肾气丸通过上调水通道蛋白 1 改善腺嘌呤介导的肾小管周毛细血管损伤
DOI:
作者:
作者单位:

浙江中医药大学药学院,杭州310053,浙江,中国

作者简介:

通讯作者:

中图分类号:

基金项目:


Shen-Qi-Wan Protects the Renal Peritubular Capillary Injury from Adenine-mediated Damage by Upregulating Aquaporin 1
Author:
Affiliation:

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, Zhejiang, China

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    背景:中医认为,“肾主水”,肾气主司和调节全身的水液代谢。肾阳虚者肾的蒸腾气化、固摄、推动等功能受到障碍,影响津液的运化转输,主要表现为腰膝酸软、小便清长、夜尿频多等症状。给予温肾药能很好的改善以上的症状。肾气丸(SQW)为临床上有效的温补肾阳的代表方,主治腰膝酸软、肾虚水肿、肾气不足等。临床上多用于慢性肾炎等慢性肾脏病(Chronic kidney disease, CKD)的患者。在CKD的发生发展过程中,一般均会出现肾小管周围毛细血管损伤的情况。而内皮细胞的血管生成在改善肾脏损伤过程中具有重要意义。水通道蛋白(Aquaporin, AQP)是一种细胞跨膜蛋白,在维持水液代谢平衡方面具有重要意义。在肾损伤后,AQP1介导肾脏血管内皮细胞的迁移,促进血管生成及血管的损伤修复,有利于肾功能恢复。本项目组在前期研究时发现,肾阳虚大鼠肾脏AQP1水平显著降低,而肾气丸能改善肾阳虚大鼠的一般症状体征,提高肾脏AQP1的表达。但肾气丸是否通过促进内皮细胞的血管生成,从而改善肾脏的损伤仍有待研究。目的:观察肾气丸对腺嘌呤所致肾阳虚大鼠肾小管周毛细血管的作用及对人微血管内皮细胞的影响,探讨肾气丸是否通过调控AQP1促人微血管内皮细胞血管生成从而改善肾小管周毛细血管损伤的情况。为指导临床治疗肾虚证及相关疾病,提供新思路。方法:本研究旨在通过体内和体外试验测量 SQW 对管周毛细血管损伤的影响。通过测量下丘脑-垂体-肾上腺(HPA)功能、炎性因子、血管内皮生长因子(VEGF)、CD34(Cluster of differentiation 34)和肾脏AQP1(水通道蛋白1)水平、细胞迁移和管腔形成能力,评估SQW对管周毛细血管损伤的影响。结果:补充SQW可以减轻CKD的病理因素,改善下丘脑-垂体-肾上腺(HPA)轴功能障碍和腺嘌呤引起的肾功能丧失。SQW 还显著抑制炎症细胞因子,包括 MCP-1 和 VCAM-1 水平。同时,SQW 可以改善腺嘌呤诱导的肾脏毒性,并通过增加 AQP1 mRNA 和蛋白质水平减轻腺嘌呤引起的肾小管周围毛细血管的损伤。在体外实验中,SQW含药血清增强了HMEC-1细胞的迁移和管腔形成能力,并显著提高了AQP1蛋白水平。此外,AQP1 敲低有效抑制了 HMEC-1 细胞的迁移和管腔形成能力,这种作用可以通过 SQW 含药血清逆转。结论:这些结果表明,SQW通过促进内皮细胞的血管生成来减轻腺嘌呤诱导的CKD模型大鼠肾小管周围毛细血管损伤,AQP1可能是SQW治疗肾损伤的潜在靶点。

    Abstract:

    Background: Shen-Qi-Wan (SQW), a commonly used prescription against chronic kidney disease (CKD) in Traditional Chinese Medicine (TCM), has a nephroprotective action in adenine-induced kidney injury. However, the mechanism of SQW in renal injury remains unclear.Objective: This study was undertaken to measure the effect of SQW on peritubular capillary injury both in vivo and in vitro assays.Methods: The effect of SQW on the peritubular capillary injury was evaluated according to measuring hypothalamic-pituitary-adrenal (HPA) function, inflammatory cytokines, VEGF (vascular endothelial growth factor), CD34 (Cluster of differentiation 34), and AQP1 (Aquaporin 1) levels in the kidney, cell migration, and lumen forming capacity.Results: SQW supplementation could ameliorate dysfunction of the HPA and renal function loss induced by adenine. SQW also significantly inhibited the inflammatory cytokines including MCP-1 (monocyte chemotactic protein-1) and VCAM-1 (vascular cell adhesion molecule-1) level. Alternatively, SQW administration showed an ameliorating effect from the toxicity and alleviated the injury of capillaries around renal tubules instigated by adenine through increasing AQP1 mRNA and protein level. SQW medicated the serum enhanced the migration and lumen formation ability of HMEC-1 cells, and significantly increased AQP1 protein level. Moreover, AQP1 knockdown efficiently inhibited the migration and lumen formation ability in HMEC-1 cells, and weakened the effect of SQW medicated serum. Conclusion: These results suggested that SQW attenuated peritubular capillary injury in adenine-induced CKD model rats through boosting angiogenesis in endothelial cell, and AQP1 may be a potential target of SQW for treating the renal injury.

    参考文献
    相似文献
    引证文献
引用本文
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2021-11-08
  • 出版日期: