肾衰保肾胶囊改善腺嘌呤诱导大鼠肾间质纤维化的机制初探

Protecting Mechanism of Shenshuai Baoshen Capasule on Renal Interstitial Fibroblast Induced by Adenine in Rats

摘要:

目的: 研究拟从肾衰保肾胶囊对慢性肾间质纤维化大鼠细胞外基质积聚的影响的角度探讨肾衰保肾胶囊保护肾功能的机制。 方法: Wistar大鼠60只随机分为空白对照组、模型对照组、肾衰保肾胶囊低剂量组(0.324 g ·kg^-1 ·d^-1)和肾衰保肾胶囊高剂量组(1.296 g ·kg^-1 ·d^-1),采用腺嘌呤ig复制慢性肾间质纤维化大鼠模型,各组分别给药8周,检测大鼠肾功能、病理变化,采用免疫组化法检测肾组织中的I型胶原(ColⅠ)、基质金属蛋白酶1(MMP-1)、金属蛋白酶组织抑制物1(TIMP-1)及纤溶酶原激活物抑制物1(PAI-1)的表达。 结果: 肾衰保肾胶囊能够改善模型大鼠肾脏纤维化程度,降低血肌酐(Scr)、血尿素氮(BUN)、血尿酸(UA)水平,降低肾组织中的ColⅠ, TIMP-1及PAI-1蛋白表达,升高MMP-1蛋白表达,与模型组比较有显著性差异(P<0.01,P<0.05)。 结论: 肾衰保肾胶囊可能是通过增加MMP-1表达及减少TIMP-1, PAI-1的表达来减少模型大鼠肾组织中I胶原的积聚,进而发挥减轻肾间质纤维化保护肾功能的作用。

Abstract:

Objective: To investigate the effects of the Shenshuai Baoshen Capsule on extracellular matrix accumulation in rat renal interstitial fibroblast, and analyze the mechanisms of the kidney protection effects of the Shenshuai Baoshen Capsule. Method: Sixty Wistar rats were randomly divided into blank control group, model control group, Shenshuai Baoshen capsule low dose group and high dose group. The model was established by ig administration of adenine. Different groups were treated for 8 weeks,The pathlological changes in kidney functions after therapy were observed. The protein collagen Ⅰ, MMP-1(matrix metalloproteinase-1), TIMP-1(tissue inhibitor of metalloproteinase-1), PAI-1(plasminogen activator inhibitor) expression in kidney tissue were detected respectively by immunohistochemistry. Result: The pathlological changes were reduced in Shenshuai Baoshen capsule group, Cr, BUN and UA were reduced, the expression of collagen Ⅰ, TIMP-1,PAI-1 protein in kidney tissue were reduced, and the expression of MMP-1 was induced which had the significant difference compared with that in the model group(P<0.01,P<0.05). Conclusion: The Shenshuai Baoshen Capsule could depress the collagen Ⅰprotein accumulation in renal tissue, by rising MMP-1 expression, depressing TIMP-1,PAI-1 protein expression. Therefore, the renal interstitial fibroblast was relieving by Shenshuai Baoshen Capsule, and chronic renal failure progress was delayed.