...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Clinical and experimental pharmacology & physiology >Chronic treatment with tempol does not significantly ameliorate renal tissue hypoxia or disease progression in a rodent model of polycystic kidney disease
【24h】

Chronic treatment with tempol does not significantly ameliorate renal tissue hypoxia or disease progression in a rodent model of polycystic kidney disease

机译：在多囊性肾脏疾病的啮齿动物模型中，用tempol进行的慢性治疗不能明显改善肾脏组织的缺氧或疾病进展

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Summary: In the present study, we tested whether polycystic kidney disease (PKD) is associated with renal tissue hypoxia and oxidative stress, which, in turn, contribute to the progression of cystic disease and hypertension. Lewis polycystic kidney (LPK) rats and Lewis control (Lewis) rats were treated with tempol (1 mmol/L in drinking water) from 3 to 13 weeks of age or remained untreated. The LPK rats developed polyuria, uraemia and proteinuria. At 13 weeks of age, LPK rats had greater mean arterial pressure (1.5-fold), kidney weight (sixfold) and plasma creatinine (3.5-fold) than Lewis rats. Kidneys from LPK rats were cystic and fibrotic. Renal hypoxia was evidenced by staining for pimonidazole adducts and hypoxia-inducible factor (HIF)-1α in cells lining renal cysts and upregulation of HIF-1α and its downstream targets vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1) and heme oxygenase 1 (HO-1). However, total HO activity did not differ greatly between kidney tissue from LPK compared with Lewis rats. Renal oxidative and/or nitrosative stress was evidenced by ninefold greater immunofluorescence for 3-nitrotyrosine in kidney tissue from LPK compared with Lewis rats and a > 10-fold upregulation of mRNA for p47phox and gp91phox. Total renal superoxide dismutase (SOD) activity was sevenfold less and expression of SOD1 mRNA was 70% less in kidney tissue from LPK compared with Lewis rats. In LPK rats, tempol treatment reduced immunofluorescence for 3-nitrotyrosine and HIF1A mRNA while upregulating VEGF and p47phox mRNA expression, but otherwise had little impact on disease progression, renal tissue hypoxia or hypertension. Our findings do not support the hypothesis that oxidative stress drives hypoxia and disease progression in PKD.
机译：摘要：在本研究中，我们测试了多囊性肾脏疾病（PKD）是否与肾脏组织缺氧和氧化应激有关，而肾脏组织缺氧和氧化应激又导致了囊性疾病和高血压的发展。 Lewis多囊肾（LPK）大鼠和Lewis对照（Lewis）大鼠在3至13周龄时用tempol（饮用水中1 mmol / L）治疗或未治疗。 LPK大鼠发展为多尿，尿毒症和蛋白尿。与Lewis大鼠相比，LPK大鼠在13周龄时的平均动脉压（1.5倍），肾脏重量（6倍）和血浆肌酐（3.5倍）更高。 LPK大鼠的肾脏呈囊性和纤维化。肾脏缺氧可通过在肾脏囊肿内衬细胞中的吡莫尼唑加合物和缺氧诱导因子（HIF）-1α染色以及HIF-1α及其下游靶标血管内皮生长因子（VEGF），葡萄糖转运蛋白1（Glut-1）的上调来证明）和血红素加氧酶1（HO-1）。但是，与Lewis大鼠相比，LPK肾脏组织之间的总HO活性差异不大。与Lewis鼠相比，LPK肾脏组织中3-硝基酪氨酸的免疫荧光增强了9倍，而p47phox和gp91phox的mRNA上调了10倍以上，从而证明了肾脏的氧化和/或亚硝化应激。与Lewis大鼠相比，LPK肾脏组织中的总肾脏超氧化物歧化酶（SOD）活性降低了7倍，SOD1 mRNA的表达降低了70％。在LPK大鼠中，用tempol处理可降低3-硝基酪氨酸和HIF1A mRNA的免疫荧光，同时上调VEGF和p47phox mRNA的表达，但对疾病进展，肾脏组织缺氧或高血压影响不大。我们的发现不支持氧化应激导致PKD缺氧和疾病进展的假说。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号