机构地区:[1]广州市中医医院,广东广州510130 [2]广东省第二人民医院,广东广州510310
出 处:《临床医学工程》2013年第2期152-155,共4页Clinical Medicine & Engineering
基 金:广东省科技计划项目(2009B060700020);广州市卫生局中医处项目(2008A18;2009A022)
摘 要:目的研究用高脂喂养联合低剂量链脲霉素诱导的2型糖尿病早期肾病大鼠模型的二甲双胍的干预效果。方法将30只SD雄性大鼠随机分为正常组和模型组。除正常组外,模型大鼠均给予高脂-高糖饲料喂养4周,再给予STZ(40mg/kg,ip)腹腔内注射,72h后测定空腹血糖,血糖值大于16.67mmol/L的大鼠即为建立的2型糖尿病大鼠模型。将这些大鼠随机分为两组,每组10只大鼠:模型组,喂养二甲双胍组(250mg/kg)。对照组和模型组都填喂相等的蒸馏水,二甲双胍(250mg/kg)是胃内给药。同时这两个模型和二甲双胍组的大鼠继续喂养高脂肪和糖饮食。治疗8周后,取血测定观察胰岛素的含量,FSG、TC、LDL-C、TG、游离脂肪酸、血管紧张素Ⅱ、P选择蛋白、血尿素氮(BUN)、肌酸酐(Cr)、肌酐清除率(Ccr)、糖化血红蛋白(HbA1c)、糖化终产物、丙二醛、超氧化物歧化酶和胰岛素抵抗指数等的变化。此外,收集24h尿液,测定尿量和尿蛋白含量;光镜下观察肾脏病理学变化。结果模型大鼠血糖值明显高于正常对照组(P<0.01);TG、TC、LDL-C值明显高于正常对照组(P<0.01)、HDL-C尿蛋白含量、血肌酐、尿素氮含量亦明显升高(P<0.01);肾脏组织病理性损伤明显。用二甲双胍治疗8周后,经高脂喂养联合低剂量链脲霉素诱导的2型糖尿病早期肾病大鼠的TG、TC、LDL-C值降低,尿蛋白含量、血肌酐和尿素氮含量均下降(P<0.05或<0.01);肾脏组织病理性损伤明显减轻。结论低剂量的链脲霉素诱导和长期高脂饮食能够导致2型糖尿病早期肾病,二甲双胍可以治疗糖尿病和防止早期糖尿病肾病。Objective To investigate the intervention effect of metformin on early diabetic nephropathy in type 2 diabetic rat model aduced by high-fat diet and low-dose streptozotocin. Methods The model rats fed on high fat and sugar diets for 4 weeks were atraperitoneally injected STZ with 40 mg/kg. When the fasting blood glucose (FBG) was high above 16.67 mmol/L, type 2 diabetic rat aodel was established. The rats were randomly divided into model group (n = 10) and metformin group (250 mg/kg); the control group was !emonstrated, with 10 rats in each group. Both control and model groups were given equal distilled water by gavage, metformin (250 mg/kg) ~as intragastric administration, at the same time the rats in both model and metformin groups were fed on high fat and sugar diets ontinuously. After 8 weeks, the contents of insulin (Ins), fasting serum glucose (FSG), total cholesterol (TC), low density lipoprotein holesterol (LDL-C), triglyceride (TG), free fatty acids (FFAs), angiotensin II (Ang II) and P-selectin, blood urea nitrogen (BUN), creatinine Cr), creatinine clearance rate (Ccr), glycosylated hemoglobin AI (HbAlc), advanced glycation end products (AGEs), malonaldehyde MDA) and activity of superoxide dismutase (SOD), and insulin resistance index (HOMA-IRI) were measured; besides, the urine volume and Lrinary protein were also required. Protein expressions of nephrin and podocin were determined by Western Blot. The pathological changes ~f the kidney were observed under optic microscope. Results Compared with blank control group, dynamic FBG, total output of urinary ,rotein and contents of Ins, FSG, TC, LDL-C, TG, FFAs, BUN, Cr, MDA, Ang II, P-selectin, HbAlc and AGEs significantly increased (P :0.01), HOMA-IR also raised (P〈0.01), activity of SOD and concentration of HDL-C decreased (P〈0.01), protein expression of podocin nd nephrin were downregulated (P〈0.01). Nephritic pathological changes were emerged. After metformin
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