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Involvement of spliced X-box binding protein 1 in renal fibrosis induced by unilateral ureteral obstruction in mice

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Author:
No author available
Journal Title:
Acta Physiologica Sinica
Issue:
2
DOI:
10.13294/j.aps.2016.0020
Key Word:
内质网应激;肾纤维化;剪切型X盒结合蛋白1;氧化应激;endoplasmic reticulum stress;fibrosis;spliced X-box binding protein 1;oxidative stress

Abstract: 剪切型X盒结合蛋白1 (spliced X-box binding protein 1,XBP1S)是内质网应激关键信号分子.有研究表明XBPlS在肾脏系膜细胞具有抗氧化应激和抗凋亡作用,而氧化应激是肾纤维化发生发展重要因素.缬沙坦(valsartan)具有改善肾纤维化作用.本研究旨在探讨valsartan能否通过XBP1S进而影响肾间质纤维化发展.C57BL/6J小鼠行左侧输尿管结扎(unilateral ureteral obstruction,UUO)制作肾纤维化模型,valsartan组于造模前1d起每天给予valsartan (20 mg/kg)灌胃,UUO组和对照组给予等容积生理盐水灌胃,于手术后第7天处死动物,取左侧肾.HE、Masson和天狼星红(Sirius red)染色观察肾间质纤维化;免疫组化染色观察XBP1S在肾间质表达;Western blot检测XBP1S、纤维连接蛋白(fibronectin)、α-平滑肌肌动蛋白(α-smooth muscle actin,a-SMA)、BAX和BCL2蛋白水平;实时荧光定量PCR检测NADPH氧化酶亚基p47-phox与p67-phox mRNA水平.结果显示,与对照组相比,UUO组XBP1S蛋白水平明显降低,valsartan明显升高UUO小鼠XBP1S蛋白水平;HE、Masson和Sirius red染色结果显示valsartan明显改善UUO小鼠肾间质纤维化;Western blot结果显示valsartan明显降低UUO小鼠fibronectin、BAX/BCL2、a-SMA蛋白水平.实时荧光定量PCR结果显示:UUO组p47-phox与p67-phoxmRNA水平明显较对照组升高,相比较于UUO组,valsartan明显降低UUO小鼠p47-phox与p67-phox mRNA水平.以上结果提示,XBP1S蛋白水平下调与UUO模型的肾间质纤维化有关,其机制可能与XBP1S抗氧化应激相关.

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