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雷公藤甲素抑制细胞增殖和诱导凋亡对大鼠肺动脉高压的影响

Effects of Triptolide on Antiproliferation and the Enhancement of Apoptosis in Pulmonary Hypertension

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【作者】 魏丽刘童王献民刘斌赵亮周同甫

【Author】 WEI Li LIU Tong WANG Xian-min Department of Children Cardiovascular Diseases,The West China Second Hospital,Sichuan University,Chengdu(610041),Sichuan,China

【机构】 四川大学华西第二附属医院儿科心血管成都市第一人民医院心内科四川大学华西第二附属医院儿科心血管

【摘要】 目的:观察雷公藤甲素对大鼠左肺切除加野百合碱诱导肺血管重构模型的影响并探讨是否与影响细胞增殖和凋亡有关。方法:60只SD大鼠随机分为6组(各组10只):正常组、模型组、连续治疗组、延迟治疗组及(两治疗组)安慰剂对照组。术后5周通过导管插入术测得血液动力学指标,并通过弹力纤维和免疫组织化学染色α-actin、增殖细胞核抗原及caspase-3在光学显微镜下观察肺小动脉的病理学变化。结果:①平均肺动脉压和肌化程度结果显示,模型组与正常组比较,均有极显著性差异(P<0.01);连续治疗组与连续对照组、延迟治疗组与延迟对照组比较,均有显著性差异(P<0.05);连续治疗组与延迟治疗组比较,有显著性差异(P<0.05)。②血管壁细胞增殖度和新生内膜增殖度变化:模型组与正常组比较表达增高,有极显著性差异(P<0.01);连续治疗组与连续对照组、延迟治疗组与延迟对照组比较表达下降,有显著性差异(P<0.05)。Caspase-3染色阳性率结果显示:模型组较正常组表达增高(P<0.05);连续治疗组与连续对照组、延迟治疗组与延迟对照组、延迟治疗组与连续治疗组比较表达增高,有显著性差异(P<0.05~0.01)。结论:雷公藤甲素能延缓大鼠左肺切除加野百合碱注射诱导的肺血管重构,连续和延迟两种治疗方案均有显著的疗效(连续治疗可能更好)。其机制可能与雷公藤甲素的抗增殖效应及增加细胞凋亡作用有关。

【Abstract】 Objective:The study aimed to investigate the therapeutic effects of triptolide on pulmonary vascular remodeling created by open-chest left lung pneumonectomy and following by monocrotaline(MCT)injection.The possible underlying mechanism of anti- proliferation or enhancement of apoptosis was explored. Methods:Sixty spregue dawley rats were divided randomly into 6 groups:Hemodynemie data were collected by catheterization at 5 weeks after procedure and the changes of small pulmonary arteries were evaluated with Von Gienson and immunohistochemi- cal stains to show distribution ofα-actin and PCNA and Caspase-3 on pulmonary arteries. Resuhs:①Compared with normal group,mean pulmonary artery pressure,percentage of muscularization of small pulmonary arteries,and proliferation indexes of smooth muscle cells and neointima proliferation degree were all increased significantly in model Group.②Both continuous and delayed administration prevented the development of pulmonary hypertension in rats,while continuous use seemed more effective.(P<0.05).③Positive rate of caspase-3 staining was observed mainly at the vascular walls when delayed triptolide was administered. Conclusions:In pneumonectomized rats plus MCT injection,both continuous and delayed use of triptolide could suppress the remodeling of pulmonary vasculature.The effects of triptolide was more significant in continuous regimens.Antiproliferation and the promotion of cellular apoptosis may play an important role in facilitating the regression of vascular remodeling.

  • 【文献出处】 中国循环杂志 ,Chinese Circulation Journal , 编辑部邮箱 ,2006年06期
  • 【分类号】R285.5
  • 【被引频次】2
  • 【下载频次】154
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