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_(2)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[RV/(LV+S)];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(P<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(P<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。
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 C57 BL/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_(2)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 ofα-SMA in the pulmonary arterioles.The contents of serum C-reactive protein(CRP),IL-6 and TNF-αwere 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 ofα-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-1αsignaling pathway.
作者
邓海艳
鲁美丽
王洪新
DENG Haiyan;LU Meili;WANG Hongxin(Key Laboratory of Cardiovascular and Cerebrovascular Drug Research,Jinzhou Medical University,Jinzhou,Liaoning Province,121001,China)
出处
《陆军军医大学学报》
CAS
CSCD
北大核心
2022年第11期1112-1118,共7页
Journal of Army Medical University
基金
国家自然科学基金面上项目(81973553)
