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钙调神经磷酸酶Aβ在缺氧性右心室心肌肥厚中的表达及作用(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2004年第6期
页码:
509-512
栏目:
基础研究
出版日期:
2004-11-01

文章信息/Info

Title:
Calcineurin AβmRNA expression and its role in hypertrophied right ventricle of rats caused by chronic hypoxia
作者:
王　优; 刘郴州; 黄宇戈; 黄秀兰; 谭建新
广东医学院附属医院儿科,广东湛江524001
Author(s):
WANG You ;  LIU Chen-zhou ;  HUANG Yu-ge ;  HUANG Xiu-lan ;  TAN Jian-xin
Department of Pediat rics , Affiliated Hospital of Guangdong Medical College , Zhanjiang , Guangdong 524001 , China
关键词:
钙调神经磷酸酶; 缺氧; 心肌肥厚; 右心室; 环孢菌素A
Keywords:
calcineurin ; hypoxia ; cardiac hypert rophy ; right vent ricle ;  cyclosporine A
分类号:
R542. 2
DOI:
-
文献标识码:
A
摘要:
目的:探讨钙调神经磷酸酶Aβ(Calcineurin A beta ,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14 d ,缺氧第1 天始分别用CsA 和生理盐水腹腔注射,每天1 次,共14 d ,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、ANP mRNA、β-MHC mRNA、MLC-2 mRNA 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. 01) ,CsA 处理后R/ (L + S) 和R/ BW值均低于缺氧组( P < 0. 01) ,与正常组大鼠比较差异无显著性意义; ②缺氧组大鼠CnAβmRNA、ANP mRNA、β-MHC mRNA、MLC-2 mRNA 表达均高于正常组大鼠( P < 0. 01) ,CsA 处理后CnAβmRNA、ANP mRNA、β-MHC mRNA、MLC-2 mRNA 表达水平均明显低于缺氧组( P < 0. 01) ,与正常组比较差异均无显著性意义( P > 0.05) 。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。
Abstract:
AIM: Cardiac hypert rophy is an adaptive response to various int rinsic and ext rinsic stimuli. Calcineurin is a calcium-calmodurin-regulated , serine-threonine phosphatase that functions as a key inducer of st ress 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 hypert rophic 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 Aαand calcineurin Aγ. In this study , we investigated the role of calcineurin Aβin the progression of right vent ricle cardiac hypert rophy in the chronic hypoxia rat s and the effect of calcineurin Aβinhibition on the regression of cardiac hypert rophy. METHODS : 18 SD rat s were divided by randomized block design into hypoxia group ( n = 6) , t reatment group with cyclosporine A( n = 6) , and normal group ( n = 6) . The chronic hypoxia model of right vent ricle cardiac hypert rophy rat s was induced by putting the rat s including the hypoxia group and t reatment group with cyclosporine A into a hypoxia granary containing 10 %±0. 5 %of O2 for 14 days. The rat s in t reatment group were injected cyclosporine A 20 mg/ ( kg/ d) everyday f rom abdominal cavity for 14 days and the rat s of hypoxia group were injected saline. 14 days later killed the rat s and measured the R/ L + S ,R/ BW. The calcineurin AβmRNA , ANP mRNA ,beta-MHC mRNA and MLC-2 mRNA expression were determinated by RT-PCR analysis. RESULTS : ①The R/ (L + S) , R/ BWof hypoxia group all higher than those of normal group ( P < 0. 01) . The t reatment 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 all higher than those of normal group ( P < 0. 01) . The t reatment of CsA significantly decrease these increases , and the calcineurin AβmRNA , ANP mRNA , beta-MHC mRNA and MLC-2 mRNA expression were no significance when compared with normal group ( P > 0. 05) . CONCLUSION:Calcineurin Aβplays a role in the the progression of right vent ricle cardiac hypert rophy in the chronic hypoxia rat s , and the inhibition of calcineurin could reverse cardiac hypert rophy and may play a role in therapying patient s with cardiac hypert rophy.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2004-3-29
更新日期/Last Update: 2004-11-01