复肾颗粒对肾间质纤维化大鼠肾脏的保护作用

Protective Effect of Fushen Granule on Renal Tubulointerstitial Fibrosis in Rat

目的:观察复肾颗粒在肾间质纤维化过程中对转化生长因子β激活激酶(TAK1)表达的影响及其可能的肾脏保护作用机制。方法:采用单侧输尿管结扎(UUO)致肾间质纤维化大鼠模型,将60只大鼠随机分为6组:假手术组(N)、模型组(M,UUO组)、福辛普利组[F0,10 mg.kg-1.d-1]、复肾颗粒1组(F1,7.5 g.kg-1.d-1)、复肾颗粒2组(F2,15 g.kg-1.d-1)、复肾颗粒3组(F3,30 g.kg-1.d-1)。14 d后处死大鼠,取结扎侧肾组织采用HE及Masson染色观察病理变化,RT-PCR和Western-bloting检测肾组织TAK1和α-SMA的表达。结果:模型组大鼠肾纤维化程度及肾组织TAK1和α平滑肌肌动蛋白(α-SMA)的表达较假手术组显著升高(P<0.01),复肾颗粒各组及福辛普利组较模型组显著降低,尤以复肾颗粒2组为甚(P<0.01,P<0.05)。结论:复肾颗粒可能通过降低TAK1和α-SMA的含量而起到减轻肾间质纤维化病程进展的作用,推测其抑制TAK1和α-SMA表达上调的作用可能是其抗肾小管间质纤维化的机制之一。

Objective：To observe the effects of Fushen Granule on the expression of TAK1 and during renal interstitial fibrosis in rat and explore the possible mechanism.Method：Rat model of renal interstitial fibrosis was produced by unilateral ureter obstruction（UUO）.60 Sprague-Wistar male rats were randomly divided into six groups：sham group（N）,UUO model group（M）,fosinopril group（F0,10 mg·kg^-1·d^-1）,Fushen Granule group 1（F1,7.5 g·kg^-1·d^-1）,Fushen Granule group 2（F2,15 g·kg^-1·d^-1） and Fushen Granule group 3（F3,30 g·kg^-1·d^-1）.All the rats were sacrificed at 14 days after UUO.It was carried out to measure the level of tubulointerstitial damage by HE and Masson staining.The mRNA and protein expression of TAK1 and α-SMA was detected by real-time PCR and Western blot.Result：The renal interstitial fibrotic area and the expression of TAK1 and α-SMA in M group were significantly higher than that in the sham group（P 〈0.01）.In comparison with M group,each intervention group with Fushen Granule or with fosinopril could markedly decreased the expression of TAK1 and α-SMA,especially in Fushen Granule group 2（P〈 0.01 or P〈 0.05）.Conclusion：Fushen Granule may downregulate the levels of TAK1 and decrease renal interstitial fibrosis.It is inferred that it may be one of the mechanisms for Fushen Granule to suppress renal tubular damage and interstitial fibrosis.