Studies on the cytokines in heart failure

心力衰竭中细胞因子的研究

• 批准号: 05404034
• 负责人: SASAYAMA Shigetake
• 金额: $ 22.14万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05404034/
• 关键词: Cytokine; Myocarditis; Heart failure; Cardiomyopathy; Virus; Interleukin; TNF; PCR; G-CSF; 強心薬; ベスナリノン

This study showed that increased circulating cytokines were detected in patients with acute myocarditis and cardiomyopathy and suggested that cytokines may play some role in the pathogenesis of myocardial injury in these diseases. In our animal model of EMC virus myocarditis, plasma tumor necrosis factor (TNF) -alpha was elevated in the acute stage and exogenously administered anti-TNF-alpha antibody improved survival and myocardial lesion, suggesting importance of TNF-alpha in the pathogenesis. Persistent expression of messenger RNA of TNF-alpha and IL-beta was seen in this model. A recently developed inotropic agent, vesnarinone was effective in the treatment of EMC virus myocarditis by its immunomodulating effect such as inhibition of production of TNF-alpha.Vesnarinone inhibited the production of various cytokines by peripheral blood from patients with heart failure and the reduction of cytokine release may contribute to the beneficial effect of the drug in the treatment of heart failure.

本研究表明，在急性心肌炎和心肌病患者中检测到增加的循环细胞因子，并提示细胞因子可能在这些疾病的心肌损伤的发病机制中起一定作用。在我们的EMC病毒性心肌炎动物模型中，血浆肿瘤坏死因子（TNF）-α在急性期升高，外源性给予抗TNF-α抗体可改善存活率和心肌病变，表明TNF-α在发病机制中的重要性。在该模型中观察到TNF-α和IL-β的信使RNA的持续表达。维司力农是一种新近开发的正性肌力药物，通过其免疫调节作用如抑制TNF-α的产生而有效治疗EMC病毒性心肌炎。维司力农抑制心力衰竭患者外周血中多种细胞因子的产生，减少细胞因子的释放可能有助于药物治疗心力衰竭的有益作用。

项目成果

Kawamoto M et al: "Significance of myocardial upta-ke of iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid:Comparis-on with kinetics of carbon 11-labeledpalmitate in positron emission tomography." J Nucl Cardiol. 1. 522-528 (1994)

Kawamoto M 等人：“碘 123 标记的 β-甲基碘苯基十五烷酸的心肌摄取意义：与正电子发射断层扫描中碳 11 标记的棕榈酸酯的动力学比较。”

Matsumori A et al: "Vesnarinone,a new intropic agent,inhibits cytokine production by stimulated human blood from patients with heart failure." Circulation. 89. 955-958 (1994)

Matsumori A 等人：“Vesnarinone 是一种新型肌力药物，通过刺激心力衰竭患者的人体血液来抑制细胞因子的产生。”

Matsumori A: "Viral infections of the heart:Part II.Animal models:Pathological findings and therapeutic considerations." Edward Arnold, 28 (1993)

松森 A：“心脏病毒感染：第二部分。动物模型：病理结果和治疗考虑。”

Matsumori A: "Idiopathic Dilated Cardiomyopathy:Animal models for therapeutic trials of viral myocarditis.Vesnarinone prolongs survival and reduces lethality in a murine model of lethal endotoxemia." Springer-Verlag, 12 (1993)

Matsumori A：“特发性扩张型心肌病：用于病毒性心肌炎治疗试验的动物模型。维纳里酮可延长致命性内毒素血症小鼠模型的存活率并降低致死率。”

Suzuki H, Matsumori A, Matoba Y, Kyu B, Tanaka A, Fujita J.Sasayama S.: "Enhanced expression of superoxide dismutase messenger RNA in viral myocarditis. An-SH dependent reduction of its expression and myocardial injury." J Clin Invest. 91. 2727-2733 (1993

Suzuki H、Matsumori A、Matoba Y、Kyu B、Tanaka A、Fujita J.Sasayama S.：“病毒性心肌炎中超氧化物歧化酶信使 RNA 的表达增强。An-SH 依赖性减少其表达和心肌损伤。”