早期肝细胞生长因子转基因治疗对肺动脉高压大鼠细胞因子表达及肺血管和右心室重塑的影响  

Early treatment with hepatocyte growth factor improves pulmonary artery and right ventricular remodeling in rats with pulmonary artery hypertension by modulating cytokines expression

作　　者：王晓林[1] 王庸晋[2] 荣书玲[2] 马红彪[1] 

机构地区：[1]长治医学院附属和平医院儿科,山西046000 [2]长治医学院附属和平医院心内科,山西046000

出　　处：《中华结核和呼吸杂志》2014年第6期427-432,共6页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：山西省基础研究计划项目（2012011040-3,2013011049-4）;长治市科技计划项目（20123060）

摘　　要：目的 探讨早期肝细胞生长因子（HGF）转基因治疗对肺动脉高压大鼠细胞因子表达及肺血管和右心室重塑的影响.方法 30只SD大鼠按随机数字表法分为3组,每组10只,其中2组腹腔注射野百合碱建立大鼠肺动脉高压模型,作为空病毒转染组（模型组）和HGF基因转染组（HGF组）;另外10只腹腔注射生理盐水作为对照组（对照组）.HGF组经气管内滴入法转染携带HGF基因的重组腺病毒,模型组气管内滴入空病毒.4周后,组织学检测肺血管及右心室重塑,半定量逆转录-PCR（RT-PCR）检测重塑的肺血管及右心室心肌组织中肿瘤坏死因子（TNF）-α、IL-6、IL-1β和转化生长因子（TGF）-β1的表达量.结果 治疗4周后,模型组大鼠肺血管组织中TNF-α相对表达量为（0.82 ±0.07）,IL-6为（1.13 ±0.19）,IL-1β为（0.86±0.11）,TGF-β1为（1.18 ±0.12）,均高于对照组,差异有统计学意义（P＜0.05）.HGF组大鼠肺血管中TNF-α为（0.49 ±0.09）,IL-6为（0.68±0.09）,IL-1β为（0.51 ±0.07）,TGF-β1为（0.59 ±0.10）;右心室心肌TNF-α为（0.48 ±0.08）,IL-6为（0.63 ±0.09）,IL-1β为（0.52 ±0.07）,TGF-β1为（0.53 ±0.10）,均低于模型组,差异有统计学意义（P＜0.05）.与对照组相比模型组大鼠肺血管管壁厚度与外径的比值、管壁面积与血管总面积的比值、右心室肥厚指数、右心室心肌细胞横截面积及右心室胶原容积分数均较高（P＜0.05）,HGF治疗后上述指标明显改善.结论 早期HGF治疗可改善肺动脉高压大鼠肺血管及右心室重塑,可能与降低肺血管及右心室心肌组织中TNF-α、IL-6、IL-1β和TGF-β1的表达有关.Objective To investigate the effect of early treatment with hepatocyte growth factor （HGF） on the cytokine expression and pulmonary artery,right ventricular （RV） remodeling in the rat model of pulmonary artery hypertension （PAH）.Methods The rat model of PAH was produced by injecting monocrotaline,and the model rats were randomly divided into empty adenovirus transfection group （MCT group,n =10） and HGF gene transfection group（HGF group,n =10）.Another group of rats served as the Sham operation group （Sham group n =10）.After 4 weeks of HGF gene transfection,the histological sections of the lungs and right ventricular （RV） were stained with hematoxylin-eosin （HE） and the pulmonary artery and RV remodeling were examined.The rat lung sections were also immunostained with antibodies against factor Ⅷ,and the capillary density were calculated.Meanwhile,the mRNA expression of TNF-α,IL-6,IL-1β and TGF-β1 in pulmonary arteries and RV were detected by RT-PCR.Results HGF gene treatment significantly decreased the ratio of vessel wall thickness to pulmonary artery diameter and the ratio of vessel wall area to total area,and increased the capillary density of lung in PAH rats.HGF gene treatment also significantly decreased cross-sectional area of cardiomyocytes and collagen deposited in RV.Moreover,HGF gene treatment significantly decreased the expression of cytokines in pulmonary artery （TNF-α：0.82 ± 0.07 vs 0.49 ± 0.09,IL-6：1.13 ± 0.19 vs 0.68 ± 0.09,IL-1 β：0.86 ± 0.11 vs 0.51 ±0.07,TGF-β1：1.18 ± 0.12 vs 0.59 ± 0.10） and RV （TNF-α：0.79 ± 0.11 vs 0.48 ± 0.08,IL-6：1.03 ±0.11vs0.63±0.09,IL-1β：0.81±0.11 vs 0.52±0.07,TGF-β1：0.94 ±0.12 vs0.53±0.10） in MCT induced PAH rats （P 〈 0.05）.Conclusion Early treatment with HGF improves pulmonary artery and RV remodeling,possibly by decreasing the expression of TNF-α,IL-6,IL-1β and TGF-β1 in pulmonary arteries and RV.

关 键 词：高血压 肺性 心室重塑 细胞因子类 肝细胞生长因子 

分 类 号：R544.1[医药卫生—心血管疾病]