摘要
目的 :探讨钙调神经磷酸酶Aβ(CalcineurinAbeta ,CnAβ)在大鼠慢性缺氧所致右心室心肌肥厚中的作用及抑制CnAβ活性对心肌肥厚的影响。方法 :SD大鼠 18只 ,采用随机分组设计 ,分为缺氧组、环孢菌素A(CsA)处理组及正常对照组。缺氧组、CsA处理组大鼠均置于缺氧仓内连续缺氧 14d ,缺氧第 1天始分别用CsA和生理盐水腹腔注射 ,每天 1次 ,共 14d ,同时与正常组作比较 ,观察缺氧及CsA对大鼠心肌肥厚程度的影响 ,用RT PCR半定量方法分析CnAβmRNA、ANPmRNA、β MHCmRNA、MLC 2mRNA表达的变化。结果 :①缺氧组大鼠右室与左室加室间隔的质量比 [R/(L +S) ]、右室质量 /体质量 (R/BW )高于正常组大鼠 (P <0 .0 1) ,CsA处理后R/(L +S)和R/BW值均低于缺氧组 (P <0 .0 1) ,与正常组大鼠比较差异无显著性意义 ;②缺氧组大鼠CnAβmRNA、ANPmR NA、β MHCmRNA、MLC 2mRNA表达均高于正常组大鼠 (P <0 .0 1) ,CsA处理后CnAβmRNA、ANPmRNA、β MHCmRNA、MLC 2mRNA表达水平均明显低于缺氧组 (P <0 .0 1) ,与正常组比较差异均无显著性意义 (P >0 .0 5 )。结论 :CnAβ参与慢性缺氧性大鼠右心室心肌肥厚 ,抑制CnAβ活性可预防其心肌肥厚 ,本研究为利用CnAβ受体抑制剂治疗心肌肥厚提供了实验依据。
AIM: Cardiac hypertrophy is an adaptive response to various intrinsic and extrinsic stimuli.Calcineurin is a calcium-calmodurin-regulated, serine-threonine phosphatase that functions as a key inducer of stress responsive gene expression through a direct activation of nuclear factor 3 of activated T cells. In cardiomyocytes, calcineurin signaling has been implicated in the regulation of the hypertrophic response caused by pressure overload or neuroendocrine stimulation. Three separatete genes encode the catalytic subunit of calcineurin in mammalian cells, calcineurin Aβ, calcineurin Aα,calcineurin Aγ. This induction of calcineurin activity was associated with an increase in calcineurin Aβ, but not in calcineurin Aα and calcineurin Aγ.In this study, we investigated the role of calcineurin Aβ in the progression of right ventricle cardiac hypertrophy in the chronic hypoxia rats and the effect of calcineurin Aβinhibition on the regression of cardiac hypertrophy. METHODS: 18 SD rats were divided by randomized block design into hypoxia group (n= 6), treatment group with cyclosporine A(n= 6), and normal group(n= 6). The chronic hypoxia model of right ventricle cardiac hypertrophy rats was induced by putting the rats including the hypoxia group and treatment group with cyclosporine A into a hypoxia granary containing 10%±0.5% of O 2 for 14 days. The rats in treatment group were injected cyclosporine A 20 mg/(kg/d) everyday from abdominal cavity for 14 days and the rats of hypoxia group were injected saline. 14 days later killed the rats and measured the R/L+S,R/BW. The calcineurin Aβ mRNA, ANP mRNA,beta-MHC mRNA and MLC-2 mRNA expression were determinated by RT-PCR analysis. RESULTS: ① The R/(L+S), R/BW of hypoxia group all higher than those of normal group(P< 0. 01). The treatment of CsA significantly attenuated these increases, and The R/(L+S),R/BW were no significance when compared with normal group (P>0.05); ②The calcineurin AβmRNA, ANPmRNA, beta-MHCmRNA and MLC-2 mRNA expression of the hypoxia group a
出处
《心脏杂志》
CAS
2004年第6期509-512,共4页
Chinese Heart Journal
