尼可地尔对心肌肥厚大鼠的保护作用及机制研究

目的:研究KATP通道开放剂尼可地尔(nicorandil,Nic)对甲状腺素诱发的大鼠心肌肥厚的作用。方法:采用大鼠连续10 d,ip,左旋甲状腺素(L-thyroxine,L-thy)造心肌肥厚模型,造模第3天开始Nic灌胃给药,共8 d。观察Nic对大鼠心重指数、组织形态学,心肌线粒体中超氧化物歧化酶(SOD)、丙二醛(MDA)含量及Na -K -ATP酶、Ca2 -ATP酶活力的影响;用免疫组化方法测定Nic对心肌Fas,Bcl-2蛋白表达的影响。结果:与模型组相比,Nic显著降低大鼠的心重指数及改善病理改变,提高心肌线粒体中SOD活性,减少MDA含量,并显著增加Na -K -ATP酶、Ca2 -ATP酶活力;Nic明显抑制肥厚心肌Fas的表达,促进Bel-2的表达。KATP通道的阻滞剂格列苯脲可减弱Nic的上述作用。结论:Nic能显著抑制L-Thy诱发的大鼠心肌肥厚,对肥厚心肌具有明显的保护作用,这可能与Nic通过开放KATP通道从而抑制心肌细胞线粒体脂质过氧化,显著改善能量供应以及减少心肌细胞凋亡等有关。

Protective effects of nicorandil on cardiac hypertrophy in rats and its mechanism

Objective: To assess the effect of ATP-sensitive K channel opener nicorandil on cardiac hypertrophy induced by thyroxine in rats. Method; Cardiac hypertrophy was established by administration of L-thyroxine for 10 days. Nicorandil was administered by gavage to treat the rats for 8 days. Cardiac indexes and morphological changes were examined; the activities of superoxide dismutase (SOD), the content of malondialdehyde ( MDA) , Na -K -ATPase and Ca2 -ATPase in the mitochondria were determined after 8 days of treatment. Expression of Fas and Bcl-2 was studied by the technique of immunohistochemistry. Result: Compared with cardiac hypertrophy group, Nicorandil remarkably reduced the cardiac indexes , improved morphological changes; significantly increased the activities of SOD,Na -K -ATPase, Ca2 -ATPase and decreased the content of MDA in the mitochondria of ventricular myocytes .Nicorandil could obviously reduce the expression of Fas and enhance the expression of Bcl-2. Glibenclamide, a bocker of the ATP-sensitive K channel, could reverse the above effects of nicorandil. Conclusion: Nicorandil could prevent cardiac hypertrophy induced by L-Thy and protect cardiac tissue from injury,which may be related to ameliorating energy metabolism, inhibiting lipid peroxidation and cell apoptosis by opening the ATP-sensitive K channel.