摘要
目的探究地黄水提物对低氧诱导的肺动脉高压(pulmonary hypertension,PH)小鼠的干预作用。方法将60只小鼠随机分为正常组、模型组、波生坦组以及地黄低、中、高剂量组。除正常组外,其余各组均在10%的低氧环境中持续造模35 d,并于第21天开始给药。检测各组小鼠心功能(右心室压力、右心肥大指数、右心室与左心室的面积比),肺功能(呼吸频率、潮气量、每分钟通气量、最大吸气流速、最大呼气流速、50%潮气量时呼气流速、肺动脉血流速度、肺动脉血流加速时间与右心室射血时间比值),肺组织病理变化(苏木精-伊红染色、马松染色)氧化应激水平(丙二醛、超氧化物歧化酶、谷胱甘肽过氧化物酶和活性氧)、凋亡和免疫细胞的水平(巨噬细胞、中性粒细胞、Treg细胞),以评价不同剂量地黄水提物对PH小鼠的干预作用。蛋白质印迹法(WB)、免疫荧光检测各组小鼠肺组织中磷酸化细胞外信号调节激酶(p-ERK)和缺氧诱导因子-1α(HIF-1α)蛋白表达水平。结果地黄水提物可显著改善PH小鼠的心功能与肺功能,降低PH小鼠体内氧化应激、凋亡水平,调节免疫细胞水平,降低p-ERK和HIF-1α蛋白表达水平。结论地黄水提物通过ERK/HIF-1α改善低氧诱导PH小鼠的心肺损伤。
OBJECTIVE To investigate the intervention effect of the aqueous extract of Rehmannia glutinosa(RG)on hypoxia-induced pulmonary hypertension(PH)in mice.METHODS A total of 60 mice were randomly divided into control,model,bosentan(Bos),and the low,medium,and high dose RG(RC-L,RG-M,RG-H)groups.Except for the control group,the other groups were continuously established in 10%hypoxia environment for 35 d,and the drug was given on the 21st day.The cardiac function(right ventricular pressure,right ventricular hypertrophy index,right ventricular/left ventricular area ratio)and pulmonary function(respira-tory rate,tidal volume,minute volume,peak inspiratory flow,peak expiratory flow,expiratory flow 50%,pulmonary artery blood flow velocity,pulmonary artery acceleration time/right ventricular ejection time ratio)were measured.The levels of oxidative stress(malon-dialdehyde,superoxide dismutase,glutathione peroxidase and reactive oxygen species),apoptosis and immune cells(macrophages,neutrophils,Treg cells)in lung tissue were measured to evaluate the intervention effect of different doses of RG on PH mice.Western blotting and immunofluorescence were used to detect the protein expression levels of p-ERK and HIF-b in lung tissue of mice in each group.RESULTS RG significantly improved cardiac and lung function,reduced oxidative stress and apoptosis,regulated the level of immune cells,reduced the protein expression levels of p-ERK and HIF-1α in mice model of PH.CONCLUSION RG can improve car-diopulmonary injury in mice with hypoxia-induced PH through ERK/HIF-1αsignaling pathway.
作者
张宇涵
曾梦楠
郭彭莉
陈旭
张梓玉
郑晓珂
冯卫生
ZHANG Yuhan;ZENG Mengnan;CUO Pengli;CHEN Xu;ZHANG Ziyu;ZHENG Xiaoke;FENG Weisheng(Henan University of Chinese Medicine,Zhengzhou 450046,China;The Engineering and Technology Center for Chinese Medicine Development of Henan Province,Zhengzhou 450046,China;Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-construction by Henan Province and Ministry of Education of P.R.China,Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中国药学杂志》
北大核心
2025年第19期2035-2045,共11页
Chinese Pharmaceutical Journal
基金
国家重点研发计划-中医药现代化研究专项资助(2019YFC1708802,2017YFC1702800)
河南省重大科技专项资助(171100310500)
河南省高层次人才特殊支持计划“中原千人计划”-中原领军人才项目资助(ZYQR201810080)。
