Suman Rajesh Kumar, Ray Mohanty Ipseeta, Borde Manjusha K, Maheshwari Ujwala, Deshmukh Y A
Department of Pharmacology, MGM Medical College, Kamothe, Navi Mumbai 410209, India.
Department of Pathology, MGM Medical College, Kamothe, Navi Mumbai 410209, India.
Adv Pharmacol Sci. 2016;2016:9463476. doi: 10.1155/2016/9463476. Epub 2016 Jan 6.
Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.
背景。全球范围内,代谢综合征与糖尿病并存的发病率呈上升趋势。目的。本研究旨在建立一种独特的动物模型,该模型能模拟糖尿病和代谢综合征患者的病理特征,适用于药物的药理学筛选。材料与方法。采用高脂饮食(HFD)与低剂量链脲佐菌素(STZ)(30、35和40mg/kg)联合使用,在Wistar大鼠中诱导糖尿病背景下的代谢综合征。结果。40mg/kg的STZ产生了持续性高血糖,因此选择该剂量用于诱导糖尿病的研究。在建立的糖尿病合并代谢综合征模型中,模拟了代谢综合征的各种成分,如血脂异常(甘油三酯、总胆固醇、低密度脂蛋白胆固醇升高,高密度脂蛋白胆固醇降低)、糖尿病(血糖、糖化血红蛋白、血清胰岛素和C肽)和高血压(收缩压)。与正常对照组大鼠相比,高脂糖尿病组(HF-DC)除了出现明显的心脏损伤外,还观察到动脉粥样硬化指数、炎症(高敏C反应蛋白)、肝肾功能下降。组织病理学评估证实,与正常对照组相比,高脂糖尿病组心脏、胰腺、肝脏和肾脏存在水肿、坏死和炎症。结论。本研究建立了一种独特的以糖尿病为主要成分的啮齿动物代谢综合征模型。