六味地黄汤对肾间质纤维化大鼠肾组织中缺氧诱导因子-1α和Ⅰ、Ⅲ型胶原表达的影响

Effects of Liuwei Dihuang Decoction on Expressions of HIF-1α, CollⅠ, and CollⅢ in Renal Interstitial Fibrosis Rats

目的探讨六味地黄汤抗肾间质纤维化的作用机制。方法采用5/6肾切除法复制肾间质纤维化大鼠模型,随机分为假手术组、模型组、六味地黄汤组和依那普利组。六味地黄汤组予6.25 g/(kg·d)六味地黄汤灌胃,依那普利组予10 mg/(kg·d)马来酸依那普利悬浊液灌胃,假手术组和模型组予10 m L/(kg·d)蒸馏水灌胃,每日1次,连续12周。采用免疫组化法检测缺氧诱导因子-1α(HIF-1α)和Ⅰ、Ⅲ型胶原(CollⅠ、CollⅢ)在肾组织中的表达。结果与假手术组比较,模型组肾组织中HIF-1α、CollⅠ、CollⅢ的表达均明显升高(P<0.05);与模型组比较,六味地黄汤组和依那普利组肾组织中HIF-1α和CollⅠ、CollⅢ的表达均降低(P<0.05),且六味地黄汤组优于依那普利组(P<0.05)。结论六味地黄汤可能通过下调HIF-1α和CollⅠ、CollⅢ的表达,改善肾组织慢性缺氧,发挥抗肾间质纤维化的作用。

Objective To discuss the mechanism of Liuwei Dihuang Decoction against renal interstitial fibrosis. Methods The rat models of renal interstitial fibrosis were induced by 5/6 nephrectomy, and were randomly divided into sham-operation group, model group, Liuwei Dihuang Decoction group and enalapril group. Liuwei Dihuang Decoction group was given 6.25 g/（kg-d） of Liuwei Dihuang Decoction for gavage, enalapril group was given 10 mg/（kg-d） enalapril for gavage, sham-operation group and model group were given 10 mL/（kg-d） of distilled water for gavage, 1 time per day for 12 weeks. Expressions of HIF-1α, CollI, and CollIII in kidney tissue were detected by immunohistochemistry. Results Compared with the sham-operation group, the expressions of HIF-1α, CollI, and CollIII of renal tissue in the model group significantly increased （P〈0.05）. Compared with the model group, Liuwei Dihuang Decoction group and enalapril group can inhibit the expressions of HIF-1α, CollI, and CollIII （P〈0.05）, and Liuwei Dihuang Decoction group was better than enalapril group （P〈0.05）. Conclusion The mechanism of Liuwei Dihuang Decoction against renal interstitial fibrosis may improve the renal tissue of chronic hypoxia to play the role of preventing renal interstitial fibrosis by decreasing the expressions of HIF-1α, CollI, and CollIII.