糖肾清保护糖尿病肾病大鼠肾功能的作用机制研究

【作者】 曹丽娟；

【导师】 孟凤仙；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2010， 硕士

【摘要】 糖尿病肾病是糖尿病常见的微血管并发症之一,也是导致糖尿病患者死亡的原因之一。近年来,随着糖尿病的发病率逐年上升,糖尿病肾病的发病率也呈上升趋势。因此,保护糖尿病患者的肾功能,有效地延缓糖尿病肾病的病程进展,提高糖尿病肾病患者的生存质量,已经成为了今天国内外医学界关注的焦点,本论文将中西医对糖尿病肾病的认识进行了较为全面的概述,及通过动物实验研究探讨了中药糖肾清保护糖尿病肾病大鼠肾功能的作用机制。1.文献综述查阅古今中医有关糖尿病肾病的文献资料,对其中医病名、病因病机、辨证论治及相关的临床和实验研究进行探讨,同时将西医对糖尿病肾病的治疗进展作了总结,鉴于血管紧张素转换酶抑制剂在糖尿病肾病治疗中所起的重要作用,所以将血管紧张素在糖尿病肾病发病机制中现代研究进展做了系统总结分析。2.实验研究目的：探讨中药糖肾清保护糖尿病肾病大鼠肾功能的作用机制。方法：用链尿佐菌素和四氧嘧啶分别将SD大鼠和wistar大鼠诱发成糖尿病大鼠模型,72h后测血糖,将符合要求的大鼠按随机血糖值,随机分为5组,即模型组、糖肾清高剂量组、糖肾清中剂量组、糖肾清低剂量组、卡托普利组,同时设正常对照组,第3周随机选取每组10只大鼠,用代谢笼收集24h尿液,检测24h尿蛋白,24h尿蛋白排泄增多,提示糖尿病大鼠已有糖尿病肾病的表现,各组大鼠连续灌胃给药,对链尿佐菌素大鼠模型动态观察24h尿量、尿蛋白、肾功能、总胆固醇和体重变化,并对肾组织进行光镜和电镜观察,对四氧嘧啶糖尿病肾病大鼠模型于造模6w后收集24h尿液,测定24h尿量、24h尿蛋白总量及24h尿β2-微球蛋白,同时测定血浆血管紧张素Ⅱ含量和血浆非酶糖化终产物。结果：糖肾清颗粒可明显降低模型大鼠24h尿量和尿蛋白的排泄量,改善肾脏高过滤状态,降低血清总胆固醇含量,与模型组比较差异有统计学意义(P<0.05或P<0.01)；糖肾清可使模型大鼠肾小球和肾小管间质病变较模型组明显减轻,与模型组比较,具有统计学意义(P<0.05或P<0.01)；糖肾清能够降低模型大鼠的尿β2微球蛋白、血浆非酶糖化终产物含量和血浆血管紧张素Ⅱ含量,与模型组比较具有统计学意义(P<0.05或P<0.01)。结论：糖肾清具有益肾滋阴固精、祛瘀解毒降浊的功效,通过观察糖肾清对糖尿病肾病大鼠的干预效果,证明糖肾清可以通过下调血浆血管紧张素Ⅱ、纠正脂代谢紊乱、减少糖化终产物等途径,达到改善肾脏的血流动力学、抑制细胞因子的产生、抑制细胞外基质的增多、阻止肾脏固有细胞的破坏等目的,从而保护肾小球的滤过屏障、减轻肾小管间质病变、减轻肾脏肥大,实现其对糖尿病肾病大鼠肾功能的保护作用。更多还原

【Abstract】 Diabetic nephropathy is a common microvascular complication of diabetes, meanwhile, it is the leading cause of death of diabetic patients. In recent years, with the incidence of diabetes increased year by year, the incidence of diabetic nephropathy is also on the rise, therefore, the protection of diabetic kidney function, effectively delaying the progression of diabetic nephropathy and improving the quality of life of patients with diabetic nephropathy has become the focus of medical profession attention at home and abroad.This thesis comprehensively overview the understanding of diabetic nephropathy on western medicine and taditional chinese mediciine, and disguss protective effect machnism of rats in diabetic nephropathy from Tang Shen Qing (a priscreption on herbal medicine) according to the animals basic resrech.1:Literature ReviewAccess to ancient and modern Chinese literature related to diabetic nephropathy, Study its Chinese name of disease, pathogenesis, syndrome differentiation and related clinical and experimental research, meanwhile, summerize progress of the Western medicine treatment on diabetic nephropathy, in view of angiotensin converting enzyme inhibitors in the treatment of diabetic nephropathy playing an important role,so the modern research improvements on pathogenesis of diabetic nephropathy from angiotensin converting enzyme have been comprehensively summerised and analysed.2:Experimental studyObjective:To study the protective effects of Tang Shen Qing on Diabetic nephropathyMethods:By streptozotocin and alloxan on the establishment of SD rats and wistar rat model of diabetic nephropathy, Rats in meeting the requirements by random blood glucose levels were randomly divided into five groups, namely the model group, Tang Shen Qing lofty dose group, Tangshen Qing middle dose group, Tang Shen Qing low dose group, captopril group. At the same time,It had been set up normal control group,10 rats in each group were randomly selected on the third week,24h urine were collected with metabolic cages,and yet,24h urinary protein were tested. The increasing of the urinary protein excretion suggested the diabetic nephropathy performance of the rats in diabetes.the rats continuously administered orally, rats in streptozotocin diabetic nephropathy model has been had a dynamic of the changes of 24h urine volume, urine protein, kidney function, cholesterol and body weight, and another observation of kidney tissue with light and electron microscopy. After 6 weeks,24h rat urine of alloxan diabetic nephropathy rat model volume urine ware collected,and yet,24h urinary total protein, p2-microglobulin, and plasma angiotensin II levels and plasma non-enzymatic glycation end products were messured.Results:Tang Shen Qing can significantly reduce modle rats both 24h urine volume and urinary protein excretion volume, improve renal high filtration state, lower serum total cholesterol.,the diffrences has statistical meaning (P<0.05 or P< 0.01); Tang Shen Qing can clear renal glomerular and tubulointerstit-ial lesions of model rats significantly compared with model group, it has statistical significance (P<0.05 or P<0.01); Tang Shen Qing makes (32-microglobulin in urine, serum, nonenzymatic glycation end prod-ucts and angiotensinⅡof the model rats significantly reduced. Compared with the model group it is 英文摘要#7statistical significant (P<0.05 or P<0.01).Conclusion:Tang Shen Qing have the functions of enhancing the kidney yin, strenthing the kidneyessence, and getting rid of the blood stasis and detoxification from inner body. With observation of theeffect of Tang Shen QIing interference on Diabetic Nephropathy of rats, it proves that the combination ofvarious drugs can lower angiotensin II, correct metabolic abnormalities and reduct of AGEs,so as toimprove renal blood flow mechanics, inhibit the cytokine production, Inhibit the increase in extracellularmatrix and so on, all in all,it achieves the effects of the protection of renal function of rats with diabeticnephropathy.Key words:diabetic nephropathy;Tang Shen Qing;renal function;mechanism research更多还原