化瘀通络中药对糖尿病肾病大鼠肾脏足细胞密度的干预作用

Intervention of Chinese herbs for stasis removing and collaterals dredging on podocyte density in the diabetic nephropathy rats

关键词:  糖尿病肾病  化瘀通络中药  蛋白尿  整合素α3β1

Key words:  diabetic nephropathy  Chinese herbs for stasis removing and collaterals dredging  proteinuria  integrin α3β1

摘要:

[目的] 分析化瘀通络中药对糖尿病肾病（DN）大肾脏整合素α3β1表达及足细胞密度的影响。[方法] 糖尿病大鼠模型采用高脂饲料联合腹腔注射链脲佐菌素建立，大鼠分为正常组、模型组、厄贝沙坦组和中药组，各组相应药物剂量灌胃。灌胃20周后检测各组大鼠空腹血糖（FBG）、血肌酐（Scr）、尿素氮（BUN）、24h尿蛋白定量（24h UTP），肾组织行光镜观察，分别采用实时聚合酶链反应（RT-PCR）及免疫组化（IHC）检测肾脏整合素α3（ITGA3）、整合素β1（ITGB1）、WT1 mRNA及蛋白的表达，计算足细胞密度。[结果] 与正常组比较，模型组各项指标差异均有统计学意义（P＜0.05）；与模型组比较，两治疗组BUN、24hUTP明显下降（P＜0.05），ITGA3、ITGB1、WT1 mRNA表达水平及足细胞密度明显上升（P＜0.05），干预组病理损伤明显减轻，主要表现为肾小球内细胞基质及系膜细胞明显减少；与厄贝沙坦组比较，中药组24h UTP明显降低（P＜0.05），ITGB1 mRNA及足细胞密度明显上升。[结论] 化瘀通络中药对糖尿病肾病大鼠肾脏有保护作用，其机制可能与调节整合素α3β1表达从而减少足细胞脱落相关。

Abstract:

[Objective] To discuss the effect of Chinese herbs for stasis removing and collaterals dredging upon the the expression of renal integrin α3β1 and podocyte density in the renal of diabetic nephropathy rats. [Methods] The diabetes rat model was induced by feeding high-glucose high-fat diet combination with intraperitoneal injection of STZ. Rats were divided into normal group,model group,Chinese medicine group,and irbesartan group,all groups were given relevant medicinal intragastrically. Lavage for 20 weeks,detected rats' fasting blood glucose (FBG),serum creatinine (Scr),urea nitrogen (BUN),24h urinary protein quantitative (24h UTP). Renal tissue was examined by light microscopy. The expression of renal ITGA3,ITGB1,WT1 mRNA and protein were determined by Real-time PCR and immunohistochemistry,and podocyte density was calculated. [Results] Compared with normal group,there were differences between the model group(P<0.05). Two treatment groups compared with model group,BUN and 24h UTP significantly reduced(P<0.05),ITGA3, ITGB1,WT1 mRNA expression and podocyte density increased significantly (P<0.05). The pathological damage was significantly reduced in the intervention group,mainly manifested by the obvious decrease of cellular matrix and mesangial cells in the glomerulus. Compared with irbesartan group,Chinese medicine group of 24h UTP decreased obviously (P<0.05),ITGB1 mRNA expression and podocyte density increased significantly (P<0.05). [Conclusion] Chinese Herbs for stasis removing and collaterals dredging has a protective effect on the kidney of diabetic nephropathy rats and its mechanism may be associated with regulation of integrin α3β1 expression and thereby reducing podocyte shedding.