钙调神经磷酸酶信号通路介导大鼠慢性缺氧性右心室心肌肥厚  

Calcineurin Signal Pathway Transduces Right Ventricular Hypertrophy Induced by Chronic Hypoxia in Rats

作　　者：谭建新[1] 陈新民[1] 王优[2] 黄宇戈[2] 

机构地区：[1]南方医科大学福州总医院临床医学部儿科 [2]广东医学院附属医院儿科,广东湛江524001

出　　处：《实用儿科临床杂志》2008年第13期1002-1004,共3页Journal of Applied Clinical Pediatrics

基　　金：广东省自然科学基金项目资助(020566)

摘　　要：目的探讨钙调神经磷酸酶(CaN)信号通路在大鼠慢性缺氧所致右心室心肌肥厚(RVH)中的作用。方法SD大鼠30只随机分为慢性缺氧组、环孢素(CsA)处理组及对照组。慢性缺氧组和CsA处理组大鼠均置缺氧仓内[氧气体积分数为(100±5)mL/L、二氧化碳体积分数<2mL/L]连续缺氧14d,对照组在同一室内常氧条件下饲养。CsA处理组在缺氧同时腹腔注射CsA20mg/(kg·d),慢性缺氧组和对照组注射等量9g/L盐水。实验终点,麻醉大鼠称体质量后快速取出心脏,分离心室并称各部分质量,部分右心室用于检测CaN活性,余右心室置液氮中保存,采用RT-PCR和Western blot法检测相关基因mRNA和蛋白表达。结果慢性缺氧组大鼠右心室与左心室加室间隔质量比[RV/(LV+S)]为0.38±0.04、右心室质量/体质量(RV/BW)为0.75±0.07,均显著高于CsA处理组(0.26±0.03,0.53±0.07)及对照组(0.24±0.03,0.48±0.06)(Pa<0.01);慢性缺氧组右心室心肌β肌球蛋白重链(β-MHC)mRNA、CaN催化亚基A的β亚型(CnAβ)mRNA水平和β-MHC、CnAβ、活化T细胞核因子3(NFAT3)蛋白表达、CaN活性均显著高于CsA处理组及对照组(Pa<0.01),对照组与CsA处理组比较其差异均无统计学意义(Pa>0.05)。结论CaN信号通路在慢性缺氧致大鼠RVH中发挥重要作用,CsA可降低CaN活性,从而抑制慢性缺氧导致的大鼠RVH。Objective To investigate the role of ealeineurin （CaN） signal pathway in the progression of right ventrieular hypertrophy （RVH） induced by chronic hypoxia. Methods Thirty rats were randomly divided into 3 groups：treatment group with cyclosporine （CsA）, chronic hypoxia group and control group. Chronic hypoxia group and treatment group were exposed to normobaric chronic hypoxia[ （ 100 ~ 5 ） mL/L oxygen, less than 2 mL/L carbon dioxide ] for 14 days. Control group was fed in the same room in normal condition. Treatment group was administered simultaneously with CsA[ 20 mg/（ kg · d） ] by intraperitoneal route, and normal saline for chronic group and control group. Right hearts in each group were removed immediately after anesthesia;ventricles were separated and weighted at the end of the experiment. Some right ventricles was used for CaN activity assay and frozen in nitrogen for further Western blot analysis and reverse transcriptase - poly- merase chain reaction （RT - PCR） analysis. Results Fourteen days after hypoxia, right ventricle （RV） to left ventricle （LV） and interventrl- c ular septum weight ratio [ RV/（ LV ± S） ,0.38 ± 0.04 ], RV to body weight （BW） ratio （RV/BW ,0.75 ± 0.07 ） of hypoxia group were higher significantly than those of control group （0.24 ± 0.03,0.48 ± 0.06 ） and treatment group （0.26 ± 0.03,0.53 ± 0.07 ） （ P 〈 0.01 ）. The level of β- myosin heavy chain（ β - MHC ） mRNA and β hypotype of catalytic subunit A of CaN （ CnAβ ） mRNA, the expression of β - MHC, CnAβ and nuclear factor of activated T ceils 3 （ NFAT3 ） , the activity of CaN of right ventrlcular in chronic hypoxia group were all higher significantly than those in treatment group and control group（ P 〈 0.01 ）, which had no significant differences between treatment group and control group（ Po 〉 0.05 ）. Conclusions The CaN signal pathway plays a critical role in the progression of RVH induced by chronic hypoxia. CsA can inhibit RVH by attenuat

关 键 词：钙调神经磷酸酶 信号转导 右心室心肌肥厚 缺氧 

分 类 号：R542.2[医药卫生—心血管疾病]