Astragaloside IV improves podocyte injury and mitochondrial dysfunction induced by high glucose and inhibits Notch pathway activation
- VernacularTitle:黄芪甲苷改善高糖诱导的足细胞损伤和线粒体功能障碍并抑制Notch通路激活
- Author:
Xiaojie MIAO
1
;
Dingkun GUI
2
;
Yuqiang CHEN
2
;
Rong LÜ
1
;
Daohong LI
1
;
Xufeng YANG
1
Author Information
- Publication Type:Journal Article
- Keywords: astragaloside IV; podocyte injury; mitochondrial dysfunction; Notch pathway
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):135-141
- CountryChina
- Language:Chinese
- Abstract: 【Objective】 To investigate the protection of astragaloside IV from high glucose induced podocyte injury and mitochondrial dysfunction and its molecular mechanisms. 【Methods】 The model of podocyte injury induced by high glucose (30 mmol/L glucose) was established, and the model cells were treated with low, medium and high doses of astragaloside IV respectively; cell activity was detected by CCK-8. Apoptosis was detected by TUNEL staining. Mitochondrial membrane potential was detected by JC-1 fluorescence probe. ATP content was detected by the kit. The expression levels of apoptosis and podocyte injury related proteins and Notch pathway related proteins were detected by Western blotting. 【Results】 Compared with the control group, cell activity was decreased, apoptosis level was increased (P<0.05), anti-apoptotic protein (Bcl2) expression was decreased, and apoptosis protein (Bax, cleaved-caspase 9, cleaved-caspase 3) expressions were increased (all P<0.05) in HG group. Compared with HG group, HG+AS-IV improved cell activity and apoptosis level induced by high glucose (P<0.05), increased expression of anti-apoptotic protein (Bcl2), and decreased expressions of apoptotic protein (Bax, cleaved-caspase 9, and cleaved-caspase 3) (all P<0.05). Compared with the control group, mitochondrial dysfunction occurred in HG group, JC-1 monomer content increased, and ATP content decreased (all P<0.05). Compared with HG group, HG+AS-IV improved mitochondrial dysfunction, increased JC-1 polymer content and ATP content (P<0.05). In addition, compared with the control group, the expression of Notch pathway-related protein was decreased in HG group (P<0.05). Compared with HG group, Notch pathway-related protein expression was increased in HG+AS-IV group (all P<0.05). Molecular docking results showed that AS-IV could bind Notch1. 【Conclusion】 Astragaloside IV can improve podocyte injury and mitochondrial dysfunction induced by high glucose, possibly by inhibiting Notch pathway activation.
