Tan Jian-xin, Liu Chen-zhou, Jie Yu-li, Wang You, Huang Yu-ge
Department of Pediatrics, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524023, China.
Di Yi Jun Yi Da Xue Xue Bao. 2004 Jun;24(6):656-8.
To study the role of calcineurin in the progression of right ventricle myocardial hypertrophy in rats exposed to chronic hypoxia by examining the effect of Ca(2+) channel blockers on the activation of calcineurin and plasma levels of nitric oxide (NO), NO synthase, and endothelin-1 (ET-1).
Rat models of right ventricle myocardial hypertrophy were established by exposing the rats to chronic hypoxia in 10.0%+/-0.5% O(2) for 7 d. The 24 rat models were assigned into normoxic group, hypoxic group and cyclosporin A (CsA)-treated hypoxic group. The rats in normoxic group were kept under normoxic environment, while those in the other 2 groups were subjected to further hypoxic treatment for 14 d, with the rats in CsA group receiving intraperitoneal CsA injection at 20 mg/kg on a daily basis. On day 21 of the experiment, all the rats were killed to collect the hearts for measuring the weight ratio of the right ventricle to the left ventricle and interventricular septum [RV/ LV+S ], as well as the right ventricle to body weight ratio (RV/BW); blood samples were also drawn from the ventricles for measuring plasma NO, iNOS, and ET-1 levels, with the ventricular myocardial Ca(2+) and the activity of calcineurin also determined.
The RV/(LV+S) and RV/BW were significantly higher in hypoxic group than those of the normoxic and CsA groups (P<0.01); the right ventricular myocardial Ca(2+) in CsA group was significantly higher than that in the other two groups (P<0.01). In comparison with the normoxic group, the right ventricular myocardial calcineurin activity was significantly increased in the hypoxic group. CsA treatment significantly suppressed calcineurin activity (P<0.01).
Calcineurin possibly plays a role in the progression of right ventricle myocardial hypertrophy in rats with chronic hypoxia. Blocking L-type Ca(2+) channels with CsA effectively prevents the development of myocardial hypertrophy possibly by inhibiting calcium influx and suppressing calcineurin activity.
通过检测钙通道阻滞剂对钙调神经磷酸酶激活及一氧化氮（NO）、NO合酶和内皮素-1（ET-1）血浆水平的影响，研究钙调神经磷酸酶在慢性缺氧大鼠右心室心肌肥厚进展中的作用。
将大鼠置于10.0%±0.5% O₂的慢性缺氧环境中7天，建立右心室心肌肥厚大鼠模型。将24只大鼠模型分为常氧组、缺氧组和环孢素A（CsA）处理的缺氧组。常氧组大鼠置于常氧环境中，另外两组大鼠继续进行14天的缺氧处理，CsA组大鼠每天腹腔注射20 mg/kg CsA。实验第21天，处死所有大鼠，取心脏测量右心室与左心室及室间隔重量比[RV/(LV+S)]以及右心室与体重比（RV/BW）；同时取心室血样检测血浆NO、诱导型NO合酶（iNOS）和ET-1水平，并测定心室肌细胞内钙离子浓度([Ca²⁺]i)及钙调神经磷酸酶活性。
缺氧组的RV/(LV+S)和RV/BW显著高于常氧组和CsA组（P<0.01）；CsA组右心室心肌[Ca²⁺]i显著高于其他两组（P<0.01）。与常氧组相比，缺氧组右心室心肌钙调神经磷酸酶活性显著升高。CsA处理显著抑制了钙调神经磷酸酶活性（P<0.01）。
钙调神经磷酸酶可能在慢性缺氧大鼠右心室心肌肥厚进展中起作用。CsA通过阻断L型钙通道，抑制钙内流并抑制钙调神经磷酸酶活性，有效预防心肌肥厚的发展。
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