硫辛酸对糖尿病肾病大鼠的AGEs及氧化应激影响的实验研究

发布时间：2018-02-02 07:18

本文关键词： 硫辛酸 AGEs 氧化应激 RAGE 糖尿病大鼠　出处：《济南大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：氧化应激对于糖尿病肾病发病的作用备受关注。试验表明，抗氧化剂能对抗DM中的氧化损伤。本研究主要目的是探究硫辛酸对DN大鼠模型AGEs及氧化应激的影响，并观察肾脏RAGE的表达情况，为糖尿病肾病患者的早期抗氧化干预提供依据。方法：30只Wistar大鼠，随机选取6只作为对照组（A组）,其它24只大鼠高糖高脂饮食8w，链脲佐菌素（STZ）两次腹腔注射造模，糖尿病肾病大鼠按血糖水平随机分为糖尿病肾病组（B组）和LA组（C组），分别给予生理盐水和LA(50mg.kg-1.d-1)1ml腹腔注射4周。测定各组体重，随机血糖，24小时尿白蛋白，空腹血糖，甘油三酯，总胆固醇，HDL-C，LDL-C，丙二醛，GSH-Px，超氧化物歧化酶，AGEs，GHbA1c，肾脏RAGE。结果：1、三组大鼠体重、随机血糖的变化：剔出因感染死亡和造模未成功的大鼠，入选糖尿病肾病造模成功鼠为16只，按血糖水平随机分为糖尿病肾病组（B组）和LA组（C组），各8只。造模组大鼠高脂饮食8周后较正常组大鼠体重明显增加，此后B组及C组体重均有所下降，，实验结束时，糖尿病肾病组大鼠体重显著低于正常组，LA组与正常组无显著性差异，均未达到STZ注射前的水平；两组大鼠血糖在STZ干预前无差异，STZ两次注射1周后B组出现持续高血糖症，随机血糖平均16.82±7.68mmol/l，LA组随机血糖平均13.36±5.71mmol/l。2、三组大鼠血AGEs、胰岛素抵抗等变化：与A组比较，B、C两组AGEs、糖化血红蛋白、空腹血糖、FINS及胰岛素抵抗指数（HOMA-IR）均升高，IAI下降，差异显著（P0.05或P0.01）,提示胰岛素抵抗；与B组大鼠比较，C组大鼠血AGEs、糖化血红蛋白、空腹血糖、FIN及HOMA-IR下降（P0.05），IAI升高（P0.05）。3、三组大鼠血脂、24小时尿蛋白水平的变化：与A组比较，B组血总胆固醇、甘油三酯、LDL-C、24h尿蛋白均显著性升高（P0.05或P0.01），提示脂代谢、肾功能紊乱；与B组比较，C组上述指标均下降（P0.05）；三组大鼠HDL-C无明显变化。4．三组大鼠氧化应激指标的变化：与A组比较，B组大鼠血MDA升高，差异有显著性（P0.05）,而SOD、GSH-Px均下降，与B组比较，C组血MDA下降，SOD、GSH-Px均增加，其中SOD的差异有显著性。5．在组织RNA样本纯度较高，基本无蛋白质污染的情况下，正常对照组肾脏组织未检测到RAGE表达，LA组和糖尿病肾病组均检测到RAGE表达。结论：糖尿病肾病状态下循环及肾脏晚期糖基化终末产物增多，RAGE表达上调，LA能够减少氧化应激，抑制糖基化终末产物生成并下调RAGE表达水平，从而改善糖尿病肾病大鼠肾组织结构及肾功能，在糖尿病肾病的防治方面有良好的应用前景。
[Abstract]:Objective: the role of oxidative stress in the pathogenesis of diabetic nephropathy has attracted much attention. The main purpose of this study was to investigate the effects of lipoic acid on AGEs and oxidative stress in DN rat model and to observe the expression of RAGE in kidney. To provide evidence for early anti-oxidation intervention in diabetic nephropathy patients. Methods Twenty Wistar rats were randomly selected as control group (n = 6) and the other 24 rats were treated with streptozotocin (STZ) for 8 weeks. Diabetic nephropathy rats were randomly divided into diabetic nephropathy group (group B) and LA group (group C). Normal saline and LA(50mg.kg-1.d-1)1ml were injected intraperitoneally for 4 weeks. Body weight, 24 hours urinary albumin, fasting blood glucose and triglyceride were measured. Total cholesterol (HDL-C), malondialdehyde (MDA) GSH-Px, superoxide dismutase (SOD) AGES-GHbA1c, kidney RAGE. Results the changes of body weight and blood sugar in the three groups of rats were as follows: the rats died of infection and failed to model, and 16 rats were selected to model diabetic nephropathy. According to the blood glucose level, the rats were randomly divided into two groups: diabetic nephropathy group (n = 8) and LA group (n = 8). The weight of the model group was significantly higher than that of the normal group after 8 weeks of high-fat diet. At the end of the experiment, the body weight of the diabetic nephropathy group was significantly lower than that of the normal group and that of the LA group and the normal group, and did not reach the level before STZ injection. There was no difference in blood glucose between the two groups before the intervention of STZ. The hyperglycemia occurred in group B one week after twice injection of STZ, with a mean of 16.82 卤7.68 mmol / l of random blood glucose. The mean blood glucose in LA group was 13.36 卤5.71 mmol / L. 2. The changes of ages and insulin resistance in blood of three groups were compared with those in group A: ages and glycosylated hemoglobin in group C were compared with those in group A. Fasting blood glucose fins and insulin resistance index (HOMA-IRI) increased and IAI decreased significantly (P 0.05 or P 0.01), indicating insulin resistance. Compared with group B, the levels of ages, glycosylated hemoglobin, fasting blood glucose and HOMA-IR in group C were significantly higher than those in group B (P 0.05). Changes of 24 hour urinary protein level in three groups: compared with group A, total cholesterol and triglyceride LDL-C in group B were compared with those in group A. 24 hours urine protein increased significantly (P0.05 or P0.01), indicating lipid metabolism and renal dysfunction. Compared with group B, the above indexes in group C were decreased (P 0.05). There was no significant change in HDL-C in three groups. 4. The changes of oxidative stress index in three groups: compared with group A, the serum MDA of rats in group B was higher than that of group A, and the difference was significant (P 0.05), while that of SOD in group B was higher than that in group A. Compared with group B, the blood MDA of group C was increased, and the difference of SOD was significant. 5. The purity of RNA samples was higher in group C than in group B. No RAGE expression was detected in normal control group without protein contamination. RAGE expression was detected in LA group and diabetic nephropathy group. Conclusion: in diabetic nephropathy, the increased expression of advanced glycosylation end products in diabetic nephropathy and advanced glycosylation end products can reduce oxidative stress. In order to improve the renal tissue structure and renal function of diabetic nephropathy rats, the production of glycosylation end products was inhibited and the expression of RAGE was down-regulated. It has a good prospect in the prevention and treatment of diabetic nephropathy.
【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R587.2;R692

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