【作者】 关慧波；

【导师】 谢宁；

【作者基本信息】 黑龙江中医药大学 ， 中医基础理论， 2008， 博士

【摘要】 目的:观察健脾补肾、益气养阴法对糖尿病肾病大鼠的治疗作用及肾脏基因表达的影响,探讨糖尿病肾损伤的发病机制,揭示中药复方治疗糖尿病肾损伤的作用机理。方法:选用Wistar大鼠,通过高脂高糖饮食加腹腔小剂量注射链脲佐菌素复制糖尿病肾损伤大鼠模型,运用生化、光镜、电镜、免疫组化、逆转录聚合酶链反应等检测手段和方法,观测(1)糖尿病肾损伤大鼠一般状况;(2)24h尿微量白蛋白;(3)肌酐、尿素氮;(4)肾重指数;(5)免疫组化法检测肾脏中转化生长因子1、结缔组织生长因子及血管内皮生长因子表达:(6)逆转录聚合酶链反应检测肾内TGFβ1mRNA、CTGFmRNA表达情况;(7)肾组织病理及超微结构。结果:(1)糖尿病肾损伤大鼠模型复制成功;(2)健脾补肾、益气养阴法能明显改善糖尿病肾病大鼠一般状况,改肾重/体重的比值,减少肌酐、尿素氮等小分子代谢产物,降低尿蛋白排泄;(3)对糖尿病肾病大鼠血管内皮生长因子具有良性调节作用;(4)能下调TGFβ1mRNA、CTGFmRNA的表达;(5)病理结果显示,健脾补肾、益气养阴法能修复糖尿病肾病大鼠肾小球及肾小管的病理损伤,保护肾功能,延缓肾衰竭。结论:(1)糖尿病肾病为本虚标实之证,病及五脏六腑,气血经络,其脏腑虚损以脾肾为著,脾肾两虚是糖尿病肾病病理基础,健脾补肾、益气养阴法,切合本病病机特点,体现了中医辨证论治的整体性,是临床治疗糖尿病肾病的有效良方。(2)健脾补肾、益气养阴法具有良好的治疗糖尿病肾病的作用,改善大鼠一般状况,通过减少肌酐、尿素氮等小分子代谢产物,降低蛋白尿,从而改善糖尿病肾病大鼠的生存状态,改善肾功能,达到防治糖尿病肾病的目的。(3)通过抑制转化生长因子1、结缔组织生长因子及血管内皮生长因子蛋白表达,抑制TGF-β1mRNA、CTGFmRNA表达,从而降低蛋白尿,抑制肾小球细胞及肾间质成纤维细胞合成ECM,抑制肾脏肥大,最终延缓了疾病的进展。(4)能修复糖尿病肾病大鼠肾小球及肾小管的病理损伤,保护肾功能。更多还原

【Abstract】 In recent years, the incidence of the Diabetes mellitus rises gradually in the world, and the harmfulness makes people pay attention to it more and more. The Diabetes nephropathy is one of the familiar capillaries complicationses of the dibaetes.The pathogenesis of DN involves many kinds of factors. The relation among TGFβ1, CTGF, VEGF and nephropathy has already become a focus in international researeh. It has been approved that TGF(31,CTGF plays an important role in the occurrenecen and development of DN.CTGF is the downstream medium of TGFβ1, involve in accelerating cell matrix synthesis function of TGFβ1. VEGF is the specific mitogen of endothelial cell, and it can promote endothelial cell proliferation and neonatal blood vessel formation, increase vaseular pemeability.VEGF is the central reason that cause microproteinuria during earlier period of DN, and participates in the renal glomerulus selerosis formation with other factors.Objeetive:To observe the therapeutical effect of strenthenin spleeng, supplementing kidney, supplementing qi and nourishing yin on DN rats and discuss the nosogenesis of DM, and then to bring to light about mechanism of action of the traditional Chinese medicine.Methods:The model rats were established with injection STZ and high ealoriediet. Kinds of examination methods were applied, including biochemistry, light microscope, electron microscope, immunohistochemistry, RT-PCR. The invatigated items are: (1) general condition; (2) 24-hoururinaryalbumin(UAlb);(3) Scr,BUN; (4)BW/ RW; (5) the expression of TGFβ1, CTGF, VEGF; (6) the nephridial tissue of pathologieal change and ultrastructural organization.Results: (1)The models of DN rats have been cloned suceessfully; (2) strenthenin spleeng, supplementing kidney, supple- menting qi and nourishing yin, that has good effects on improving general condition and BW/RW, decreasing Scr, BUN,Alb; (3) regulating VEGF; (4) decreasing expression of TGFβ1 mRNA, CTGF mRNA; (5) repairing acinus renis and nephric tubule, improveing hypertransfusion, high percolation, defending renal function.Conclusions: (1) strenthenin spleeng, supplementing kidney, supplementing qi and nourishing yin, that have been determination of treatment based in pathogenesis obtained through differentiation of symptoms and signs of traditional Chinese medicine. It has effective prescription of DN; (2) it has good effects on improving general condition and BW/ RW, decreasing Scr, BUN,Alb, defending renal function, to achieve prevention and cure; (3) restraining the expression of VEGF, TGF-β1 mRNA, CTGFmRNA. To decrease Alb and kidney hypertrophy; (4)repairing acinus renis and nephric tubule, defending renal function. .更多还原