甲状腺激素对2型糖尿病大鼠脂代谢、氧化应激、炎症及血清Alarin水平的影响

Influence of thyroid hormones on lipid metabolism,inflammation,oxidative stress and serum Alarin level in rats with type 2 diabetes mellitus

目的研究甲状腺激素(TH)是否通过调控氧化应激(OS)、炎症及血清Alarin水平改善2型糖尿病(T2DM)大鼠的脂代谢。方法建造T2DM大鼠模型。雄性SD大鼠共48只,按照随机化原则,分为6组:正常对照(NC)组、糖尿病(DM)组、以左甲状腺素钠(LT4)低剂量治疗的糖尿病(DM+LT4-L)组、以LT4中剂量治疗的糖尿病(DM+LT4-M)组、以LT4高剂量治疗的糖尿病(DM+LT4-H)组、以辛伐他汀治疗的糖尿病(DM+SVT)组。每组8只分别用相应的药物灌胃8周,检测空腹血糖、血脂、肝功能、甲状腺激素、炎性因子[肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)]、白介素-1β(IL-1β)、OS指标[过氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)]以及血清Alarin水平。结果DM组大鼠表现出较高的体重,相对于NC组,其亦具有高血糖[空腹血糖(FBG)升高]、高血脂[三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)上升,高密度脂蛋白(HDL)降低]、肝功能异常[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)增高]、甲状腺功能减退[三碘甲腺原氨酸(T3)、甲状腺素(T4)下降;促甲状腺激素(TSH)上升]、高炎症(TNF-α、IL-6、IL-1β明显升高)、OS(MDA上升、SOD、GSH-PX降低)、高Alarin的特性(P<0.05);服用LT4后,大鼠体重及上述血清学参数较DM组有不同程度的改进(P<0.05)。结论LT4可能通过改进糖尿病大鼠的炎症、OS以及Alarin水平调理脂代谢。

Objective To explore the regulatory effects of thyroid hormones(THs)on improving lipid metabolism in rats with type 2 diabetes mellitus(T2DM)by regulating oxidative stress(OS),inflammation and serum Alarin level.Methods A rat T2DM model was established.A total of 48 male Sprague–Dawley(SD)rats were randomly divided into six groups:NC group(normal rats with blank control),DM group(T2DM rats with blank control),DM+LT4-L group(T2DM rats treated with low-dose levothyroxine[LT4]sodium),DM+LT4-M group(T2DM rats treated with medium-dose LT4 sodium),DM+LT4-H group(T2DM rats treated with high-dose LT4 sodium)and DM+SVT group(T2DM rats treated with simvastatin[SVT]),with 8 rats per group.After oral gavage of corresponding drugs for 8 weeks,fasting blood glucose(FBG),blood lipids,liver function,THs,inflammatory factors(tumor necrosis factorα[TNF-α],interleukin-6[IL-6],IL-1β),OS indicators(superoxide dismutase[SOD],malondialdehyde[MDA],glutathione peroxidase[GSH-PX])and serum Alarin level were recorded and compared.Results Rats in the DM group showed a higher body weight.Compared with those of the NC group,rats in the DM group presented hyperglycemia(elevated FBG),hyperlipidemia(elevated triacylglycerol[TG],total cholesterol[TC]and low-density lipoprotein protein[LDL],and decreased high-density lipoprotein[HDL]),abnormal liver function(elevated alanine transaminase[ALT]and aspartate transaminase[AST]),hypothyroidism(decreased triiodothyronine[T3]and thyroxine[T4],and elevated thyroid-stimulating hormone[TSH]),high-level inflammation(elevated TNF-α,IL-6 and IL-1β),OS(elevated MDA and decreased SOD and GSH-PX),and higher serum Alarin level(P<0.05).Administration of LT4 relieved the above-mentioned body weight and serological parameters than those of DM group(P<0.05).Conclusion LT4 may adjust lipid metabolism by amending inflammation,OS and serum Alarin level in T2DM rats.