肾安提取液对糖尿病小鼠肾脏AP-1和TGF-β_1表达的影响

Shen'an Extraction Inhibits the Expression of AP-1 and TGF-β_1 in Renal Tissue of Diabetic Nephropathy Mice

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录激活蛋白-1(AP-1)和转化生长因子-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2.272mg.kg-1.d-1、4.544mg.kg-1.d-1、9.088mg.kg-1.d-1),另设正常对照组,疗程4周。检测肾脏AP-1(western blot分析法)、TGF-β1mRNA(实时荧光定量PCR法)及蛋白(western blot分析法)、纤连蛋白(免疫化学法)表达;并检测血糖、24h尿蛋白定量、血肌酐(Scr)、肾质量指数、肾小球硬化指数。结果:肾安各组及厄贝沙坦组肾脏AP-1和TGF-β1mRNA及蛋白表达较模型组明显降低(P<0.01),肾脏FN的表达较模型组明显减少(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Scr明显降低(P<0.05);肾安高剂量组及厄贝沙坦组间上述指标差异无统计学意义(P>0.05);模型组及各药物干预组间血糖差异无统计学意义(P>0.05)。结论:肾安提取液可延缓糖尿病肾病的发生发展,机制可能与抑制AP-1和TGF-β1的表达有关。

Objective：To explore the effects of Shen＇an extraction on renal tissue transcription activator protein-1（AP-1）and transforming growth factor-β1（TGF-β1）expression of diabetic nephropathy（DN）mice.Methods：DN model mice were established by intraperitonesl injection with STZ.All the DN mice randomly divided into model group,irbesartan（10 mg·kg-1·d-1）group,Shen＇an Extraction low（2.272 mg·kg-1·d-1）,middle（4.544 mg·kg-1·d-1）and high-dose（9.088 mg·kg-1·d-1）group.Healthy mice were chosen as healthy control group.After gavage with drugs for 4 weeks,blood glucose,urine protein,serum creatinine（Scr）,kidney weight/body weight（KW/BW）and glomerular sclerosis index were examined.Western blot method were applied to detect the protein expression of AP-1.RT-PCR and Western blot methods were applied to detect the mRNA and protein expression of TGF-β1.Fibronectin were determined by Immunohistochemistry.Results：Protein expression of AP-1（c-Jun subunit）,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 expression in each dose group with Shen＇an Extraction was significantly decreased（P0.05,P0.01）.Compare with model group,the level of urine protein,KW/BW and glomerular sclerosis index in each dose group with Shen＇an Extraction were markedly improved（P0.01）.The Scr level in Shen＇an Extraction high-dose group were significantly lower than model group（P0.05）.All indexes were no difference between Shen＇an high-dose group and irbesartan group（P0.05）.The level of blood glucose was no difference between model group and each dose group with drugs（P0.05）.Conclusion：Shen＇an Extraction can delay the DN events.The mechanism may be related to reduce renal tissue AP-1 and TGF-β1 expression.