伊马替尼对醋酸去氧皮质酮诱导的盐敏感性高血压大鼠心肌纤维化的干预作用  

Effect of imatinib on myocardial fibrosis in DOCA-salt hypertensive rats

作　　者：李谦[1] 马礼坤[1] 何立峰[1] 华锦胜[1] 周俊岭[1] 

机构地区：[1]安徽医科大学附属省立医院心血管内科,安徽合肥230001

出　　处：《中国病理生理杂志》2012年第1期53-58,共6页Chinese Journal of Pathophysiology

摘　　要：目的:研究血小板源性生长因子受体拮抗剂伊马替尼(IMA)对醋酸去氧皮质酮(DOCA)诱导的盐敏感性高血压大鼠心肌纤维化的干预作用及相关机制。方法:60只雄性SD大鼠行右肾切除术,术后给予1%NaCl和0.2%KCl饮水4周并随机分为3组:对照组(control组);DOCA组;DOCA+IMA组。尾套法测定大鼠动脉收缩压(SBP),HE染色观察心肌组织炎症反应情况,苦味酸-天狼星红染色观察大鼠心肌间质胶原容积分数(CVF)和血管周围胶原面积比(PVCA),免疫组化法观察心肌组织单核巨噬细胞抗原(ED-1)表达,免疫印迹法检测血小板源性生长因子(PDGF-A和PDGF-C)、血小板源性生长因子受体α(PDGFRα)和磷酸化血小板源性生长因子受体α(p-PDGFRα)表达。结果:(1)DOCA组和DOCA+IMA组大鼠SBP显著升高,两组相比无显著差异(P>0.05),但均显著高于对照组(P<0.01);(2)DOCA组出现严重心肌纤维化,其CVF和PVCA值明显高于对照组(P<0.01),DOCA+IMA组CVF和PVCA值虽高于对照组(P<0.05),但较DOCA组显著减小(P<0.05);(3)与对照组相比,DOCA组及DOCA+IMA组心肌间质可见明显炎症渗出及单核巨噬细胞浸润;(4)DOCA组及DOCA+IMA组PDGF-A、PDGF-C和PDGFRα表达均明显高于对照组(P<0.01),但DOCA+IMA组p-PDGFRα表达较DOCA组明显减少(P<0.05)。结论:盐皮质激素致心肌纤维化与心肌组织炎症反应、单核巨噬细胞浸润增加及PDGF-A、PDGF-C、PDGFRα表达增多有关,应用伊马替尼可以抑制这一纤维化过程,其机制可能与其抑制成纤维细胞表面PDGFRα活性、中断PDGFs信号途径介导的成纤维细胞分裂增殖相关。AIM： To investigate the effects of imatinib（IMA）,one of platelet-derived growth factor receptor（PDGFR） inhibitors,on myocardial fibrosis in deoxycorticosterone acetate（DOCA）-salt hypertensive rats.METHODS： Sixty male uninephrectomized SD rats were treated with 1% NaCl and 0.2% KCl in the drinking water for 4 weeks and assigned to 3 groups： vehicle control group（control group）,DOCA treatment group（DOCA group）,DOCA and IMA treatment group（DOCA＋IMA group）.Systolic blood pressure（SBP） was measured using the tail-cuff method.Myocardial tissue inflammation was analyzed by hematoxylin-eosin staining.Collagen volume fraction（CVF） and perivascular collagen area（PVCA） were analyzed by Sirius red staining.Ectodermal dysplasia-1（ED-1） was analyzed by immunohistochemistry.Expression levels of platelet-derived growth factors（PDGF-A and PDGF-C）,PDGF receptor α（PDGFRα） and phosphorylated PDGFRα（p-PDGFRα） were detected by Western blotting.RESULTS： SBP in DOCA group and DOCA＋IMA group were signficantly higher than that in control group.No significant difference of SBP between DOCA group and DOCA＋IM group was observed.In DOCA group,severe myocardial fibrosis was found,and CVF and PVCA were higher than those in control group.The differences of the CVF and PVCA between DOCA＋IMA group and control group were detected,but the CVF and PVCA in DOCA＋IMA group were significantly lower than those in DOCA group.Compared with control group,different degrees of myocardial tissue inflammation and monocyte/macrophage infiltration were observed in DOCA group and DOCA＋IMA group.The expression levels of PDGF-A,PDGF-C and PDGFRα in DOCA group and DOCA＋IMA group were much higher than those in control group,but the expression of p-PDGFRα in DOCA＋IMA group were signficantly lower than that in DOCA group.CONCLUSION： Mineralocorticoid-induced myocardial fibrosis is related to cardiac tissue inflammatory response,excessive monocyte/macrophage infiltration and expressions of

关 键 词：伊马替尼 血小板源性生长因子 去氧皮质酮 心肌纤维化 

分 类 号：R542.23[医药卫生—心血管疾病] R363.21[医药卫生—内科学]