钙调神经磷酸酶信号通路介导大鼠慢性缺氧致右心室心肌凋亡的机制  

Mechanisms of Calcineurin Signaling Pathway Mediating Myocardium Apoptosis of Right Heart in Rats with Chronic Hypoxia

作　　者：徐小红[1,2] 谭建新[1] 冯华俊[1] 

机构地区：[1]广东医学院附属医院儿科,广东湛江524001 [2]广东省农垦中心医院儿科,广东湛江524002

出　　处：《实用儿科临床杂志》2010年第1期34-37,共4页Journal of Applied Clinical Pediatrics

基　　金：广东省自然科学基金(020566)

摘　　要：目的研究钙调神经磷酸酶(CaN)介导慢性缺氧致右心室心肌凋亡的作用机制。方法SD大鼠30只分为慢性缺氧组、环孢素处理组(CsA,10 mg.kg-1.d-1,腹腔注射)及正常对照组。慢性缺氧组、CsA处理组大鼠均置于缺氧仓内连续缺氧21 d(95～105 mL.L-1O2),正常处理组常温常压常氧饲养21 d。3组大鼠均取右心室,行右心室心肌组织石蜡切片,观察心脏形态学,Western blot及RT-PCR检测各组右心室心肌凋亡指数(AI)、CaNβ亚基(CnAβ)蛋白及mRNA、凋亡蛋白Bcl-2蛋白及mRNA和激活T细胞核因子3(NFAT3)蛋白水平。结果1.缺氧21 d后,CsA处理组大鼠凋亡指数(AI)显著高于慢性缺氧组(P<0.01),且慢性缺氧组AI显著高于正常对照组(P<0.01)。2.慢性缺氧组大鼠右心室心肌CnAβ蛋白及mRNA表达、NFAT3蛋白水平均高于正常对照组及CsA处理组(Pa<0.01)。3.CsA处理组凋亡蛋白Bcl-2蛋白和mRNA表达水平均显著低于慢性缺氧组(Pa<0.01),且慢性缺氧组凋亡蛋白Bcl-2 mRNA表达和蛋白水平也均显著低于正常对照组(Pa<0.05)。结论缺氧可引起大鼠右心室心肌凋亡,CaN可通过CnAβ/NFAT3/Bcl-2信号通路介导抑制慢性缺氧大鼠致右心室心肌凋亡。Objective To investigate ealeineurin signaling pathway which mediates myocardium apoptosis of right heart in rats with chronic hypoxia and the potential mechanisms of it. Methods A rat model of right ventrieular hypertrophy （ RVH ） was established induced by chronic hypoxia（95 - 105 mL · L^-1 O2 ）. Used randomized block design based on different brood,30 rats were divided into 3 groups：treatment group with cyelosporine A （ CsA, 10 mg · kg^-1· d^-1, intraperitoneal injection）, chronic hypoxia group, normal control group （ with normal oxygen）. The rats in CsA treatment group and chronic hypoxia group were exposed to normobaric chronic hypoxia（95 - 105 mL · L^-1O2 ,21 days）. Apoptotic index （AI） , calcineurin Aβ （ CnAβ ） mRNA levels, Bcl - 2 mRNA levels and the protein expression levels of CnAβ, nuclear factor 3 of activated T cells （NFAT3） and Bcl - 2 in right ventricle were investigated. Results 1. The AI of treatment group with CsA was higher than that in chronic hypoxia group（P 〈 0.01 ） and the AI of chronic hypoxia group was higher than that in normal control group（P 〈 0.01 ）. 2. The CnAβ mRNA levels, and the protein levels of CnAβ and NFAT3 of chronic hypoxia group were all significantly higher than those in treatment group with CsA and normal control group （ Pa 〈 0.01 ）. The CnAβ mRNA levels,and the protein levels of CnAβ, NFAT3 ,in right ventricle were all strongly suppressed by CsA （Pa 〈 0.01）. 3. Bcl -2 mRNA and protein level in chronic hypoxia group were higher than those in CsA treatment group （P 〈 0.01 ） ,while Bcl- 2 mRNA and protein level in chronic hypoxia group were lower than those in normal control group （ P, 〈 0.05 ）. Conclusions Chronic hypoxia induces right ventricle apoptosis of rats. Calcineurin can reverse cardiac apoptosis through the signal pathway of CaN/NFAT3/Bcl -2.

关 键 词：钙调神经磷酸酶 信号转导 缺氧 心肌凋亡 环孢菌素 大鼠 

分 类 号：R725.4[医药卫生—儿科]