摘要
目的:探讨肾安提取液对链脲佐菌素(STZ)诱导的糖尿病小鼠肾脏转化生长因子-β1(TGF-β1)表达的影响。方法:STZ诱导的糖尿病小鼠模型,随机分为模型组、厄贝沙坦组(厄贝沙坦10mg.kg-1.d-1)、肾安低、中、高剂量组(肾安提取液2.272、4.544、9.088mg.kg-1.d-1),另设正常对照组,疗程4周。检测TGF-β1 mRNA(实时荧光定量PCR法)及蛋白(Western blot分析法)、纤连蛋白(FN)及Smad7蛋白(免疫化学法)表达;透射电镜观察超微结构;并检测血糖、24h尿蛋白定量、肾质量指数、肾小球硬化指数。结果:肾安各组及厄贝沙坦组TGF-β1 mRNA及蛋白表达较模型组明显降低(P<0.01),肾脏FN及Smad7的表达较模型组明显减少(P<0.05,P<0.01);肾脏超微结构改善,肾小球基底膜增厚被明显抑制(P<0.05,P<0.01);24h尿蛋白定量、肾质量指数、肾小球硬化指数均较模型组明显改善(P<0.01);肾安高剂量组及厄贝沙坦组间上述指标无统计学意义;模型组及各药物干预组间血糖差异无统计学意义。结论:肾安提取液可能通过抑制TGF-β1的表达,减轻ECM积聚;并抑制TGF-β1/Smad7信号转导,减少足细胞凋亡,从而对DM肾损害起保护作用。
Objective:To explore the effects of Shen'an extraction on renal tissue transcription transforming growth factor-β1(TGF-β1) expression of diabetic mice.Methods:Diabetic model mice were established by intraperitonesl injection with STZ.All the Diabetic mice randomly divided into model group,irbesartan(10mg·kg-1·d-1) group,Shen'an Extraction low(2.272mg·kg-1·d-1),middle(4.544mg·kg-1·d-1) and high-dose(9.088mg·kg-1·d-1) group.Healthy mice were chosen as healthy control group.After gavage with drugs for 4 weeks,blood glucose,urine protein,kidney weight/body weight(KW/BW) and glomerular sclerosis index were examined.The glomerular super structure was observed by transmission electron microscope.RT-PCR and Western blot methods were applied to detect the mRNA and protein expression of TGF-β1.Fibronectin(FN) and Smad7 were determined by Immunohistochemistry.Results:mRNA and protein expression of TGF-β1 of kidney in each dose group with Shen'an Extraction were significantly lower than model group(P0.01).Compare with model group,FN and Smad7 expression in each dose group with Shen'an Extraction was significantly decreased(P0.05,P0.01).The glomerular super structure was improved,and thickening of glomerular basement membrane(GBM) was relieved.Compare with model group,the level of urine protein,KW/BW and glomerular sclerosis index in each dose group with Shenan Extraction were markedly improved(P0.01).All indexes were no difference between Shen'an high-dose group and irbesartan group.The level of blood glucose was no difference between model group and each dose group with drugs.Conclusion:Shen'an Extraction can delay the diabetic nephropathy events.The mechanism may be related to reduce renal tissue TGF-β1 expression.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2011年第8期1828-1833,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
湖北省自然科学基金资助项目(No.2008CHB414)~~