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

doi:10.11958/20220965

天津医药 ›› 2023, Vol. 51 ›› Issue (1): 41-44.doi: 10.11958/20220965

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

王江涛¹^,²(), 马博华², 沈会华², 何佳², 尹东锋², 王瑞², 李悟²^,^∆()

1 石河子大学医学院（邮编832000）
2 新疆军区总医院

收稿日期:2022-06-21 修回日期:2022-07-19 出版日期:2023-01-15 发布日期:2023-01-17
通讯作者: 李悟 E-mail:wangjy909@163.com;goodli002@163.com
作者简介:王江涛（1997），男，硕士在读，主要从事高原肺动脉高压基础方面研究。E-mail：wangjy909@163.com
基金资助:
新疆自治区区域协同创新专项(2020E0290)

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

WANG Jiangtao¹^,²(), MA Bohua², SHEN Huihua², HE Jia², YIN Dongfeng², WANG Rui², LI Wu²^,^∆()

1 School of Medicine, Shihezi University, Shihezi 832000, China
2 General Hospital of Xinjiang Military Command

Received:2022-06-21 Revised:2022-07-19 Published:2023-01-15 Online:2023-01-17
Contact: LI Wu E-mail:wangjy909@163.com;goodli002@163.com

王江涛, 马博华, 沈会华, 何佳, 尹东锋, 王瑞, 李悟. 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[J]. 天津医药, 2023, 51(1): 41-44.

WANG Jiangtao, MA Bohua, SHEN Huihua, HE Jia, YIN Dongfeng, WANG Rui, LI Wu. The effect of halofuginone on cardiopulmonary function and its mechanism in rats with high-altitude pulmonary hypertension[J]. Tianjin Medical Journal, 2023, 51(1): 41-44.

摘要/Abstract

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。

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

Abstract:

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 and 2 mg/kg, respectively). The model group and the control group were given distilled water, once a day, for consecutive 4 weeks. 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 index in the high-dose group. Conclusion HF can reduce the mean pulmonary artery pressure, relieve right ventricular hypertrophy and improve pulmonary vascular remodeling in HAPH rats, and its mechanism may be related to the inhibition of HIF-1α, VEGF and ET-1 expressions.

Key words: DICHROA FEBRIFUGA, ketones, altitude, hypertension, pulmonary, vascular endothelial growth factors, endothelin-1, HIF-1α

中图分类号:

R563

图/表 3

参考文献 19

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组别	mPAP（mmHg）	RVHI（%）
对照组	15.16±0.48	22.93±1.79
模型组	37.48±0.71^a	54.29±4.90^a
低剂量组	32.00±0.76^b	45.08±5.28^b
中剂量组	23.57±3.17^bc	41.52±5.59^b
高剂量组	22.79±1.79^bc	39.47±2.34^b
F	259.020^＊＊	71.012^＊＊

组别	mPAP（mmHg）	RVHI（%）
对照组	15.16±0.48	22.93±1.79
模型组	37.48±0.71^a	54.29±4.90^a
低剂量组	32.00±0.76^b	45.08±5.28^b
中剂量组	23.57±3.17^bc	41.52±5.59^b
高剂量组	22.79±1.79^bc	39.47±2.34^b
F	259.020^＊＊	71.012^＊＊

组别	HIF-1α		VEGF		ET-1
组别	血清	肺组织	血清	肺组织	血清	肺组织
对照组	97.44±4.24	101.54±12.62	1 746.67±127.37	1 236.67±139.87	357.27±7.11	315.45±33.27
模型组	137.82±10.26^a	153.85±10.76^a	2 426.67±242.80^a	1 733.33±89.39^a	500.00±61.54^a	460.91±38.63^a
低剂量组	128.59±12.65	146.54±9.39	2 315.00±165.93	1 488.33±103.13^b	463.64±29.38	400.91±19.40^b
中剂量组	116.79±9.07^b	129.36±7.29^b	1 935.00±121.02^b	1 336.67±116.32^bc	394.09±38.70^b	359.55±30.23^bc
高剂量组	111.41±12.27^b	115.90±17.67^b	1 886.67±127.22^b	1 281.67±88.30^bc	374.09±19.62^b	331.36±36.82^bc
F	23.533^＊＊	31.739^＊＊	32.135^＊＊	34.113^＊＊	28.469^＊＊	32.724^＊＊

组别	HIF-1α		VEGF		ET-1
组别	血清	肺组织	血清	肺组织	血清	肺组织
对照组	97.44±4.24	101.54±12.62	1 746.67±127.37	1 236.67±139.87	357.27±7.11	315.45±33.27
模型组	137.82±10.26^a	153.85±10.76^a	2 426.67±242.80^a	1 733.33±89.39^a	500.00±61.54^a	460.91±38.63^a
低剂量组	128.59±12.65	146.54±9.39	2 315.00±165.93	1 488.33±103.13^b	463.64±29.38	400.91±19.40^b
中剂量组	116.79±9.07^b	129.36±7.29^b	1 935.00±121.02^b	1 336.67±116.32^bc	394.09±38.70^b	359.55±30.23^bc
高剂量组	111.41±12.27^b	115.90±17.67^b	1 886.67±127.22^b	1 281.67±88.30^bc	374.09±19.62^b	331.36±36.82^bc
F	23.533^＊＊	31.739^＊＊	32.135^＊＊	34.113^＊＊	28.469^＊＊	32.724^＊＊

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

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