摘要目的 观察桂皮醛抗糖尿病的效果并探讨其药理机制.方法 将清洁级雄性Wistar大鼠40只分为正常对照组(8只,普通饮食),其余32只大鼠予高脂高糖饮食、链脲佐菌素,造成2型糖尿病成模大鼠(24只),分为糖尿病对照组、二甲双胍治疗组(200 mg·kg-1·d-1)和桂皮醛治疗组(40 mg·kg-1·d-1),每组8只.经药物干预4周后测各组体质量、空腹血糖、血脂、空腹血胰岛素并计算胰岛素抵抗指数(HOMA-IR),采用Western blot对血清及组织的视黄醇结合蛋白4(RBP4)、葡萄糖转运载体4(GLUT4)蛋白水平进行分析,免疫组织化学染色分析组织p85α和胰岛素受体底物1(IRSI)蛋白表达水平.结果 与糖尿病对照组比较,桂皮醛降糖、降脂、提高胰岛素敏感性效果明显[空腹血糖:(22.7±4.0)比(7.5±1.5)mmol/L;甘油三酯:(1.53±0.13)比(0.77±0.15)mmol/L;HOMA-IR:8.0±3.0比61.2±12.1,P<0.01];糖尿病组血清RBP4升高了1.68倍,GLUT4蛋白水平与正常对照组比较下调了33%～44%,差异有统计学意义(P<0.05);与糖尿病组比较,桂皮醛明显降低了(28.6%)血清RBP4水平(P<0.05),下调肌肉p85a蛋白表达(0.51±0.05比0.43±0.04,P<0.05),同时上调IRSl蛋白表达(0.52±0.05比0.03±0.06,P<0.05),肝脏、肌肉和脂肪组织的GLUT4蛋白表达升高.结论 桂皮醛具有良好的降糖调脂、提高胰岛素敏感性的效果,其药理机制与降低血清RBP4水平以及调节肌肉组织p85α和IRSI蛋白表达有关.

abstractsObjective To evaluate the effect of cinnamaldehyde (Cin) on glucose and lipids profiles in rats with type 2 diabetes mellitus (T2DM), subsequently to investigate its molecular mechanisms for reducing insulin resistance (IR). Methods Rat models of T2DM were established by combination of high-fat diet induction and intraperitoneal injection of low-dose streptozotocin. Rats were divided into the normal control group (NC), T2DM group, T2DM + mefformin (Met) group and T2DM +Cin group. After four weeks of treatment, blood was extracted for measurement of serum glucose, insulin and lipids. Western blot was used to detect the serum or tissue retinol-binding-protein 4 (RBP4) and glucose transporter 4 (GLUT4) protein levels, Immunohistochemistry was applied to detect the expression of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85 alpha (p85α) in gastrocnemius muscles. Results Cin displayed promising hypolipidemic, anti-hyperglycemic, and insulin sensitizing functions (FPG: (7.5±1.5) vs (22.7±4.0) mmol/L; TG: (0.77±0.15) vs(1.53±0.13) mmol/L; HOMA-IR:8.0±3.0 vs 61.2±12.1, P <0.01) compared with the T2DM group. Serum RBP4 levels in Cin treated rats were markedly lowered, and the protein contents of tissue GLUT4 were significantly up-regulated. Also, Cin increased the expression of IRS-1 in gastrocnemius muscles of T2DM rats (0.52±0.05 vs 0.63±0.06, P < 0.05), whereas notably decreased the expression of p85α (0.51±0.05 vs 0.43±0.04, P<0.05). Conclusion Cinnamaldehyde can improve glucose and lipids metabolism in type 2 diabetic rats and its pharmacological mechanisms are at least partially related with reducing serum RBP4 concentration, increasing IRS-1 and decreasing of p85α in gastrocnemius muscles.