血小板源性生长因子-BB对缺氧性肺动脉高压新生大鼠肺血管重塑的影响及机制研究

郭鑫, 李明霞, 巴依尔才次克, 杨延青, 王乐

中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (4) : 407-414.

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中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (4) : 407-414. DOI: 10.7499/j.issn.1008-8830.2212002
论著·实验研究

血小板源性生长因子-BB对缺氧性肺动脉高压新生大鼠肺血管重塑的影响及机制研究

  • 郭鑫1, 李明霞2, 巴依尔才次克2, 杨延青1, 王乐2
作者信息 +

Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism

  • GUO Xin, LI Ming-Xia, BAYER Caicike, YANG Yan-Qing, WANG Le
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摘要

目的 探讨血小板源性生长因子-BB(platelet-derived growth factor-BB,PDGF-BB)对缺氧性肺动脉高压(hypoxia pulmonary hypertension,HPH)新生大鼠肺血管重塑的影响。 方法 128只新生大鼠随机分为:PDGF-BB+HPH组、HPH组、PDGF-BB+常氧组、常氧组(各组n=32)。PDGF-BB+HPH组、PDGF-BB+常氧组经尾静脉注射13 μL 6×1010 PFU/mL携带PDGF-BB基因的腺病毒载体。转染腺病毒载体24 h后,HPH组和PDGF-BB+HPH组建立HPH新生大鼠模型。缺氧3、7、14、21 d检测右心室收缩压(right ventricular systolic pressure,RVSP),苏木精-伊红染色后光学显微镜下观察肺血管形态学变化及血管重塑指标(MA%、MT%),免疫组化法检测肺组织中PDGF-BB、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达水平。 结果 PDGF-BB+HPH组和HPH组RVSP在各时间点均高于同日龄常氧组(P<0.05)。PDGF-BB+HPH组缺氧3 d出现血管重塑,HPH组缺氧7 d开始出现血管重塑;缺氧3 d时,PDGF-BB+HPH组MA%、MT%高于HPH组、PDGF-BB+常氧组、常氧组(P<0.05);缺氧7、14、21 d时,PDGF-BB+HPH组和HPH组MA%、MT%均高于PDGF-BB+常氧组、常氧组(P<0.05)。PDGF-BB+HPH组、HPH组在各时间点PDGF-BB、PCNA表达均高于常氧组(P<0.05),缺氧3、7、14 d时,PDGF-BB+HPH组PDGF-BB、PCNA表达高于HPH组(P<0.05),PDGF-BB+常氧组PDGF-BB、PCNA表达较常氧组高(P<0.05)。 结论 外源性给予HPH新生大鼠PDGF-BB,可上调PCNA表达,促进肺血管重塑,提高肺动脉压力。 [中国当代儿科杂志,2023,25(4):407-414]

Abstract

Objective To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH). Methods A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB gene via the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue. Results The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05). Conclusions Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(4): 407-414

关键词

血小板源性生长因子-BB / 肺动脉高压 / 血管重塑 / 增殖 / 新生大鼠

Key words

Platelet-derived growth factor-BB / Pulmonary hypertension / Vascular remodeling / Proliferation / Neonatal rat

引用本文

导出引用
郭鑫, 李明霞, 巴依尔才次克, 杨延青, 王乐. 血小板源性生长因子-BB对缺氧性肺动脉高压新生大鼠肺血管重塑的影响及机制研究[J]. 中国当代儿科杂志. 2023, 25(4): 407-414 https://doi.org/10.7499/j.issn.1008-8830.2212002
GUO Xin, LI Ming-Xia, BAYER Caicike, YANG Yan-Qing, WANG Le. Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(4): 407-414 https://doi.org/10.7499/j.issn.1008-8830.2212002

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基金

国家自然科学基金(82060287)。

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