Molecular Biological Study of Cardiomyopathy in animals and in human

去甲肾上腺素(NE)可瞬时诱导即刻早期基因(c-fos mRNA)在金黄地鼠心脏和培养的新生大鼠心肌细胞中表达。注射NE 1.5 mg/kg后，心肌病仓鼠(Bio 14.6)心脏c-fos基因表达较对照仓鼠(Rb)明显增强。静注NE(0.1 mg/kg)后，跑台运动1h可诱导Bio 14.6心脏c-fos基因的表达，而Rb心脏不表达c-fos基因。Bio 14.6心脏与Rb心脏相比，α_1肾上腺素能受体基因表达水平无明显变化。本研究结果提示α1肾上腺素能受体后受体对心肌病仓鼠心脏信号转导通路的增强作用，是应用α1受体阻滞剂治疗心肌病患者的有效方法。我们发现了β-MHC的错义突变(606Val-Gt；Met)，这在几个高加索人肥厚性肉芽肿家系中已有报道。另一种首次在日本发现的突变是外显子3中第10密码子的三个核苷酸的缺失，导致氨基酸甘氨酸的缺失。虽然β-MHC基因分析可以预测肥厚性心肌炎患者的预后，但目前尚无有效的治疗方案，亟待寻找。

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.