本文關鍵詞： 硫辛酸 AGEs 氧化應激 RAGE 糖尿病大鼠　出處：《濟南大學》2014年碩士論文　論文類型：學位論文

【摘要】：目的：氧化應激對于糖尿病腎病發(fā)病的作用備受關注。試驗表明，抗氧化劑能對抗DM中的氧化損傷。本研究主要目的是探究硫辛酸對DN大鼠模型AGEs及氧化應激的影響，并觀察腎臟RAGE的表達情況，為糖尿病腎病患者的早期抗氧化干預提供依據。 方法：30只Wistar大鼠，隨機選取6只作為對照組（A組）,其它24只大鼠高糖高脂飲食8w，鏈脲佐菌素（STZ）兩次腹腔注射造模，糖尿病腎病大鼠按血糖水平隨機分為糖尿病腎病組（B組）和LA組（C組），分別給予生理鹽水和LA(50mg.kg-1.d-1)1ml腹腔注射4周。測定各組體重，隨機血糖，24小時尿白蛋白，空腹血糖，甘油三酯，總膽固醇，HDL-C，LDL-C，丙二醛，GSH-Px，超氧化物歧化酶，AGEs，GHbA1c，腎臟RAGE。 結果：1、三組大鼠體重、隨機血糖的變化：剔出因感染死亡和造模未成功的大鼠，入選糖尿病腎病造模成功鼠為16只，按血糖水平隨機分為糖尿病腎病組（B組）和LA組（C組），各8只。造模組大鼠高脂飲食8周后較正常組大鼠體重明顯增加，此后B組及C組體重均有所下降，，實驗結束時，糖尿病腎病組大鼠體重顯著低于正常組，LA組與正常組無顯著性差異，均未達到STZ注射前的水平；兩組大鼠血糖在STZ干預前無差異，STZ兩次注射1周后B組出現持續(xù)高血糖癥，隨機血糖平均16.82±7.68mmol/l，LA組隨機血糖平均13.36±5.71mmol/l。2、三組大鼠血AGEs、胰島素抵抗等變化：與A組比較，B、C兩組AGEs、糖化血紅蛋白、空腹血糖、FINS及胰島素抵抗指數（HOMA-IR）均升高，IAI下降，差異顯著（P0.05或P0.01）,提示胰島素抵抗；與B組大鼠比較，C組大鼠血AGEs、糖化血紅蛋白、空腹血糖、FIN及HOMA-IR下降（P0.05），IAI升高（P0.05）。3、三組大鼠血脂、24小時尿蛋白水平的變化：與A組比較，B組血總膽固醇、甘油三酯、LDL-C、24h尿蛋白均顯著性升高（P0.05或P0.01），提示脂代謝、腎功能紊亂；與B組比較，C組上述指標均下降（P0.05）；三組大鼠HDL-C無明顯變化。4．三組大鼠氧化應激指標的變化：與A組比較，B組大鼠血MDA升高，差異有顯著性（P0.05）,而SOD、GSH-Px均下降，與B組比較，C組血MDA下降，SOD、GSH-Px均增加，其中SOD的差異有顯著性。5．在組織RNA樣本純度較高，基本無蛋白質污染的情況下，正常對照組腎臟組織未檢測到RAGE表達，LA組和糖尿病腎病組均檢測到RAGE表達。 結論：糖尿病腎病狀態(tài)下循環(huán)及腎臟晚期糖基化終末產物增多，RAGE表達上調，LA能夠減少氧化應激，抑制糖基化終末產物生成并下調RAGE表達水平，從而改善糖尿病腎病大鼠腎組織結構及腎功能，在糖尿病腎病的防治方面有良好的應用前景。
[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 鹵7.68 mmol / l of random blood glucose. The mean blood glucose in LA group was 13.36 鹵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.
【學位授予單位】：濟南大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R587.2;R692

【參考文獻】

相關期刊論文 前6條

1 代新華;張志利;王文萍;;α-硫辛酸降低糖尿病大鼠氧化應激及對腎臟的保護作用[J];當代醫(yī)學;2011年10期

2 張曉剛;肝脂酶與脂蛋白代謝[J];國外醫(yī)學.臨床生物化學與檢驗學分冊;2002年01期

3 王揚天;趙明;狄紅杰;;糖尿病大鼠腎病變過程中核因子-κB及誘導型一氧化氮合酶的表達[J];醫(yī)學研究生學報;2006年05期

4 舒毅,鐘歷勇;氧化應激與糖尿病[J];東南大學學報(醫(yī)學版);2005年01期

5 蔣偉;劉麗秋;;糖尿病腎病發(fā)病機制研究進展[J];山東醫(yī)藥;2008年10期

6 宋恩峰;劉晶晶;賈汝漢;韋桂蓮;任開明;;2型糖尿病腎病大鼠模型制備研究[J];實用醫(yī)學雜志;2007年18期

本文編號：1483961