解剖学报

解剖学报 ›› 2021, Vol. 52 ›› Issue (4): 621-627.doi: 10.16098/j.issn.0529-1356.2021.04.018

• 组织学胚胎学发育生物学 • 上一篇    下一篇

黄芪甲苷通过toll样受体4/核因子κB通路介导辐射所致肾损伤的防护作用

徐郁琴1 丁艳平1* 刘淑宁1 康洁1 邵宝平2   

  1. 1.西北师范大学生命科学学院， 兰州 730070;  2.兰州大学生命科学学院， 兰州 730000
  • 收稿日期:2020-01-09 修回日期:2020-07-07 出版日期:2021-08-06 发布日期:2021-08-06
  • 通讯作者: 丁艳平 E-mail:dingyp05@163.com
  • 基金资助:
    青藏高原动物脑AQP4适应其极端低氧的分子机理

Protective effect of astragaloside on renal injury induced by radiation through toll-like receptor 4/nuclear factor kappa B pathway

XU Yu-qin1  DING Yan-ping1*  LIU Shu-ning1  KANG Jie1  SHAO Bao-ping2   

  1. 1. School of Life Science, Northwest Normal University, Lanzhou 730070, China; 2. School of Life Science, Lanzhou University, Lanzhou 730000, China
  • Received:2020-01-09 Revised:2020-07-07 Online:2021-08-06 Published:2021-08-06
  • Contact: DING Yan-ping E-mail:dingyp05@163.com

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摘要：

目的  探讨黄芪甲苷（AS-Ⅳ）是否通过toll样受体4（TLR4）/核因子κB（NF-κB）介导的信号通路对辐射诱导肾脏损伤起到保护作用。   方法  将小鼠分为正常对照组、DMSO溶剂组、辐射组(IR)、IR + AS-Ⅳ 20 mg/kg 组和IR + AS-Ⅳ 40 mg/kg 组。小鼠给予AS-Ⅳ腹腔注射1个月后，以8Gy的60Coγ进行全身辐射。测定血清肌酐（Cr）和尿酸（BUA）的含量，进行肾组织HE和免疫组织化学染色，并检测肾脏TLR4/NF-κB信号通路相关蛋白的表达情况。   结果  与对照组相比，辐射组小鼠血清中Cr和BUA含量明显升高（P<0.001），肾小球萎缩，肾小管扩张，TLR4和髓样分化因子88（MyD88）阳性表达明显增多(P<0.001)，且TLR4/NF-κB信号通路相关蛋白［TLR4、MyD88、NF-κB、白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）］表达极显著升高（P<0.01）；AS-Ⅳ预处理能降低血清中Cr和BUA的含量（P<0.05, P<0.01或 P<0.001），明显改善辐射所致的病理反应，降低TLR4/NF-κB 信号通路相关蛋白的表达（P<0.05或 P<0.01）。   结论  AS-Ⅳ可能通过TLR4/NF-κB信号通路下调炎症因子的释放，从而改善辐射诱导的小鼠肾损伤，发挥保护作用。

关键词: 黄芪甲苷, 肾损伤, 辐射, Toll样受体4, 核因子κB, 免疫炎症反应, 免疫组织化学, 小鼠

Abstract:

Objective  To explore whether astragaloside Ⅳ (AS-Ⅳ) can protect radiation-induced kidney injury through toll-like receptor 4（TLR4）/nuclear factor kappa B（NF-κB）-mediated signaling pathway.    Methods  The mice were randomly divided into normal control group, DMSO solvent group, irradiation group (IR), IR + AS-Ⅳ 20 mg/kg group and IR + AS-Ⅳ 40 mg/kg group. One month after intraperitoneal injection of AS-Ⅳ, the mice were irradiated with 8 Gy 60Coγ and to the content of serum creatinine (Cr) and uric acid (BUA) in serum were determined, HE and immunohistochemical staining, and expression of TLR4/NF-κB signaling pathway related protein in kidney were performed.    Results  Compared with the control group, the levels of Cr and BUA in the serum of the radiation group increased significantly (P<0.001), glomerular atrophy and tubular expansion, TLR4 and myeloid differentiation factor 88(MyD88) positive expression increased significantly (P<0.001), and the expression of TLR4/NF-κB signaling pathway-related proteins［TLR4, MyD88, NF-κB, interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α)］ increased significantly (P<0.01); AS-Ⅳ pretreatment can reduce the content of Cr and BUA in serum (P<0.05, P<0.01 or P<0.001), significantly improve the pathological response caused by radiation, and reduce the expression of TLR4/NF-κB signaling pathway-related proteins (P<0.05 or P<0.01).    Conclusion  AS-Ⅳ may down-regulate the release of inflammatory factors through the TLR4/NF-κB signaling pathway, thereby improving radiation-induced kidney injury in mice and playing a protective role.

Key words: Astragaloside Ⅳ, Kidney injury, Radiation, Toll-like receptor 4, Nuclear factor kappa B, Immunoinflammatory response, Immunohistochemistry, Mouse

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