六味地黄汤对慢性肾衰大鼠肾组织中HIF-1α和PAI-1表达的影响

Effects of six ingredient rehmannia decoction on expression of HIF-1 αand PAI-1 in chronic renal failure rats

目的探讨六味地黄汤抗肾间质纤维化的作用机制。方法 5/6肾切除法制备慢性肾衰模型,分假手术组、模型组、六味地黄汤组和依那普利组。六味地黄汤组予以6.25 g/(kg·d)六味地黄汤灌胃,依那普利组予以10 mg/(kg·d)依那普利灌胃,假手术组和模型组予以10 m L/(kg·d)蒸馏水灌胃,每天1次,连续灌胃12周。造模12周后,应用免疫组化法和RT-PCR法分别检测HIF-1α、PAI-1在肾组织中蛋白水平和基因表达。结果与假手术组比较,模型组大鼠肾组织中HIF-1α、PAI-1蛋白水平和基因表达均明显升高(P<0.05);与模型组比较,六味地黄汤组和依那普利组大鼠肾组织中HIF-1α、PAI-1蛋白水平和基因表达均明显降低(P<0.05),且六味地黄汤组低于依那普利组(P<0.05)。结论六味地黄汤可能通过降低HIF-1α,进而下调PAI-1的表达抑制肾间质纤维化,且治疗效果优于依那普利。

Objective To investigate the mechanism of six ingredient rehmannia decoction against renal interstitial fibrosis. Methods The rat model of renal interstitial fibrosis were induced by 5/6 nephrectomy, rats were divided into sham operation group, model group, six ingredient rehmannia decoction group and enalapril group. Six ingredient rehmannia decoction group was given 6.25 g/（kg· d） of six ingredient rehmannia decoction gavage, enalapril group was given 10 mg/（kg·d） enalapril lavage, sham operation group and model group were given 10 mL/（kg· d） of distilled water, 1 times a day, continuous intragastric administration for 12 weeks. 12 weeks after modeling, immunohistochemical method and RT-PCR method were used to detect protein levels and gene expression of HIF-lct and PAI-1 in renal tissue respectively. Results Compared with the sham operation group, the renal tissue of HIF-1 ot, PAI-1 protein level and gene expression were increased significantly in model group （P〈0.05）; Compared with the model group, the renal tissue of HIF-1 α, PAI-1 protein levels and gene expression were decreased significantly in six ingredient rehmannia decoction group and enalapril group（P〈0.05）, and the six ingredient rehmannia decoction group was better than that of enalapril group（P〈0.05）. Conclusion Six ingredient rehmannia decoction can decrease the HIF-1 α, and down regulate the expression of PAI-1 inhibits renal interstitial fibrosis, and the treatment effect is better than that of enalapril.