瑞舒伐他汀对慢性心力衰竭大鼠的心脏保护作用及其对非对称二甲基精氨酸代谢通路的影响

摘要

目的：探讨瑞舒伐他汀对慢性心力衰竭大鼠的心脏保护作用及其对非对称二甲基精氨酸（ADMA）代谢通路的影响。　　方法：36只SD大鼠，随机分为异丙肾上腺素模型组、瑞舒伐他汀治疗组、正常对照组，每组12只，建立各组模型。检测血清学相关指标和血流动力学参数，并观察心肌组织病理变化，采用免疫印迹方法检测相关蛋白表达的情况。　　结果：与正常对照组比较，异丙肾上腺素模型组脑钠肽、肌钙蛋白I含量、血清ADMA和左心室最大下降速率（-LVdP/dtmin）明显升高（P均<0.01）；左心室收缩压、心率、动脉收缩压、平均动脉压和左心室最大上升速率（+LVdP/dtmax）均显著降低（P均<0.01），差异均有统计学意义。与异丙肾上腺素模型组比较，瑞舒伐他汀治疗组血清脑钠肽、肌钙蛋白I含量、ADMA水平和-LVdP/dtmin明显降低（P均<0.01）；左心室收缩压、心率、动脉收缩压、平均动脉压和+LVdP/dtmax均显著升高（P均<0.01），差异均有统计学意义。与正常对照组相比，异丙肾上腺素模型组蛋白精氨酸甲基转移酶1（PRMT1）的表达增多（P<0.01），二甲基精氨酸二甲胺水解酶2（DDAH2）的表达降低（P<0.01），差异均有统计学意义。与异丙肾上腺素模型组比较，瑞舒伐他汀治疗组PRMT1的表达明显下降（P<0.01），DDAH2表达差异无统计学意义（P>0.05）。　　结论：瑞舒伐他汀对异丙肾上腺素诱导的大鼠慢性心力衰竭心脏具有保护作用，该作用机制与其降低血清肌钙蛋白I、脑钠肽及调控ADMA代谢通路有关。%Objective: To investigate the protection roll of rosuvastatin on chronic heart failure (CHF) in rats with its effect on asymmetric dimethylarginine (ADMA) metabolic pathway. Methods: A total of 36 male SD rats were randomly divided into 3 groups, n=12 in each group. Isoproterenol (ISO) group, the rats received ISO subcutaneous injection (5mg·kg·d) for 7 days to establish CHF model, and then received normal saline gavage administration for 7 days. Rosuvastatin (ROS) treatment group, the rats received ISO with ROS for 7 days, then continuously receiving ROS until 14 days. Normal control group, the rats received saline gavage administration for 7 days. The related serum index and haemodynamic parameters were examined, myocardial pathological changes were observed and the relevant protein expression was measured by Western blot analysis. Results: Compared with Normal control group, ISO group had obviously increased troponin (cTn I), serum ADMA,-LVdP/dtmin, all P<0.01, and decreased left ventricular systolic pressure (LVSP), heart rate, arterial SP, mean arterial pressure, +LVdP/dtmax, all P<0.01. Compared with ISO group, ROS treatment group showed signiifcantly decreased BNP, cTn I, ADMA , -LVdP/dtmin, all P<0.01, and increased LVSP, heart rate, arterial SP, mean arterial pressure,+LVdP/dtmax, all P<0.01. Compared with Normal control group, ISO group had increased expression of protein arginine methyltransferases 1 (PRMT1), decreased expression of dimethyl- arginine dimethylaminohydrolase 2 (DDHA2), both P<0.01. Compared with ISO group, ROS treatment group showed decreased expression of PRMT1, P<0.01 and similar expression DDHA2, P>0.05. Conclusion: Rosuvastatin has the protective roll on ISO induced CHF in rats, which might be related to decreased serum levels of cTn I, BNP and ADMA metabolic pathway regulation.