钙蛋白酶及其抑制剂对心肌肥厚模型大鼠心肌肥厚作用的研究

Myocardial Hypertrophy Process in Rat Model of Myocardial Hypertrophy Mediated by Calpain and Its Inhibitor

目的研究钙蛋白酶calpain及其抑制剂MDL28170与心肌肥厚的关系，探讨心肌肥厚可能的作用机制。方法50只280-350g成年雄性Wistar大鼠随机分为正常对照组（NC组，n=5）、假手术组（SO组，n=5）、手术组（AO组，n=20）、手术＋治疗组（AO＋T组，n=20）。对AO组及AO＋T组大鼠施行腹主动脉缩窄术建立心肌肥厚大鼠模型。4周后行心脏彩超检查。AO＋T组大鼠MDL28170治疗2周后再行心脏彩超检查。取心脏称重，计算心重指数。Westernblot检测心肌中calpainl、calpain2、caNA的表达。结果心脏彩超证实4周后AO组及AO＋T组大鼠心肌肥厚模型建立成功。药物干预后，AO＋T组大鼠心肌肥厚得到控制，进展延缓，与AO组相比差距明显（P〈0．05）。AO组、AO＋T组大鼠心脏质量、心重指数较NC组和S0组增加，AO组增加更明显（均P〈0．05）。与NC组相比，calpainl、calpain2、CaNA表达量在其余3组均有增加；而AO＋T组与AO组比较calpainl、calpain2、CaNA表达量降低（P〈0．05）。结论钙蛋白酶calpain与心肌肥厚关系密切，CaN途径是其作用机制之一；calpain抑制剂MDL28170对实验条件下的心肌肥厚具有明显阻遏作用。

Objective To investigate the relationship between calpain and myocardial hypearophy, and further explore the underlying mecha- nism. Methods A total of 50 adult male Wistar rats （280-350 g） were randomly divided into 4 groups ： normal control group （NC, n = 5）, sham operation group （SO, n = 5 ）, abdominal aortic operation group （AO, n = 20）, abdominal aortic operation plus treatment group （AO＋T, n = 20）. AO group and AO＋T group received the surgery of abdominal aortic coaretation. After 4 weeks, rats of AO＋T group were given MDL28170 for ther- apy for 2 weeks. Then echocardiography examination was performed. The heart mass and calculate the ratio of heart mass and body weight in each group were recorded. The expression of calpainl, calpain2 and CaN A of myocardial tissue were determined by Western blot. Results The myo- cardial hypertrophy model was successfully established in both AO and AO＋T group 4 weeks after operation, as echocardiography indicated. After drug intervention, rats of AO＋T group developed a much slower progress of myocardial hypertrophy and the progressing was under control, which showed a significant gap compared with AO group （P 〈 0.05 ）. The heart mass and the heart mass index （HMI） were increased significantly in AO and AO＋T group than the other two groups, especially in AO group which was more serious （P 〈 0.05）. Compared with NC group, the expression level of calpainl, calpain2, and CaN A were increased in the other 3 groups, while AO＋T group showed a reduced expression by contrast of AO group. The differences between these 2 groups were statistically significant （P 〈 0.05）. Conclusion Calpain is closely related with myocardial hypertrophy, and CaN signaling pathway is one of the most important mechanisms ; calpain inhibitor MDL28170 has an obvious inhibition effect on myocardial hypearophy under the experimental conditions.