多胺在L-精氨酸抑制异丙肾上腺素诱导的大鼠心肌肥厚中的作用

摘要

目的:研究多胺在L-精氨酸抑制病理性心肌肥厚中的作用及机制.方法:异丙肾上腺素(ISO)皮下注射复制大鼠心肌肥厚模型,L-精氨酸作为干预因素,检测心脏肥大指数,心肌组织胶原染色,心房利钠肽(ANP)的转录水平,观察L-精氨酸对心肌肥大的影响;不同时段,应用高效液相色谱仪(HPLC)测定心肌组织内多胺含量,应用Western blotting结合图像分析系统,检测各组大鼠心肌组织鸟氨酸脱羧酶(ODC)和精眯/精胺乙酰转移酶(SSAT)的蛋白表达水平;检测血清NO含量和NOS活性.结果:皮下注射ISO7d后,心肌肥大指数增加,心肌纤维增粗、排列紊乱,ANP mRNA表达增加;L-精氨酸干预可抑制ISO诱导的心肌肥大,随着L-精氨酸作用时间延长,心肌组织多胺含量减少,血清NOS活性增强,NO含量增加.同时,ODC蛋白表达下调,SSAT蛋白表达上调.结论:L-精氨酸抑制ISO诱导的心肌肥大,其机制可能与下调L-精氨酸/多胺通路、上调L-精氨酸/NO通路有关.%AIM: To explore the role and possible mechanism of polyamine in L - arginine inhibiting cardiac hypertrophy induced by isoproterenol (ISO). METHODS: Hypertrophic model of rats was established using ISO. Pretrea-ted with L - arginine, hypertrophy status of rats was determined by hypertrophy coefficient, collagen content and the expression of ANP mRNA. High performance liquid chromatography ( HPLC) was used to measure the concentrations of polyamines. Western blotting was performed to detect the expressions of ornithine decarboxylase ( ODC) and spermidine/ spermine Nl - acetyltransferase (SSAT). The activity and levels of NOS and NO in serum were also observed. RESULTS : Hypertrophy coefficient and expression of ANP mRNA increased significantly after injection of ISO for 7 d. Moreover, cardiac muscle fibres became thick and disorganized. Pretreated with L - arginine, the above index decreased. Meanwhile , the concentration of polyamine was decreased and plasma NO content and NOS activity were increased, the expression of ODC was downregulated and the expression of SSAT was upregulated. CONCLUSION: Exogenous L - arginine inhibits cardiac hypertrophy through downregulating L - arginine/polyamine pathway and upregulating L - arginine/NO pathway.