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目的:探讨具有胰岛素抵抗(IR)特征、可用于2型糖尿病(T2DM)肾损害研究的SD大鼠动物模型。方法:采用自制脂肪乳连续10天无灌胃、两次SD大鼠腹腔注射小剂量四氧嘧啶造模,以空腹血糖≥16.7mmol/L、并伴有IR指数升高(Homa-IR≥8.3)为造模成功;观察6周后造模组与对照组大鼠的一般情况、肾脏肥大指数(KHI)、内生肌酐清除率(Ccr)、尿白蛋白排泄率(UAER)以及肾脏病理的改变。结果:造模组15只大鼠中13只造模成功,出现明显的高血糖和IR,并持续至实验观察6周后,造模成功率86.7%;造模组大鼠较对照组KHI显著增高,Ccr及UAER亦显著增高,肾脏病理示肾小球体积明显增大,毛细血管袢开放不良,肾小球基膜增厚,系膜基质增多,系膜增宽。结论:采用脂肪乳灌胃及两次腹腔注射小剂量四氧嘧啶可诱导SD大鼠产生稳定的高血糖IR状态,并出现较典型的类似人类糖尿病肾脏损害的早期临床和病理改变。本方法实验周期短,成模率较高,相对简便经济,可用于T2DM肾损害的实验研究。
OBJECTIVE: To investigate the animal model of SD rats with insulin resistance (IR) character and for the study of renal damage in type 2 diabetes mellitus (T2DM). Methods: The self-made fat emulsion was administered intragastrically for 10 days without any intragastric administration. Two SD rats were injected intraperitoneally with low dose of alloxan, with fasting blood glucose≥16.7mmol / L, accompanied by increased IR index (Homa-IR≥8.3 ) For modeling success. The general situation, KHI, Ccr, urinary albumin excretion rate (UAER) and renal pathology of rats in model group and control group were observed after 6 weeks. change. Results: Thirteen rats in model group were successful in modeling, with obvious hyperglycemia and IR, and continued to observe the experimental 6 weeks after the model success rate of 86.7%; model group rats than the control group KHI significantly Increased, Ccr and UAER also increased significantly, renal pathology showed significantly increased glomerular volume, poor capillary loop open, glomerular basement membrane thickening, mesangial matrix increased, widened mesangium. CONCLUSION: Intravenous fat emulsion and two intraperitoneal injections of alloxan induce the stable IR state of hyperglycemia in SD rats and lead to early clinical and pathological changes that are more typical of human diabetic kidney damage. The method has the advantages of short experimental period, high molding rate, relatively simple and economical, and can be used for experimental research on T2DM renal damage.