还原型谷胱甘肽对单侧输尿管梗阻致肾间质纤维化的保护作用

Protective effects of reduced glutathione on renal interstitial fibrosis induced by unilateral ureteral obstruction

目的采用单侧输尿管梗阻（UUO）致肾间质纤维化大鼠模型，观察还原型谷胱甘肽（GSH）对转化生长因子β激活激酶（TAK1）表达的影响及对肾间质纤维化的保护作用。方法将72只大鼠随机分为假手术组、UUO模型组和GSH治疗组（GSH组）3组，每组24只。GSH组于术前1天给予还原型谷胱甘肽每天200mg／kg，腹腔注射。假手术组与UUO模型组给予等量生理盐水腹腔注射。HE及Masson染色观察梗阻侧肾脏病理变化，原位杂交及实时荧光定量PCR（RT—PCR）检测肾组织TAK1 mRNA的表达，Western—bloting检测TAK1及α-平滑肌肌动蛋白（α—SMA）的表达。结果与假手术组比较，UUO模型组TAK1及α—SMA的表达在UUO术后7天显著增加（P〈0．05），但UUO模型组显著高于GSH组（P〈0．05）。结论GSH可能通过下调TAK1及α-SMA的表达，从而减轻UUO致肾间质纤维化的进展。

Objective To investigate the effect of reduced glutathione （GSH）on expression of TGFβ-activated kinase 1 （ TAK1 ） and renal interstitial fibrosisinduced by unilateral ureteral obstruction （UUO） in rat kidney. Methods A total of 72 male Sprague-Wistar rats were randomly divided into three groups ： sham-operated group （ n = 24）, UUO model group （ n = 24） and reduced glutathione treatment group （GSH group）（ n = 24）. The rats received 200 mg/（ kg · d）reduced glutathione by gastric gavage in the GSH group from 1 d before the operation, and the rats received the identical dose of normal saline in the other two groups. The renal pathological changes were observed by HE and Masson staining, the mRNA expression of TAK1 was detected by In situ hybridization and real-time PCR, and the protein expression of TAK1 and α-SMA were detected by Western bloting. Results TAK1 and α-SMA expression gradually increased from 7 day in model group, and was significant higher than sham-operated group（ P 〈 0.05 ）, compared with UUO group, reduced glutathione could significantly decreased the expression of TAK1 and α- SMA （P 〈 0.05）. Conclusion Reduced glutathione may play a protective role in the kidney by downregalating the expression of TAK1 and α-SMA, and it can alleviate the development of renal interstitial fibrosis induced by UUO.