CAJ | 학술논문

本工作在大体动物模型、细胞及分子水平上，对钙调神经磷酸酶(CaN)依赖的信号通路在大鼠心肌肥大中的作用及其调节机制进行了研究。结果发现：(1)CaN信号通路参与血流动力学超负荷、心肌纤维化、旁／自分泌因子等诱导的心肌细胞肥大；(2)CaN信号通路参与血管紧张素Ⅱ(AngⅡ)及碱性成纤维细胞因子(bFGF) 诱导的心肌细胞肥大和AngII及bFGF刺激的心脏成纤维细胞增殖；（3) CaN通路与丝裂素活化蛋白激酶(MAPK)及蛋白激酶C(PKC)信号途径可能存在相互联系；（4)CaN的活化依赖胞内Ca 2+浓度的持续升高，CaN的活化还受蛋白激酶磷酸化的调节；AngⅡ刺激心肌细胞CaN mRNA 的表达显著增加，CaN mRNA 本身的表达受Ca2+信号及MAPK级联反应的调控。结论：C a2+-CaN信号通路介导心肌肥大的发生。
본공작재대체동물모형、세포급분 자수평상， 대개조신경린산매(CaN)의뢰적신호통로재대서심기비대중적작용급기조절궤제진행료연구 。결과발현：(1)CaN신호통로삼여혈류동역학초부하、심기섬유화、방／자분비인자등유도 적심기세포비대；(2)CaN신호통로삼여혈관긴장소Ⅱ(AngⅡ)급감성성섬유세포인자(bFGF) 유 도적심기세포비대화AngII급bFGF자격적심장성섬유세포증식；（3) CaN통로여사렬소활화 단백격매(MAPK)급단백격매C(PKC)신호도경가능존재상호련계；（4)CaN적활화의뢰포내Ca 2+농도적지속승고，CaN적활화환수단백격매린산화적조절；AngⅡ자격심기세포CaN mRNA 적표체현저증가，CaN mRNA 본신적표체수Ca2+신호급MAPK급련반응적조공。결론：C a2+-CaN신호통로개도심기비대적발생。
The present study investigated the role and regulation of calcine urin-dependent signal pathway in cardiac hypertrophy of rats from the three le ve ls of animal model, culturing cells and molecular biology.The results showed as follows: （1)Calcineurin signal pathway involves in myocyte hypertrophy induced by various factors such as hemodynamic overload, myocardial fibrosis, paracrine/ a utocrine factors, etc.; (2) Calcineurin-dependent signal pathway plays an im p ortant role not only in AngⅡ- and bFGF-induced cardiac myocyte hypertrophy bu t also in AngⅡ- and bFGF-stimulated cardiac fibroblast proliferation.(3)Calci n eurin pathway may associate with MAPK and PKC pathways at several levels; (4)Act i vation of calcineurin depends on sustained increase of intracellular calcium con centration and is regulated by protein phosphorylation. The expression of calcin eurin gene in AngⅡ-stimulated myocytes might be regulated by Ca2+ signal and MAPK cascade. In conclusion, Ca2+-calcineurin signal pathway involv es in the development of cardiac hypertrophy of rats.