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作 者:李志杰[1] 张悦[1] 刘煜敏[1] 陆海英[1] 李亚丽[1] 张燕[1]
机构地区:[1]上海中医药大学,上海201203
出 处:《中华中医药学刊》2011年第8期1728-1731,I0001,共5页Chinese Archives of Traditional Chinese Medicine
基 金:国家自然科学基金资助项目(30371834);上海市教育委员会重点学科(第5期)项目(J50301);上海高校创新团队建设项目;上海市高校优秀青年教师专项基金资助项目
摘 要:目的:观察足细胞裂孔隔膜蛋白nephrin和podocin在糖尿病肾病发病机制中的作用,探讨六味地黄丸(LWDHW)保护糖尿病肾病大鼠肾脏的机制。方法:SD大鼠腹腔注射链脲佐菌素复制糖尿病模型,1周后,按血糖浓度将成模的糖尿病大鼠随机分为:模型组(STZ,8只)、治疗组(STZ+LWDHW,8只),另设正常组(Control,8只)。治疗组给予六味地黄丸灌胃,模型组、正常组给予等量生理盐水,持续观察8周。治疗第8周末,称大鼠体重,计算肾系数,观察肾脏病理改变;检测24h尿蛋白总量、血尿素氮、血肌酐;免疫印迹检测nephrin和podocin在肾组织中的表达。结果:与正常组比较,模型组大鼠血糖,体重明显下降(P<0.01),肾系数,24h尿蛋白总量,血尿素氮,血肌酐明显升高(P<0.01);模型组大鼠肾小球肥大、毛细血管基底膜增厚,系膜基质增生,肾小管上皮细胞空泡样变,见蛋白管型;nephrin和podocin蛋白表达减少(P<0.01)。治疗组血糖、体重无明显改变;肾系数,24h尿蛋白总量,血尿素氮,血肌酐明显降低(P<0.05);病理改变明显减轻;大鼠肾组织nephrin和podocin表达明显增加(P<0.05)。结论:六味地黄丸可能通过增加足细胞nephrin和podocin表达发挥保护糖尿病肾病大鼠肾脏的作用。Objcetivt: To investigate the role of the nephrin and podocin in podocytes slit diaphragm in diabetic nephropathy(DN) pathogenesis and study the mechanism of prevention and treatment this disease the effects of Liu Wei Di Huang Wan.Methods:The rat model of diabetes was induced by intraperitoneal injection of Streptozotocin(STZ),and diabetic rats were randomly divided into 2 groups by blood glucose concentration: STZ group(n=8) and LWDHW group(n=8).In addition,8 non-treated rats served as control group.All the rats were received daily gavage respectively for 8 weeks.8 weeks later,body weight and renal index were measured;total urinary protein in 24 h,blood urea nitrogen(BUN),serum creatinine(SCr) were detected with correlative methods and the pathological changes of kidney were also observed under light microscope.The nephrin and podocin protein in kidney tissue were also determined by Western blotting.Results:In DN rats,the levels of renal index,blood glucose concentration,total urinary protein in 24h,BUN,SCr were significantly higher and body weight lower than those in the control group(P0.01).Pathological examination of kidney in the DN group showed glomerular hypertrophy;glomerular basement membrane thickening;tubular epithelial cell degeneration;mesangial matrix proliferation;protein cast formation in some renal tubules.The protein expression levels of nephrin and podocin were markedly decreased(P0.01).After LWDHW intervention,the level of renal index,total urinary protein in 24 h,BUN,SCr were significantly lower and body weight was higher than those in the DN group(P0.05).The renal histological injury in treatment group was significantly ameliorated and the expression of nephrin and podocin at the protein level were upregulated markedly than those in the DN group(P0.05).Conclusion:LWDHW might protect kidney against STZ-induced injury via increasing the expression of nephrin and podocin in podocytes.
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