Astragalus polysaccharide protects mice against pulmonary vascular remodeling after hypoxia-induced pulmonary hypertension

Haiyan DENG; Meili LU; Hongxin WANG

doi:10.16016/j.2097-0927.202111144

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Astragalus polysaccharide protects mice against pulmonary vascular remodeling after hypoxia-induced pulmonary hypertension

Basic Medicine | 更新时间：2026-01-09

- Astragalus polysaccharide protects mice against pulmonary vascular remodeling after hypoxia-induced pulmonary hypertension
- Journal of Army Medical University Vol. 44, Issue 11, Pages: 1112-1118(2022)
- 作者机构：
  
  121001 辽宁锦州，锦州医科大学心脑血管药物研究重点实验室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81973553)
- DOI：10.16016/j.2097-0927.202111144
  CLC： R285.5;R322.12;R544
- Received：19 November 2021，
  
  Revised：2021-12-25，
  
  Published：15 June 2022
- 稿件说明：
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Haiyan DENG, Meili LU, Hongxin WANG. Astragalus polysaccharide protects mice against pulmonary vascular remodeling after hypoxia-induced pulmonary hypertension[J]. Journal of Army Medical University, 2022, 44(11): 1112-1118.
DOI：

Haiyan DENG, Meili LU, Hongxin WANG. Astragalus polysaccharide protects mice against pulmonary vascular remodeling after hypoxia-induced pulmonary hypertension[J]. Journal of Army Medical University, 2022, 44(11): 1112-1118. DOI： 10.16016/j.2097-0927.202111144.

摘要

目的

研究黄芪多糖(Astragalus polysaccharide，APS)对低氧诱导的肺动脉高压(hypoxic pulmonary hypertension，HPH)小鼠肺血管重构的影响并探讨其相关作用机制。

方法

将C57BL/6小鼠置于含10% O

的常压低氧舱中持续饲养4周制备肺动脉高压模型。50只雄性C57BL/6小鼠按完全随机法分为正常对照组，模型组，模型+APS 200、400、800 mg/kg组。4周后检测小鼠右心室收缩压(right ventricular systolic pressure，RVSP)、右心肥厚指数；HE染色观察肺小动脉病理变化；Masson染色观察肺小动脉胶原纤维沉积面积；组织免疫荧光检测肺小动脉α-SMA蛋白水平；ELISA检测血清C-反应蛋白(CRP)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)含量；Western blot检测肺组织KLF5、HIF-1α、Cyclin B1、Cyclin D1、VEGF、TGF-β1蛋白水平。

结果

与正常对照组相比，模型组小鼠RVSP、RV/(LV+S)显著增加，肺小动脉血管增厚，胶原纤维沉积面积增大，CRP、IL-6、TNF-α含量增加，α-SMA、KLF5、HIF-1α、Cyclin B1、Cyclin D1、VEGF、TGF-β1蛋白水平显著升高(

0.01)；与模型组相比，各APS治疗组小鼠RVSP、RV/(LV+S)、肺小动脉病理改变均不同程度减轻，胶原纤维沉积面积明显减少，CRP、IL-6、TNF-α含量降低，α-SMA、KLF5、HIF-1α、Cyclin B1、Cyclin D1、VEGF、TGF-β1蛋白水平显著降低(

0.01)。

结论

APS对低氧诱导的肺动脉高压小鼠肺血管重构具有保护作用，其作用机制可能与抑制KLF5/HIF-1α信号通路有关。

Abstract

Objective

To investigate the effects of astragalus polysaccharide (APS) on pulmonary vascular remodeling in mice with hypoxic pulmonary hypertension (HPH) and explore its related mechanism.

Methods

Fifty male C57BL/6 mice were randomly and equally divided into normal control group

model group

and model+APS (200

400 and 800 mg/kg) groups. The mice in the model and model+APS groups were kept in a normal pressure hypoxia chamber containing 10% O

for 4 weeks to prepare a pulmonary hypertension model. In 4 weeks later

right ventricular systolic pressure (RVSP) and right heart hypertrophy index RV/(LV+S) were measured. HE staining and Masson staining were used to observe the pathological changes and the collagen

deposition in the pulmonary arterioles

respectively. Immunofluorescence assay was adopted to detect the protein level of α-SMA in the pulmonary arterioles. The contents of serum C-reactive protein (CRP)

IL-6 and TNF-α were determined by ELISA

and the protein levels of Krüppel-like factor 5 (KLF5)

hypoxia-inducible factor 1α (HIF-1α)

Cyclin B1

Cyclin D1

VEGF and TGF-β1 in lung tissues were tested by Western blotting.

Results

As compared with the normal control group

the RVSP and RV/(LV+S) were significantly increased

the pulmonary arteriole wall was thickened

and the area of collagen deposition was enlarged in the model group. In addition

the contents of CRP

IL-6

TNF-α

and the protein levels of α-SMA

KLF5

HIF-1α

Cyclin B1

Cyclin D1

VEGF and TGF-β1 were all notably elevated in the model group (P < 0.01). In comparison with the model group

the RVSP

RV/(LV+S) and pathological changes of pulmonary arterioles were alleviated

the collagen deposition area was remarkably reduced

and the levels of CRP

IL-6

TNF-α

α-SMA

KLF5

HIF-1α

Cyclin B1

Cyclin D1

VEGF

TGF-β1 were greatly decreased in the APS treatment groups (P < 0.01).

Conclusion

APS shows a protective effect on pulmonary vascular remodeling in mice with hypoxia-induced pulmonary hypertension

which may be related to its inhibition on KLF5/HIF-1α signaling pathway.

关键词

Keywords

references

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