Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease

DUAN Yafei; SHI Xiancong; ZHAO Liang; LYU Mingzhen; REN Xinqi; GU Yulei; XU Jiangyan; ZHANG Zhenqiang; MIAO Jinxin; XIE Zhishen; ZHANG Xiaowei

doi:10.3969/j.issn.1006-2157.2024.10.011

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Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease

Experimental Study | 更新时间：2024-10-29

- Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease
- Journal of Beijing University of Traditional Chinese Medicine Vol. 47, Issue 10, Pages: 1408-1415(2024)
- 作者机构：
  
  1.河南中医药大学中医药科学院　郑州　450046
  2.河南中医药大学豫药全产业链研发河南省协同创新中心
  3.河南中医药大学中医学院
- 作者简介：
  
  ZHANG Xiaowei, Ph.D., Assistant Research, Master′s Supervisor. Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, No. 156, Jinshui Donglu Road, Jinshui District, Zhengzhou 450046. E-mail: zhangxw2020@163.com
- 基金信息：
  
  National Key R&D Program of China(2020YFE0201800);Natural Science Foundation of China(82104471);Henan Provincial Key Research and Development Program(221111520300)
- DOI：10.3969/j.issn.1006-2157.2024.10.011
  CLC： R285.5
- Received：24 June 2024，
  
  Online First：20 August 2024，
  
  Published：30 October 2024
- 稿件说明：
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DUAN Yafei, SHI Xiancong, ZHAO Liang, et al. Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease[J]. Journal of Beijing University of Traditional Chinese Medicine, 2024, 47(10): 1408-1415.
DOI：

DUAN Yafei, SHI Xiancong, ZHAO Liang, et al. Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease[J]. Journal of Beijing University of Traditional Chinese Medicine, 2024, 47(10): 1408-1415. DOI： 10.3969/j.issn.1006-2157.2024.10.011.

摘要

目的

探讨黄芪活性成分黄芪皂苷Ⅰ抑制足细胞损伤、改善糖尿病肾脏疾病的作用机制。

方法

60只雄性db/db小鼠按体质量随机分为模型组、黄芪皂苷Ⅰ低剂量组(10 mg/kg)、黄芪皂苷Ⅰ中剂量组(20 mg/kg)、黄芪皂苷Ⅰ高剂量组(40 mg/kg)及缬沙坦组(10 mg/kg)，每组12只；12只db/db同窝对照db/m小鼠作为对照组。灌胃给药8周。透射电子显微镜观察肾脏超微结构；免疫组织化学法、蛋白质印迹法检测肾脏足细胞标志物肾病蛋白(nephrin)的表达情况；酶联免疫吸附测定法检测小鼠血清白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)含量；蛋白质印迹法检测肾脏组织NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶-1(Caspase-1)、消皮素D(GSDMD)蛋白表达。

结果

与对照组比较，模型组小鼠肾小球出现明显的足细胞丢失、足突融合等现象；肾脏nephrin蛋白表达下降(

0.05)；血清IL-1β、IL-18含量升高(均

0.05)；NLRP3、裂解型Caspase-1(Cleaved-Caspase-1)、GSDMD-N蛋白表达升高(均

0.05)。与模型组比较，黄芪皂苷Ⅰ给药组肾脏病理损伤得到缓解；Nephein蛋白表达升高(

0.05)；血清IL-1β、IL-18含量下降(均

0.05)；NLRP3、Cleaved-Caspase-1、GSDMD-N蛋白表达下降(均

0.05)。

结论

黄芪皂苷I可能通过抑制细胞焦亡、改善足细胞损伤发挥干预糖尿病肾脏疾病的作用。

Abstract

Objective

To investigate the mechanism of astragaloside I

the active constituent of milkvetch root

in inhibiting podocyte injury and improving diabetic kidney disease.

Methods

According to the body weight

60 male db/db mice were randomly divided into the model group

astragaloside Ⅰ low-dose group (10 mg/kg)

astragaloside I medium-dose group (20 mg/kg)

astragaloside I high-dose group (40 mg/kg)

and valsartan group (10 mg/kg)

with 12 mice per group. Twelve db/db littermate control db/m mice were used as the control group. The drug was administered by gavage for 8 weeks. Transmission electron microscope was used to observe the ultrastructure of the kidney; immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein (nephrin)

a marker of renal podocytes; enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the serum of mice; Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3 (NLRP3)

cysteinyl aspartate specific proteinase 1 (Caspase-1)

and Gasdermin D (GSDMD) in kidney tissue.

Results

Compared with the control group

the glomeruli of the model group showed obvious podocyte loss and foot process fusion; the protein expression of nephrin was decreased (

0.05); the contents of IL-1β and IL-18 in serum were increased (

0.05); the protein expressions of NLRP3

Cleaved-Caspase-1

and GSDMD-N were increased (

0.05). Compared with the model group

the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated; the protein expression of nephrin was increased (

0.05); the contents of IL-1β and IL-18 in serum were decreased (

0.05); the protein expressions of NLRP3

Cleaved-Caspase-1

and GSDMD-N were decreased (

0.05).

Conclusion

Astragaloside I may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.

关键词

Keywords

references

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