidative stress
Hepatic glucose and lipid metabolism
作者简介
李丽(1996-),2020级在读硕士研究生。研究方向:中药基础理论。E-mail:1527874193@qq.com;通信作者:王景霞(1976-),博士,教授,博士生导师。研究方向:中药药性理论。E-mail:wjx20131210@163.com;刘佳琪,硕士研究生;冯颖童,硕士研究生;扈觐玺,硕士研究生;姜斯佳,博士研究生。
