New development of efficient gene transfer into in vivo myocardium and evaluation of cardiac function after the treatment.
高效基因导入体内心肌及治疗后心功能评估的新进展。
基本信息
- 批准号:12670651
- 负责人:
- 金额:$ 2.5万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2000
- 资助国家:日本
- 起止时间:2000 至 2001
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
At the end-stage of advanced heart failure, cardiac transplantation is a finally available treatment. In the present study, authors have addressed the development of new strategy using gene therapy, based on our preceding studies, employing TO-2 strain hamsters as human DCM model. We prepared reporter gene (Lac Z) or full-length δ-sargoglycan (SG) gene, both of which were driven by CMV promoter and intramurally administered to the apex of the animals under open-chest surgery. The transcript and transgene analyzed by Northern blotting and Western blotting, respectively, revealed both expressions at 10 to 40 weeks later, indicating the appreciable and long-lasting effect of the rAAV vector. Cell-exclusion analysis of Evans blue staining and δ-SG immunostaining denoted that cardiomyocytes after the efficient expression of δ-SG protein demonstrated normalized cell-permeability. Physiological indices measured in vivo by echocardiography and cardiac catheterization also indicated an improved cardiac performances. Finally, Kaplan-Meier's analysis of the animals distinctly certified an improved survival rate in a group cotransfected by Lac Z and δ-SG gene, compared with another group treated by Lac Z alone. These data have provided the first evidence for the effective gene therapy of advanced heart failure and are expected to be applicable for the treatment in human cases in future.
在晚期心力衰竭的终末期,心脏移植是最终可用的治疗方法。在本研究中,作者提出了新的策略,使用基因治疗,在我们以前的研究的基础上,使用TO-2株仓鼠作为人类DCM模型。我们制备了报告基因(Lac Z)或全长δ-sargoglycan(SG)基因,这两种基因都由CMV启动子驱动,并在开胸手术下将其壁内施用于动物的心尖。分别通过北方印迹和西方印迹分析的转录物和转基因揭示了在10至40周后的表达,表明rAAV载体的可感知的和持久的效果。伊文思蓝染色和δ-SG免疫组化细胞排阻分析表明,δ-SG蛋白高效表达后的心肌细胞具有正常的细胞通透性。通过超声心动图和心导管检查测量的体内生理指标也表明心脏性能改善。最后,Kaplan-Meier法分析表明,与单纯Lac Z处理组相比,Lac Z和δ-SG基因共转染组动物的存活率明显提高。这些数据为晚期心力衰竭的有效基因治疗提供了第一个证据,并有望在未来应用于人类病例的治疗。
项目成果
期刊论文数量(36)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Xi H, Shin WS, Suzuki J, et al.: "Dystrophin disruption might be related to myocardial cell apoptosis caused by isoproterenol"J. Cardiovasc. Pharmacol.. 36(Suppl.2). S25-S29 (2000)
Xi H, Shin WS, Suzuki J, et al.:“肌营养不良蛋白破坏可能与异丙肾上腺素引起的心肌细胞凋亡有关”J.
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- 影响因子:0
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Hikiji H,Shin WS et al.: "Peroxynitrite production by TNF-a and IL-1b : implication for suppression of osteoblastic differentiation."Am.J.Physiol.. 278. E1031-E1037 (2000)
Hikiji H,Shin WS 等人:“TNF-a 和 IL-1b 产生的过氧亚硝酸盐:抑制成骨细胞分化的意义。”Am.J.Physiol.. 278. E1031-E1037 (2000)
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Kawada T, Sakamoto A, Nakazawa M, et al.: "Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy"Biochem. Biophys. Res. Commun.. 284. 431-435 (2001)
Kawada T、Sakamoto A、Nakazawa M 等人:“通过体细胞基因治疗对遗传性扩张型心肌病进行形态学和生理学恢复”Biochem。
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- 影响因子:0
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Kawada T, Nakazawa M, Sakamoto A, et al.: "Long-term rescue of hereditrary form of dilated cardiomyopathy by rAAV vector-mediated somatic gene therapy"Proc. Natl. Acad. Sci., USA. 99. 901-906 (2002)
Kawada T、Nakazawa M、Sakamoto A 等人:“通过 rAAV 载体介导的体细胞基因疗法长期挽救遗传性扩张型心肌病”Proc。
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- 影响因子:0
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Kawaguchi H, Shin WS, Okai-Matsuo Y, Nakajima T, Suzuki J, Uehara Y and Toyo-oka T.: "Apoptotic cell death in acute myocardial injury induced by isoproterenol is mediated by nitric oxide"J.Cardiovasc.Pharmacol.. 34. S25-8 (1999)
Kawaguchi H、Shin WS、Okai-Matsuo Y、Nakajima T、Suzuki J、Uehara Y 和 Toyo-oka T.:“异丙肾上腺素诱导的急性心肌损伤中的细胞凋亡是由一氧化氮介导的”J.Cardiovasc.Pharmacol..
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TOYO-OKA Teruhiko其他文献
TOYO-OKA Teruhiko的其他文献
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{{ truncateString('TOYO-OKA Teruhiko', 18)}}的其他基金
Comprehensive strategy for presymptomatic diagnosis of sudden death and heart
猝死与心脏病症状前诊断综合策略
- 批准号:
23590813 - 财政年份:2011
- 资助金额:
$ 2.5万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Preclinical tests for gene therapy of advanced heart failure
晚期心力衰竭基因治疗的临床前试验
- 批准号:
14207033 - 财政年份:2002
- 资助金额:
$ 2.5万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Gene therapy of advanced heart failure
晚期心力衰竭的基因治疗
- 批准号:
10307017 - 财政年份:1998
- 资助金额:
$ 2.5万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Gene diagnoics of Sudden death and its practise
猝死的基因诊断及其实践
- 批准号:
10357004 - 财政年份:1998
- 资助金额:
$ 2.5万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
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