球型脂联素对2型糖尿病大鼠肾脏病变的保护作用研究

发布时间：2019-03-29 17:18

【摘要】：目的:观察球型脂联素对2型糖尿病大鼠肾脏病变中的TGF-β1、Smad3、Smad7等相关因子表达的影响,探讨球型脂联素对2型糖尿病大鼠肾脏病变发生、发展过程中的保护作用机制。方法:将雄性SD大鼠按体质量随机分为正常对照组(NC组)以及模型组。NC组给予普通饲料喂养。模型组给予高糖、高脂饲料喂养,8周后,按30mg/kg分别给予浓度为1%的链脲佐菌素腹腔注射。NC组予等量柠檬酸-柠檬酸钠缓冲液。4周后测空腹血糖均高于16.7mmol/L,并出现DM的临床表现,表明T2DM模型已成功建立。继续饲养6周后检测模型组大鼠尿蛋白阳性,取肾脏进行病理观察,2型糖尿病肾病模型成功建立。造模成功后,将模型组随机分为糖尿病组(DM组)、脂联素组(AD组),AD组给予球型脂联素腹腔注射10ug/kg,每日1次,DM组给予同等量生理盐水腹腔注射每日1次,各组分别于实验第4周、8周、12周末,留取血标本,检测血糖;留取尿标本,检测尿肌酐、尿蛋白;然后取肾脏组织,称重并计算肾重指数。观察病理结果,测定TGF-β1、Smad3、Smad7 m RNA、蛋白表达水平。结果:1.与NC组、AD组相比,DM组同期大鼠空腹血糖、24h尿白蛋白、尿肌酐和肾重/体重显著升高(P0.05);2.TGF-β1、Smad3的表达在DM组中均明显高于NC组与AD组(P0.05);3.Smad7的表达在DM组中均明显低于NC组与AD组(P0.05);结论:1.TGF-β1、Smad3在糖尿病肾病中起致病作用,Smad7起保护作用2.脂联素通过下调TGF-β1、Smad3的表达,上调Smad7的表达,抑制肾脏纤维化,延缓甚至逆转糖尿病肾病的进展。
[Abstract]:Aim: to observe the effect of globular adiponectin on the expression of TGF- 尾 1, Smad3,Smad7 and other related factors in renal lesions of type 2 diabetic rats, and to explore the protective mechanism of globular adiponectin on the occurrence and development of renal pathological changes in type 2 diabetic rats. Methods: male SD rats were randomly divided into normal control group (NC group) and model group according to body weight. NC group was fed with ordinary diet. The model group was fed with high glucose and high fat diet. After 8 weeks, streptozotocin of 1% concentration was injected intraperitoneally according to 30mg/kg. The NC group was given the same amount of citric acid-sodium citrate buffer. 4 weeks later, the fasting blood glucose was higher than 16.7 mmol / L, and the blood glucose of the model group was higher than 16.7 mmol / L after 4 weeks. The clinical manifestations of DM showed that the T2DM model had been successfully established. After 6 weeks of feeding, the urine protein of rats in the model group was detected and the kidney was taken for pathological observation. The model of type 2 diabetic nephropathy was successfully established. After successful establishment of the model, the model group was randomly divided into diabetic group (DM group), adiponectin group (AD group), AD group) received intraperitoneal injection of 10 ug / kg adiponectin once a day, and DM group received the same amount of saline intraperitoneal injection once a day. Blood samples were collected from each group at the 4th week, 8th week and 12th weekend to detect blood glucose. Urine samples were collected, urine creatinine and protein were measured, and kidney tissue was taken to weigh and calculate renal weight index. The expression levels of TGF- 尾 1 and Smad3,Smad7 m RNA, protein were measured. Results: 1. Compared with NC group and AD group, fasting blood glucose, 24-hour urinary albumin, urine creatinine and renal weight / body weight in DM group were significantly higher than those in DM group and AD group (P0.05). 2. The expression of TGF-尾 1 and Smad3 in DM group was significantly higher than that in NC group and AD group (P0.05). The expression of 3.Smad7 in DM group was significantly lower than that in NC group and AD group (P0.05). Conclusion: 1. TGF-尾 1 and Smad3 play a pathogenic role in diabetic nephropathy, and Smad7 play a protective role in diabetic nephropathy. Adiponectin can down-regulate the expression of TGF- 尾 1 and Smad3, up-regulate the expression of Smad7, inhibit renal fibrosis and delay or even reverse the progression of diabetic nephropathy.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R692.9

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