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  

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

作　　者：郭鑫 李明霞[2] 巴依尔才次克[2] 杨延青 王乐[2] GUO Xin;LI Ming-Xia;BAYER Caicike;YANG Yan-Qing;WANG Le(Department of Neonatology,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学儿科学院,新疆乌鲁木齐830054 [2]新疆医科大学第一附属医院新生儿科,新疆乌鲁木齐830054

出　　处：《中国当代儿科杂志》2023年第4期407-414,共8页Chinese Journal of Contemporary Pediatrics

基　　金：国家自然科学基金(82060287)。

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13μL 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。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 13μL 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

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 

分 类 号：R725.4[医药卫生—儿科]