Department of Internal Cardiovascular, The Second Hospital of Dalian Medical University, Dalian 116027, P.R. China.
Department of Endocrine, The Second Hospital of Dalian Medical University, Dalian 116027, P.R. China
Biosci Rep. 2019 Jul 5;39(7). doi: 10.1042/BSR20182371. Print 2019 Jul 31.
Type II diabetes mellitus (T2DM), a persistent metabolic disorder, is primarily characterized by insulin resistance, relative insulin deficiency and dyslipidemia. Here, we aimed to investigate whether different doses of atorvastatin (ATV) affect rats with T2DM. A total of 110 Sprague-Dawley rats were successfully established as T2DM models. First, the total cholesterol, triglyceride (TG), high-/low-/very-low-density lipoprotein cholesterol (HDL-c/LDL-c/VLDL-c), alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr), apolipoprotein Al (ApoA1) and apolipoprotein B (ApoB) levels in rat serum were analyzed. In addition, cholesteryl ester transfer protein (CETP) and retinol-binding protein 4 (RBP4) were also measured. Then, the incidence of adverse reactions was noted. Finally, the pathological study of liver and pancreatic tissues was performed. Rats administered ATV at the doses of 40 and 80 mg/(kg·day) showed down-regulated TG, LDL-c, ApoB, CETP and RBP4 levels yet up-regulated HDL-c and ApoAl levels. Rats administered ATV at a dose of 80 mg/(kg·day) exhibited a higher incidence of adverse reactions and higher ALT and AST levels but lower BUN and Cr levels, which might affect liver and kidney function. Rats administered ATV at the doses of 40 and 80 mg/(kg·day) demonstrated significantly improved liver injury and pancreatic injury induced by T2DM. These data revealed that ATV could improve the lipid metabolism in T2DM rats and 40 mg/(kg·day) may serve as the optimal dose for the reduction of lipid levels and the incidence of adverse effects.
2 型糖尿病(T2DM)是一种持续的代谢紊乱,主要表现为胰岛素抵抗、相对胰岛素缺乏和血脂异常。在这里,我们旨在研究不同剂量阿托伐他汀(ATV)是否会影响 T2DM 大鼠。总共成功建立了 110 只 Sprague-Dawley 大鼠作为 T2DM 模型。首先,分析了大鼠血清中的总胆固醇、甘油三酯(TG)、高/低/极低密度脂蛋白胆固醇(HDL-c/LDL-c/VLDL-c)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血尿素氮(BUN)、肌酐(Cr)、载脂蛋白 A1(ApoA1)和载脂蛋白 B(ApoB)水平。此外,还测量了胆固醇酯转移蛋白(CETP)和视黄醇结合蛋白 4(RBP4)。然后,注意不良反应的发生率。最后,进行了肝和胰腺组织的病理研究。给予 40 和 80mg/(kg·day)剂量 ATV 的大鼠表现出 TG、LDL-c、ApoB、CETP 和 RBP4 水平下调,而 HDL-c 和 ApoAl 水平上调。给予 80mg/(kg·day)剂量 ATV 的大鼠不良反应发生率较高,ALT 和 AST 水平较高,但 BUN 和 Cr 水平较低,这可能会影响肝肾功能。给予 40 和 80mg/(kg·day)剂量 ATV 的大鼠显著改善了 T2DM 引起的肝损伤和胰腺损伤。这些数据表明,ATV 可以改善 T2DM 大鼠的脂质代谢,40mg/(kg·day)可能是降低血脂水平和不良反应发生率的最佳剂量。