褪黑素受体激动剂Neu-p11改善T2DM大鼠的胰岛素抵抗作用研究  

Melatonin receptor agonist Neu-p11 improves insulin resistance in T2DM rats

作　　者：高迎春 岳颖 周珺[1] 马慧萍 张汝学 GAO Ying-chun;YUE Ying;ZHOU Jun;MA Hui-ping;ZHANG Ru-xue(Dept of Pharmacy,the 940th Hospital of Joint Logistics Support Force of PLA,Lanzhou 730050,China;College of Pharmacy,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]解放军联勤保障部队第940医院,全军高原环境损伤防治重点实验室/国家中医药管理局临床中药学重点学科,甘肃兰州730050 [2]兰州大学药学院,甘肃兰州730000

出　　处：《中国药理学通报》2020年第2期221-225,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81173620)。

摘　　要：目的研究褪黑素受体激动剂Neu-p11改善2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠的胰岛素抵(insulin resistance,IR)作用,并预测其可能机制。方法采用长期高脂肪饲养加小剂量链脲佐菌素(STZ,30 mg·kg^-1,ip)诱导雌性大鼠2型糖尿病动物模型,灌胃给药4周后处死,取肝脏组织。采用RT-PCR方法测定大鼠Sirt1、Nrf-1/2、ERRα等相关因子的mRNA表达量;Western Blot法测定PGC-1α、Mfn2的相对表达。测定大鼠INS,计算HOME-IR与ISI。测定大鼠肝脏ATP含量及ATP酶活力。结果与正常组相比,T2DM大鼠发生IR,PGC-1α、Mfn2蛋白表达上调,Sirt1等mRNA表达显著降低,ERRαmRNA表达升高,ATP含量显著减少,ATP酶活力减弱。与模型组相比,Neu-p11低剂量组降低T2DM大鼠INS;改善T2DM大鼠IR;上调大鼠肝脏蛋白和mRNA表达,下调ERRαmRNA的表达,增加大鼠肝脏ATP含量与ATP酶活力。结论褪黑素受体激动剂Neu-p11可能以调节T2DM大鼠肝脏线粒体平衡相关因子,维持线粒体功能正常为机制,改善IR。Aim To study the effect of melatonin receptor agonist Neu-p11 on IR in T2DM rats and to predict its possible mechanism.Methods Long-term high-fat feeding plus low-dose streptozotocin(STZ,30 mg·kg^-1,ip)were used to induce an animal model of type 2 diabetes in female rats.After 4 weeks of intragastric administration,liver tissue was sacrificed.The mRNA expression levels of Sirt1,Nrf-1/2 and ERRαin rats were determined by RT-PCR.The relative expressions of PGC-1αand Mfn2 were determined by Western blot.Rat INS was measured and HOME-IR and ISI were calculated.The liver ATP content and ATPase activity were measured.Results Compared with normal group,T2DM rats developed IR,PGC-1α,Mfn2 protein expression increased,Sirt1 and other mRNA expression decreased significantly,ERRαmRNA expression increased,ATP content decreased significantly,and ATPase activity decreased.Compared with model group,the Neu-p11 low-dose group reduced INS in T2DM rats,improved IR in T2DM rats,up-regulated rat liver protein and mRNA expression,down-regulated ERRαmRNA expression,and increased rat liver ATP content and ATPase activity.Conclusions The melatonin receptor agonist Neu-p11 may improve IR by regulating the mitochondrial balance-related factors in liver of T2DM rats and maintaining normal mitochondrial function.

关 键 词：2型糖尿病 褪黑素 Neu-p11 MFN2 PGC-1Α SIRT1 Nrf-1/2 

分 类 号：R-332[医药卫生] R322.47