Studies on the pathogenesis of cardiomyopathy by quantitation of messenger RNA.

通过信使RNA定量研究心肌病的发病机制。

• 批准号: 04454263
• 负责人: MATSUMORI Akira
• 金额: $ 4.29万
• 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 (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454263/
• 关键词: messenger RNA; superoxide dismutase; polymerase chain reaction; virus; cardiomyopathy; free radicals; Captopril; mercapto-propionyl glycine; ポリメラーゼ連鎖反応; フリーラジカル; メルカプトグリシン

In order to investigate the pathogenesis of myocaradial injury in viral myocarditis and subsequent myocardial disorders, we measured quantitatively expression of superoxide dismutase messenger RNA in an animal model of viral myocarditis in which cDNA was synthesized by the polymerase chain reaction.4-wk-old BALB/c mice were inoculated with the encephalomyocarditis virus, and treated with captopril or N, 2-mercapto-propionyl glycine(MPG), a sulfhydryl-containing amino acid derivative without ACE inhibiting property, from days 4 to 14. On day 14, captopril and MPG significantly improved survival of mice and myocardial injury (necrosis, cellular infiltration, and calcification) in a dosedependent manner compared with the infected control group. Thus, captopril and MPG were effective for the treatment of virus-induced myocarditis. Furthermore, a striking induction of manganese superoxide dismutase (Mn-SOD) and copper / zinc SOD (Cu / ZnSOD) when compared with age-matched uninfected mice hearts. MPG completely inhibited the increase of both mRNAs, even when treatment was started on day 4. Thus, oxygen radicals may play an important role in the pathogenesis of viral myocarditis, and a therapeutic approach by eliminating oxygen radicals seems possible.

为探讨病毒性心肌炎及其继发心肌损害的发病机制，采用PCR法合成超氧化物歧化酶（SOD）cDNA，建立病毒性心肌炎动物模型，对4周龄BALB/c小鼠接种脑心肌炎病毒后，给予巯甲丙脯酸（Captopril）或N，2-巯基丙酰甘氨酸（MPG）治疗，不具有ACE抑制性的含巯基氨基酸衍生物，从第4天至第14天。在第14天，与感染对照组相比，Captopril和MPG以剂量依赖性方式显著改善了小鼠的存活率和心肌损伤（坏死、细胞浸润和钙化）。因此，开搏通和MPG对治疗病毒性心肌炎有效。此外，与年龄匹配的未感染小鼠心脏相比，锰超氧化物歧化酶（Mn-SOD）和铜/锌SOD（Cu / ZnSOD）显著诱导。MPG完全抑制两种mRNA的增加，即使在第4天开始治疗时也是如此。因此，氧自由基可能在病毒性心肌炎的发病机制中起重要作用，通过消除氧自由基的治疗方法似乎是可能的。

项目成果

Suzuki H et al: "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 等人：“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。”

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。”

Matsumori A, Kawai C, Yamada T, Ohkusa T, Morishima S, Tamaki N, Watanabe Y, Yonekura Y, Endo K, Konishi J, Yoshida A.: "Mechanism and significance of myocardial uptake of antimyosin antibody in myocarditis and cardiomyopathy : Clinical and experimental s

Matsumori A、Kawai C、Yamada T、Ohkusa T、Morishima S、Tamaki N、Watanabe Y、Yonekura Y、Endo K、Konishi J、Yoshida A.：“心肌炎和心肌病中抗肌球蛋白抗体的心肌摄取的机制和意义：临床

Okada I et al: "Combination treatment with ribavirin and interferon for experimental coxsackievirus B3 replication." J Lab Clin Med. 120. 569-573 (1992)

Okada I 等人：“用利巴韦林和干扰素联合治疗实验性柯萨奇病毒 B3 复制。”

Hosono M, Endo K, Sakahara H, Watanabe Y, Saga T, Nakai T, Kawai C, Matsumori A, Yamada T, Watanabe T, Konishi J.: "Human/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA)." Br J Cancer. 65. 197-200 (1992)

Hosono M、Endo K、Sakahara H、Watanabe Y、Saga T、Nakai T、Kawai C、Matsumori A、Yamada T、Watanabe T、Konishi J.：“人/小鼠嵌合抗体与人抗鼠抗体表现出低反应性（