基础医学与临床 ›› 2018, Vol. 38 ›› Issue (3): 361-369.

• 研究论文 • 上一篇    下一篇

硒与苯那普利抑制单侧输尿管梗阻大鼠肾间质纤维化

徐刚,邹循亮,傅珍春,鄢巨振,张夏明,尹洪萍,亢晓冬   

  1. 杭州师范大学附属医院
  • 收稿日期:2017-02-06 修回日期:2017-05-24 出版日期:2018-03-05 发布日期:2018-02-27
  • 通讯作者: 徐刚 E-mail:xugang58@Aliyun.com
  • 基金资助:
    杭州市科技计划发展项目

Selenium and benazepril inhibit renal interstitial fibrosis in rat with unilateral ureteral obstruction

  • Received:2017-02-06 Revised:2017-05-24 Online:2018-03-05 Published:2018-02-27
  • Contact: Gang XU E-mail:xugang58@Aliyun.com

摘要: 目的 研究亚硒酸钠与苯那普利对单侧输尿管梗阻(UUO)大鼠肾间质纤维化(RIF)的保护作用及其机制。方法 将大鼠随机分为假手术组、UUO组(结扎单侧输尿管建立UUO模型)、UUO+硒组(亚硒酸钠0.2 mg/kg?d灌胃)和UUO+苯那普利组(苯那普利10 mg/kg?d灌胃),每组18只。术后第7、14和21天各组随机处死6只大鼠,肾组织行HE和Masson染色,观察RIF程度;免疫组化法检测结缔组织生长因子(CTGF)、转化生长因子-β1(TGF-β1)、α- 平滑肌肌动蛋白(α-SMA)和Ⅲ型胶原(Col Ⅲ)的表达;Western blot检测CTGF和TGF-β1蛋白表达;比色法检测谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)和丙二醛(MDA)的含量。结果 术后第7、14和21天,硒组和苯那普利组RIF较UUO组明显减轻(P < 0.05 );肾组织CTGF、TGF-β1、α-SMA、Col Ⅲ表达强度和MDA含量明显低于UUO组(P < 0.01 或P < 0.05);GSH-Px和SOD含量明显高于UUO组(P < 0.05)。两干预组之间各项指标无明显差异。UUO组TGF-β1、CTGF、 a-SMA、ColⅢ的表达和RIF指数与MDA含量呈正相关(P < 0.05),与SOD和GSH-Px含量呈负相关(P < 0.05);CTGF与a-SMA、ColⅢ的表达呈正相关(P < 0.05),CTGF、a-SMA和ColⅢ表达与RIF病变程度呈正相关(P < 0.05)。 结论 亚硒酸钠与苯那普利均可减轻UUO模型大鼠RIF。

关键词: 硒, 苯那普利, 单侧输尿管梗阻, 肾间质纤维化

Abstract: Objective To compare and study the protective effect of the sodium selenite and benazepril on renal interstitial fibrosis(RIF) in rat model of unilateral ureteral obstruction(UUO) and its mechanism . Methods The male SD of clean grade rats were randomly divided into sham-operation group, UUO group (UUO model was established by ligating unilateral ureter), UUO+ sodium selenite group group(sodium selenite 0.2mg/kg?d gavage), UUO+ benazepril group (benazepril 10mg/kg?d gavage), with 18 in each group.At day 7,14 and 21 after the treatment, 6 rats selected randomly from each group were killed.The extent of RIF was evaluated by HE and Masson staining of the renal tissue. The expression of connective tissue growth factor(CTGF),transforming growth factor-β1(TGF-β1),alpha smooth muscle actin(α-SMA) and III collagen( Col III ) were detected by Immunohistochemical method.The protein expression of CTGF and TGF-β1 were detected by western blotting. Chemical colorimetric method was used to detected the contents of supper oxide dismutase (SOD) ,malondialdehyde (MDA) and glutathione peroxidase ( GSH -px) in renal cortex. Results The extent of RIF and the expression of CTGF,TGF-β1, α-SMA and Col III in renal cortex were significantly lower in sodium selenite group and benazepril group at day 7,14 and 21 after the operation compared with that in UUO group(P<0.05 or P<0.01 ). In sodium selenite group and benazepril group ,the contents of SOD and GSH -px in renal cortex were higher significantly than those in UUO group at day 7,14 and 21 after the operation respectively(P<0.05),but the MDA in renal cortex was significantly decreased(P﹤0.05).There were no significant differences in the indexes between the two groups of sodium selenite and benazepril. The expression of CTGF,TGF-β1, α-SMA ,Col III and the extent of RIF were positively correlated to the level of MDA in UUO group (P ﹤0.05,respectively), and negatively correlated to the level of SOD and GSH-Px(P ﹤0.05,respectively). The expression of CTGF was positively correlated to the expression of α-SMA and Col III in UUO group(P <0.05).The expression of CTGF、a-SMA and ColⅢ were positively correlated to RIF in UUO group (P <0.05). Conclusions Sodium selenite and benazepril can reduce the extent of RIF in rat model with unilateral ureteral obstruction.

Key words: Selenium, benazepril, unilateral ureteral obstruction, renal interstitial fibrosis

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