CAJ | 학술논문

目的研究腺病毒携带肝细胞生长因子(HGF)转染对肺动脉高压(PAH)大鼠肺动脉压力,右心室系统及内皮膜微粒(EMP)的影响,探讨HGF治疗对PAH可能的作用机制.方法健康雄性SD大鼠40只,随机分为4组,正常对照组(NOR组)10只,野百合碱诱导的肺动脉高压组(PAH组)10只,HGF治疗肺动脉高压组(HGF和THGF组)各10只.NOR和PAH组:气道内滴注0.2 ml PBS液;HGF组:气道内滴注0.2 ml Ad-HGF 1次;THGF组:气道内滴注0.2 ml Ad-HGF 1次,1周后再重复气道内滴注Ad-HGF 0.2 ml共2次.不同的干预处理后两周,测定各组大鼠的平均肺动脉压(mPAP),计算右心室肥厚指数(RVHI),HE染色观察肺动脉管壁厚度指数(TI)和面积指数(AI),流式细胞术测定血浆内皮膜微粒的浓度.结果气道内滴注腺病毒携带HGF 2周后,HGF和THGF组mPAP、RVHI、TI、AI均较PAH组显著降低(P＜0.05);PAH组EMP浓度随时间点增加升高,不同时间点EMP浓度均明显高于对照组(P＜0.05).HGF组给药后7 d(59.1 ±2.8)、14 d(55.9±3.7)的EMP浓度较PAH组[(75.4±3.3)、(78.8±3.0)水平明显下降,仍高于NOR组(35.2±11.1)、(39.9±10.2),P＜0.05],且给药7d和14 d后HGF组EMP水平明显低于给药前[(69.5±2.8),P＜0.05].结论经气道内滴注转染HGF后,能较大程度降低肺动脉压力,可能通过抑制肺动脉管壁的增厚及保持有效管腔面积,延缓右心室肥厚,不能达到完全逆转的作用,作用机制可能通过降低内皮膜微粒水平,促进内皮细胞修复来达到干预肺动脉高压的治疗目标.
목적 연구선병독휴대간세포생장인자(HGF)전염대폐동맥고압(PAH)대서폐동맥압력,우심실계통급내피막미립(EMP)적영향,탐토HGF치료대PAH가능적작용궤제.방법 건강웅성SD대서40지,수궤분위4조,정상대조조(NOR조)10지,야백합감유도적폐동맥고압조(PAH조)10지,HGF치료폐동맥고압조(HGF화THGF조)각10지.NOR화PAH조:기도내적주0.2 ml PBS액;HGF조:기도내적주0.2 ml Ad-HGF 1차;THGF조:기도내적주0.2 ml Ad-HGF 1차,1주후재중복기도내적주Ad-HGF 0.2 ml공2차.불동적간예처리후량주,측정각조대서적평균폐동맥압(mPAP),계산우심실비후지수(RVHI),HE염색관찰폐동맥관벽후도지수(TI)화면적지수(AI),류식세포술측정혈장내피막미립적농도.결과 기도내적주선병독휴대HGF 2주후,HGF화THGF조mPAP、RVHI、TI、AI균교PAH조현저강저(P＜0.05);PAH조EMP농도수시간점증가승고,불동시간점EMP농도균명현고우대조조(P＜0.05).HGF조급약후7 d(59.1 ±2.8)、14 d(55.9±3.7)적EMP농도교PAH조[(75.4±3.3)、(78.8±3.0)수평명현하강,잉고우NOR조(35.2±11.1)、(39.9±10.2),P＜0.05],차급약7d화14 d후HGF조EMP수평명현저우급약전[(69.5±2.8),P＜0.05].결론 경기도내적주전염HGF후,능교대정도강저폐동맥압력,가능통과억제폐동맥관벽적증후급보지유효관강면적,연완우심실비후,불능체도완전역전적작용,작용궤제가능통과강저내피막미립수평,촉진내피세포수복래체도간예폐동맥고압적치료목표.
Objective To explore the effect of transfection of adenovirus carrying hepatocyte growth factor (HGF) on pulmonary arterial hypertension (PAH) and endothelial cell membrane microparticles (EMP) in a rat model,and the underlying mechanism.Methods Forty healthy male SD rats were randomly divided into four groups,the normal control group (NOR group),monocrotaline (MCT)-induced pulmonary hypertension group (PAH group),HGF treatment of PAH group (HGF group and THGF group) each with 10 rats.NOR group and the PAH Group:intratracheal instillation of 0.2 ml PBS solution; HGF group:intratracheal instillation of 0.2 ml HGF one times ; THGF Group:intratracheal instillation of 0.2 ml HGF one times,and then 1 week repeat again.Different interventions after 2 weeks,the rats was measured mean pulmonary arterial pressure,right ventricular hypertrophy index calculation,HE staining index of pulmonary arterial wall thickness,area index,plasma levels of endothelial cell microparticles.Results HGF intratracheal instillation after 2 weeks,HGF and THGF groups of SD rats mPAP,RVHI,TI,AI decreased significantly compared with PAH group (P ＜ 0.05).PAH group was increased in particulate levels at different time points significantly higher levels of horizontal (P ＜ 0.05).The EMP levels in HGF group which at 7 and 14 days after dosing were significantly decreased compared with PAH.It still higher than the NOR group (P ＜ 0.05).And after administration of 7 days,14 days,the EMP level of HGF group was significantly lower than before administration (P ＜ 0.05).Conclusions Thought airway instillation transfected HGF,pulmonary artery pressure can reduce greater degree,but can't achieve complete reversal.It can inhibit the pulmonary artery wall thickening and maintain effective lumen area,delaying the right ventricular hypertrophy by reducing the membrane particles within the lung,thereby promoting endothelial cell repair to achieve the goal of intervention in pulmonary hypertension.