摘要
背景:CD40通路的激活对内皮祖细胞的疗效起负向调节作用,而抑制该通路能增强内皮祖细胞的生物学功能。目的:比较CD40基因沉默的内皮祖细胞(shRNA-CD40转染内皮祖细胞)与常规内皮祖细胞移植治疗肺动脉高压模型的疗效,并探讨黄芪总苷在内皮祖细胞移植治疗肺动脉高压中的干预作用。方法:将90只SD大鼠以随机数字表法分为5组,分别为正常对照组(n=24)、模型组(n=24)、慢病毒转染组(n=18)、常规移植组(n=18)及黄芪总苷组(n=6)。除正常对照组外,其余4组均以野百合碱诱发肺动脉高压模型,慢病毒转染组大鼠分别于野百合碱注射后第7,14,21天尾静脉注射Lv-shRNA-CD40转染的内皮祖细胞,每个时间点6只;常规移植组大鼠分别于野百合碱注射后第7,14,21天尾静脉注射内皮祖细胞,每个时间点6只;黄芪总苷组在野百合碱注射后第21天时间点注射Lv-shRNA-CD40转染的内皮祖细胞,同时在第1-21天每日一次给予80 mg/(kg·d)黄芪总苷腹腔注射。野百合碱注射后第28天,进行血流动力学、血浆内皮素1水平与右心室肥大指数检测。结果与结论:(1)与正常对照组比较,模型组右心室压力、平均肺动脉压、右心室肥大指数均升高(P<0.05)。与模型组比较,慢病毒转染组、常规移植组右心室压力、平均肺动脉压、右心室肥大指数均明显下降(P<0.05)。随着移植内皮祖细胞时间的延长,2个细胞移植组右心室压力、平均肺动脉压、右心室肥大指数均有逐渐升高趋势,但慢病毒转染组变化差异不明显;(2)与正常对照组比较,模型组大鼠血浆内皮素1水平升高(P<0.05);与模型组比较,慢病毒转染组、常规移植组血浆内皮素1水平降低(P<0.05);慢病毒转染组相同移植时间点的血浆内皮素1水平低于常规移植组(P<0.05);(3)黄芪总苷组的血流动力学、血浆内皮素1水平及右心室肥大指数均优于慢病毒转染组(P<0.05);(4)结果表明,CD40基因
BACKGROUND:Activation of CD40 pathway negatively regulates the therapeutic effect of endothelial progenitor cells(EPCs),while inhibition of this pathway can enhance the biological function of the cells.OBJECTIVE:To compare the therapeutic effects of CD40-silenced EPCs(EPCs shRNA-CD40)and conventional EPCs transplantation in an animal model of pulmonary hypertension,and to explore the interventional effect of astragalosides on EPCs transplantation in the treatment of pulmonary hypertension.METHODS:Ninety SD rats were randomly divided into five groups:normal control group(n=24),model group(n=24),lentivirus transfection group(n=18),conventional transplantation group(n=18)and astragaloside group(n=6).Except the normal control group,the remaining four groups were given monocrotaline to induce pulmonary hypertension.Rats in the lentivirus transfection and conventional transplantation groups were given intravenous injection of Lv-shRNA-CD40-transfected EPCs and conventional EPCs respectively at 7,14,21 days after modeling(n=6 at each time point).Rats in the astragaloside group were given daily intraperitoneal injection of 80 mg/(kg?d)astragaloside within 1-21 days after modeling,and then Lv-shRNA-CD40-transfected EPCs were intravenously injected at 21 days after modeling.Hemodynamics,plasma endothelin-1 level and right ventricular hypertrophy index were detected at 28 days after modeling.RESULTS AND CONCLUSION:(1)After modeling,right ventricular pressure,mean pulmonary arterial pressure and right ventricular hypertrophy index were all increased compared with the normal control group(P<0.05),while these indices were then decreased significantly after EPCs transplantation(P<0.05).With the increasing of transplantation time,there was an increasing trend in the right ventricular pressure,mean pulmonary arterial pressure and right ventricular hypertrophy index in the two EPCs transplantation groups,but this trend was not remarkable in the lentivirus transfection group.(2)After modeling,the level of endothelin-1 was increased
作者
周小雄
魏伟超
孙策
叶桃春
王嵩
卿立金
吴辉
冼绍祥
Zhou Xiao-xiong;Wei Wei-chao;Sun Ce;Ye Tao-chun;Wang Song;Qing Li-jin;Wu Hui;Xian Shao-xiang(Department of Cardiovascular Medicine,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510400,Guangdong Province,China;Guangzhou University of Chinese Medicine,Guangzhou 510006,Guangdong Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2018年第9期1425-1431,共7页
Chinese Journal of Tissue Engineering Research
基金
广东省医学科学技术研究基金(A2016606);广东省高水平大学建设项目
关键词
高血压
肺性
内皮细胞
慢病毒感染
CD40配体
黄芪
组织工程
Hypertension,Pulmonary
Endothelial Cells
Lentivirus Infections
CD40 Ligand
Astragalus membranaceus
Tissue Engineering