气道内滴注肝细胞生长因子对野百合碱诱导肺动脉高压大鼠的干预研究  

Effect of intratracheal instillation of hepatocyte growth factor in rats with pulmonary hypertension induced by monocrotaline

作　　者：刘珍君[1] 王俊贤[1] 张如俊[1] 何忠开[1] 陈建英[1] 

机构地区：[1]广东医学院附属医院心血管内科二区,广东湛江524001

出　　处：《岭南心血管病杂志》2014年第5期657-661,共5页South China Journal of Cardiovascular Diseases

基　　金：广东省科技计划项目(项目编号:2009B030801378)

摘　　要：目的通过气道内滴注腺病毒转染肝细胞生长因子(adenovirus hepatocyte growth factor,Ad-HGF)干预野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary hypertension,PAH)模型大鼠,观察Ad-HGF干预对平均肺动脉压(mean pulmonary artery pressure,mPAP)等指标的影响。方法选用健康雄性SD大鼠40只,随机[采用随机单位(区)组设计方法]分为4组:正常对照组(normal,NOR组)10只,MCT诱导PAH组(PAH组)10只、单次和重复肝细胞生长因子(hepatocyte growth factor,HGF)干预治疗组(HGF和THGF组)各10只。NOR组和PAH组:气道内滴注0.2 mL磷酸盐缓冲液;HGF组和THGF组:气道内滴注0.2 mL Ad-HGF 1次和一周后重复一次共2次。再饲养两周后,测定各组大鼠的肺动脉压,计算右心室肥厚指数;苏木素伊红染色观察肺动脉管壁等;酶联免疫吸附(ELISA)法测定肺组织匀浆中HGF浓度。结果与PAH组大鼠比较,HGF组和THGF组大鼠的mPAP、右心室肥厚指数、肺动脉管壁指数和面积指数明显降低,肺苏木素伊红染色肺小动脉管壁厚度减少,管腔面积增大,血管周围炎症细胞浸润减轻,肺组织匀浆HGF浓度明显升高,差异有统计学意义(P<0.05),且低于NOR组水平。结论经气道内滴注转染Ad-HGF,能明显降低但不能完全逆转MCT诱导PAH大鼠的mPAP,减少肺小动脉管壁厚度,减轻右心室肥厚程度,从而达到延缓PAH进程的作用。Objectives To explore the effect of intratracheal instillation of adenovirus hepatocyte growth factor （Ad-HGF）in Sprague-Dawley rats with pulmonary hypertension （PAH） induced by monocrotaline （MCT）.Methods Totally 40 healthy male SD rats were randomly （random with district group design method） divided into 4 groups：10 in normal control group （NOR group）,10 in MCT-induced PAH group （PAH group）,10 in Ad-HGF treatment PAH group （HGF group）and 10 in THGF group （repeated HGF treatment in 1 week）.Rats in NOR group and PAH group were treated with intratracheal instillation of phosphate buffered saline （0.2 mL）.Rats in HGF group and THGF group were treated with intratracheal instillation of Ad-HGF （0.2 mL） at baseline and one week later.Two more weeks later,mean pulmonary artery pressure （mPAP） of rats in the 4 groups were measured; right ventricular hypertrophy index （RVHI） was calculated ; hematoxylin and eosin staining of pulmonary arterial wall thickness and area were obversed ; concentrations of HGF in lung tissues were determined by enzyme-linked immunosorbent assay （ELISA）.Results Two weeks later,mPAP,RVHI,pulmonary arterial wall thickness and area in HGF and THGF groups were significantly lower than those in PAH group （P〈0.05）.Pulmonary arterial wall thickness in lung tissues of HGF and THGF groups decreased,luminal cross-sectional area increased and inflammatory cell infiltration decreased compared with PAH group （P〈0.05）.Concentrations of HGF in lung tissues of HGF and THGF groups were significantly higher than that of PAH group （P〈0.05）,but lower than that of NOR group.Conclusions After intratracheal instillation of Ad-HGF,mPAP can be significantly reduced but not completely reversed in rats with PAH induced by MCT.By reducing wall thickness of pulmonary artery and degree of right ventricular hypertrophy,Ad-HGF may delay the process of PAH.

关 键 词：肺动脉高压 肝细胞生长因子 野百合碱 大鼠 

分 类 号：R543.2[医药卫生—心血管疾病]