常山酮对高原肺动脉高压模型大鼠心肺功能的影响及其机制研究  

The effect of halofuginone on cardiopulmonary function and its mechanism in rats with high-altitude pulmonary hypertension

作　　者：王江涛 马博华 沈会华[2] 何佳 尹东锋[2] 王瑞[2] 李悟[2] WANG Jiangtao;MA Bohua;SHEN Huihua;HE Jia;YIN Dongfeng;WANG Rui;LI Wu(School of Medicine,Shihezi University,Shihezi 832000,China;General Hospital of Xinjiang Military Command)

机构地区：[1]石河子大学医学院,832000 [2]新疆军区总医院

出　　处：《天津医药》2023年第1期41-44,共4页Tianjin Medical Journal

基　　金：新疆维吾尔自治区区域协同创新专项(2020E0290)。

摘　　要：目的 探讨常山酮(HF)对高原肺动脉高压(HAPH)模型大鼠心肺功能的影响及其机制。方法 根据随机数字表法从50只雄性SD大鼠中抽取40只,分为模型组和低、中、高剂量组,每组10只,于低压低氧舱中模拟海拔6 000 m高原环境构建HAPH大鼠模型;另10只作为对照组于舱外喂养。低、中、高剂量组予HF(给药剂量分别为0.5、1、2 mg/kg),模型组和对照组予等量蒸馏水,每天灌胃1次,连续4周。测定各组大鼠平均肺动脉压(mPAP),计算右心室肥厚指数(RVHI),苏木精-伊红(HE)染色评定肺血管重塑程度,酶联免疫吸附试验(ELISA)检测大鼠血清和肺组织低氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)、内皮素-1(ET-1)水平。结果 与对照组比较,模型组mPAP和RVHI均明显升高(P<0.05),肺小动脉管壁明显增厚、管腔狭窄,血清和肺组织HIF-1α、VEGF、ET-1水平均明显升高(P<0.05);与模型组比较,低、中、高剂量组mPAP和RVHI均明显降低(P<0.05),中、高剂量组肺血管重塑程度均显著减轻,血清和肺组织HIF-1α、VEGF、ET-1水平均明显降低,而低剂量组仅肺组织VEGF、ET-1含量降低(P<0.05);与低剂量组比较,中、高剂量组mPAP、肺组织VEGF及ET-1含量降低(P<0.05);与中剂量组比较,高剂量组各指标差异均无统计学意义。结论 HF能降低HAPH大鼠的mPAP、减轻右心室肥厚、改善肺血管重塑,其作用机制可能与抑制HIF-1α、VEGF及ET-1表达有关。Objective To investigate the effect of halofuginone(HF) on the cardiopulmonary function of rats with high-altitude pulmonary hypertension(HAPH) and its mechanism.Methods Forty male SD rats were selected according to random number table method and divided into the model group,the low-dose,the medium-dose and the high-dose groups,with 10 rats in each group.HAPH rat model was constructed in hypobaric hypoxia chamber simulating altitude of 6 000 m.The other 10 were fed outside the cabin as the control group.Low,medium and high dose groups were given HF(0.5,1 and2 mg/kg,respectively).The model group and the control group were given distilled water,once a day,for consecutive 4weeks.The mean pulmonary artery pressure(mPAP) was measured.The right ventricular hypertrophy index(RVHI) was calculated,and the degree of pulmonary vascular remodeling was assessed by hematoxylin-eosin(HE) staining.The levels of hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF) and endothelin-1(ET-1) in serum and lung tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the control group,the mPAP and RVHI were significantly increased in the model group(P <0.05).The small pulmonary artery wall was significantly thickened and the lumen was narrowed,and levels of HIF-1α,VEGF and ET-1 in serum and lung tissue were significantly increased(P <0.05).Compared with the model group,the mPAP and RVHI were significantly decreased in the low,medium and high dose groups(P <0.05).The degree of pulmonary vascular remodeling was significantly alleviated in the medium and high dose groups,and levels of HIF-1α,VEGF and ET-1 in serum and lung tissue were significantly decreased,while levels of VEGF and ET-1 in lung tissue were only decreased in the low-dose group(P <0.05).Compared with the low-dose group,the mPAP,VEGF and ET-1 in lung tissue were significantly decreased in the medium and high dose groups(P <0.05).Compared with the medium-dose group,there was no significant difference in each in

关 键 词：常山 酮类 高海拔 高血压 肺性 血管内皮生长因子类 内皮缩血管肽1 HIF-1Α 

分 类 号：R563[医药卫生—呼吸系统]