基于蛋白质组学分析奈比洛尔改善UUO大鼠肾间质纤维化

Amelioration of nebivolol on renal interstitial fibrosis in UUO rats based on proteomic analysis

目的:观察奈比洛尔改善单侧输尿管梗阻(UUO)大鼠肾间质纤维化(RIF)的作用,并利用蛋白质组学探讨其机制。方法:SD大鼠分为:Sham组;UUO组;Neb组(UUO大鼠给予奈比洛尔10 mg·kg^(-1)·d^(-1),i.g.)。各组分别在造模7 d,14 d和21 d时,麻醉大鼠,分离左侧梗阻肾。HE染色观察肾脏结构,Masson染色测RIF程度。利用蛋白质组学筛选造模21 d,UUO/Sham和Neb/UUO之间共有,且奈比洛尔回调差异蛋白,进行生物信息学分析。Western blot验证关键蛋白表达。结果:与Sham组比较,UUO大鼠RIF呈渐进性加重。奈比洛尔给药21 d显著改善UUO大鼠左肾RIF。与UUO/Sham比较,奈比洛尔回调差异蛋白179个。KEGG富集分析和PPI网络显示,回调差异蛋白主要涉及剪接体通路。Western blot证实Rbm8a、Srsf9、Sart1蛋白表达与蛋白组学结果一致。结论:奈比洛尔改善UUO大鼠肾间质纤维化可能与调节剪接体密切相关。

AIM:To explore the effect and mechanism of nebivolol on renal interstitial fibrosis(RIF) in unilateral ureteral obstruction(UUO) model through TMT proteomics.METHODS:SD rats were divided into Sham group,UUO group,Neb group(UUO rats treated with nebivolol 10 mg·kg^(-1)·d^(-1),i.g.).Left kidney was collected from rat on 7 th,14 th and 21 th day after modeling.HE staining was used to observe renal structure and Masson’s staining was used to examine RIF.Proteomic and bioinformatics were conducted to screen and analysis the differential expressed proteins contrary regulated between UUO/Sham and Neb/UUO 21 d after obstruction.Western blot were used to confirm protein expressions.RESULTS:Compared with Sham group,RIF in UUO rats aggravated gradually.Administration of nebivolol for 21 d ameliorated RIF in UUO rats.A total of 179 differential expressed proteins contrary regulated were identified shared between UUO/Sham and Neb/UUO groups.KEGG enrichment analysis and PPI showed that these differential expressed proteins were mainly involved in spliceosome pathway.Results of Western blot for Rbm8 a,Srsf9 and Sart1 were in line with the results of proteomics.CONCLUSION:Spliceosome may play key role in the amelioration of nebivolol on RIF in UUO rats.