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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。
Aim To investigate the mechanism of calcineurin (CaN) -mediated apoptosis in right ventricular myocardium induced by chronic hypoxia. Methods Thirty SD rats were divided into chronic hypoxia group, cyclosporine group (CsA, 10 mg.kg-1.d-1, intraperitoneal injection) and normal control group. Rats in both chronic hypoxia and CsA groups were exposed to continuous hypoxia for 21 days (95-105 mL.L-1O2) in the anoxic chamber. The rats in the normal control group were housed for 21 days under normal temperature and atmospheric pressure. The right ventricle and the right ventricular myocardial tissue were paraffin sectioned and the morphology of heart was observed. The myocardial apoptosis index (AI), CaNβ subunit (CnAβ) protein and mRNA were detected by Western blot and RT-PCR. , Apoptosis protein Bcl-2 protein and mRNA and activated T cell nuclear factor 3 (NFAT3) protein levels. After hypoxia for 21 days, the apoptotic index (AI) in CsA-treated rats was significantly higher than that in chronic hypoxia rats (P <0.01), and the AI in chronic hypoxia group was significantly higher than that in normal control rats (P <0.01) . The expression of CnAβprotein and mRNA, NFAT3protein in chronic hypoxia group were higher than those in normal control group and CsA-treated group (Pa0.01). The protein and mRNA expression of Bcl-2 in CsA-treated group were significantly lower than those in chronic hypoxia group (P <0.01), and the expression of Bcl-2 mRNA and protein in chronic hypoxia group were also significantly lower In the normal control group (Pa <0.05). Conclusion Hypoxia can induce right ventricular myocardium apoptosis in rats. CaN can inhibit the apoptosis of right ventricular myocardium induced by chronic hypoxia in rats through CnAβ / NFAT3 / Bcl-2 signaling pathway.