毛蕊异黄酮改善2型糖尿病模型大鼠的糖脂代谢紊乱和代谢相关脂肪性肝病症状  

Calycosin ameliorates glycolipid metabolism disorder and metabolic as⁃sociated fatty liver disease symptoms in type 2 diabetic rats

作　　者：侯瑞英[1] 吴冬梅[1] 焦伟杰[1] 汪坤[1] 杜蕾[1] 吴桂月[1] 韩竞 赵旭[1] HOU Rui-ying;WU Dong-mei;JIAO Wei-jie;WANG Kun;DU Lei;WU Gui-yue;HAN Jing;ZHAO Xu(Department of Pharmacy,Henan Province Hospital of Traditional Chinese Medicine,Zhengzhou 450002,China)

机构地区：[1]河南省中医院药学部,河南郑州450002

出　　处：《中国病理生理杂志》2021年第11期1965-1971,共7页Chinese Journal of Pathophysiology

基　　金：河南省中医药科学研究专项课题(No.20-21ZY2212);河南省中医药拔尖人才培养项目(豫卫中医函〔2021〕15号)。

摘　　要：目的:探讨毛蕊异黄酮(calycosin,CAL)对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠的糖脂代谢紊乱、胰岛素抵抗、肝脂肪变性和肝损伤的影响,并分析其机制。方法:先将SD大鼠随机分为普通饲料(nor-mal chow diet,NCD)饲养组(n=14)和高脂-高糖饲料(high fat-high sugar diet,HFSD)饲养组(n=31),5周后,HFSD组大鼠腹腔注射50 mg/kg链脲佐菌素,NCD组给予等体积柠檬酸缓冲液。注射后3 d,将空腹血糖水平>200 mg/dL的HFSD组大鼠(n=28)随机分为模型(model)组及model+低、中和高剂量CAL组,每组7只大鼠,用HFSD饲养16周;其中model+低、中和高剂量CAL组大鼠分别灌胃给药10、20和40 mg/kg CAL,每天1次,持续16周;NCD组大鼠分为正常对照(normal control,NC)组(n=7)和NC+高剂量CAL组(n=7),用NCD饲料饲养16周。给药方案结束后,收集大鼠血液样本和肝组织,并分别进行生化、组织学和Western blot检测。结果:生化结果显示,与model组比较,model+低、中和高剂量CAL组血清中葡萄糖、胰岛素、甘油三酯、总胆固醇、低密度脂蛋白胆固醇、丙氨酸转氨酶和天冬氨酸转氨酶水平及肝组织中白细胞介素6(IL-6)、IL-1β和肿瘤坏死因子α(TNF-α)水平均显著降低(P<0.05,P<0.01),血清中高密度脂蛋白胆固醇水平显著升高(P<0.05,P<0.01)。组织学结果显示,与model组比较,model+低、中和高剂量CAL组肝脂肪变性和肝脂蓄积均显著减轻(P<0.05,P<0.01)。Western blot结果显示,与model组比较,model+低、中和高剂量CAL组肝组织中p-IRS-1(Ser307)和p-Akt(Ser473)表达和NF-κB p65核转位均显著降低(P<0.05,P<0.01)。结论:CAL可能通过恢复胰岛素信号转导和减弱NF-κB信号通路活性抑制T2DM大鼠的胰岛素抵抗、恢复糖脂代谢稳态、改善肝脂肪变性和肝脂蓄积并减轻肝损伤。AIM:To investigate the effects of calycosin(CAL)on glycolipid metabolism disorder,insulin re-sistance,hepatic steatosis and liver injury in type 2 diabetes mellitus(T2DM)rats,and to analyze its mechanism.METHODS:SD rats were randomly divided into normal chow diet(NCD)group(n=14)and high fat-high sugar diet(HFSD)group(n=31).Five weeks later,the rats in HFSD group was intraperitoneally injected with 50 mg/kg streptozoto-cin,and the rats in NCD group was given equal volume of citrate buffer.Three days after injection,the rats in HFSD group with FBG>200 mg/dL(n=28)were randomly divided into model group and model+low-dose,medium-dose and high-dose CAL groups,with 7 rats in each group,and fed HFSD for 16 weeks.The rats in model+low-dose,medium-dose and high-dose CAL groups were given 10,20,and 40 mg/kg CAL by gavage once daily for 16 weeks,respectively.The rats in NCD group were divided into normal control(NC)group(n=7)and NC+high-dose CAL group(n=7),and were fed with NCD diet for 16 weeks.At the end of the administration regimen,blood samples and liver tissues were collected for bio-chemical,histological,and Western blot.RESULTS:Biochemical results showed that compared with model group,the serum levels of glucose,insulin,triglyceride,total cholesterol,low density lipoprotein cholesterol,alanine aminotransfer-ase and aspartate aminotransferase,and the levels of interleukin-6(IL-6),IL-1βand tumor necrosis factor-α(TNF-α)in liver tissues in model+low-dose,medium-dose and high-dose CAL groups were significantly decreased(P<0.05,P<0.01),while,the serum level of high density lipoprotein cholesterol was significantly increased(P<0.05,P<0.01).Compared with model group,hepatic steatosis and lipid accumulation in model+low-dose,medium-dose and high-dose CAL groups were significantly reduced(P<0.05,P<0.01).Compared with model group,the protein levels of p-IRS-1(Ser307)and p-Akt(Ser473)and nuclear translocation of NF-κB p65 in liver tissues in model+low-dose,medium-dose and high-dose CAL groups were significantly decreased(P<

关 键 词：毛蕊异黄酮 2型糖尿病 胰岛素抵抗 肝脂肪变性 NF-ΚB信号通路 

分 类 号：R589[医药卫生—内分泌] R285.5[医药卫生—内科学]