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

Role of polyamines in L-arginine inhibiting isoproterenol induced cardiac hypertrophy rat

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）. METItODS： Hypertrophic model of rats was established using ISO. Pretreated 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 N1 - acetyhransferase （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 upregnlated. CONCLUSION ： Exogenous L - arginine inhibits cardiac hypertrophy through downregulating L - arginine/polyamine pathway and upregulating L - arginine/NO pathway.