Molecular Biological Study of Cardiomyopathy in animals and in human

用去甲肾上腺素（NE）处理仓鼠在体心脏和培养的新生大鼠心肌细胞，瞬时诱导即刻早期基因（c-fos mRNA）的表达。注射NE 1.5mg/kg后，心肌病仓鼠（Bio 14.6）心脏c-fos mRNA表达较对照仓鼠（RB）明显增强。NE（0.1mg/kg）注射后跑台1小时可诱导Bio 14.6心脏c-fos mRNA表达，而RB心脏无c-fos mRNA表达。Bio 14.6心脏α_1肾上腺素能受体mRNA水平与RB心脏相比无明显升高。本研究分析了日本家族性肥厚型心肌病（Familial Hypertrophic Cardiomyopathy，HCM）患者的β-肌球蛋白重链（beta-myosin heavy chain，β-MHC）基因。我们发现了一个在多个高加索HCM家系中报道的β-MHC错义突变（606Val-> Met）。另一种突变是第3外显子第10位密码子的3个核苷酸缺失，导致氨基酸甘氨酸的缺失，这是首次在日本人中发现。虽然β-MHC基因的分析可以预测HCM患者的预后，但目前还没有有效的治疗方案，这是人们迫切需要的。

The expression of immediate early gene (c-fos mRNA) was transiently induced after norepinephirine (NE) treatment in hamster hearts in vivo as well as in cultured neonatal rat myocytes. The expression of c-fos mRNA in the heart was more augmented in cardiomyopathic hamster(Bio 14.6) than in control hamster (RB) after 1.5 mg/kg of NE injection. Treadmill running for 1 hr after NE(0.1mg/kg) injection induced the expression of c-fos mRNA in the Bio 14.6 heart but not in RB heart. The mRNA level of alpha_1 adrenergic receptor was not increased in Bio 14.6 heart compared to that of RB heart. The present results suggest that the post-receptor enhancement of signal transduction pathway after alpha_1 adrenergic receptor in cardiomyopathic hamster heart, and the profitable management for cardiomyopathic patients with alpha_1 blocking agents.The cardiac beta-myosin heavy chain (beta-MHC) gene was analyzed in Japanese patients with familial hypertrophic cardiomyopathy(HCM). We found missence mutation (606Val -> Met) of beta-MHC, which has been reported in several Caucasian HCM families. Another kind of mutation, found in Japanese for the first time, was the deletion of three nucleotides of 10th codon in the exon 3, which results in the delection of an amino acid, glycine. Although the analysis of beta-MHC gene could lead to the predicition of prognosis of the patients with HCM, we don't have effective therapy regimen yet, which is eagerly hunting for.