L-精氨酸对阿霉素致大鼠心肌损伤的影响

Effect of L-arginine on cardiac injury induced by adriamycin in rats

目的:从分子水平上研究L-精氨酸(L-argin-ine,L-Arg)对阿霉素(ADM)致大鼠心肌损伤的影响,探讨一氧化氮(nitricoxide,NO)含量增加与超氧化物歧化酶(superoxidedismutase,SOD)、谷胱甘肽过氧化物酶(glutathioneperoxidase,GPx)活性降低的机制。方法:32只SD大鼠随机分成4组(n=8):对照组、L-Arg组、ADM组、ADM+L-Arg组。采用生化方法测定相关分子的含量和酶的活性,采用逆转录聚合酶链反应方法分析相关基因的表达。结果:与ADM组比较,ADM+L-Arg组心肌NO、丙二醛含量明显增加及血清肌酸激酶同功酶MB的活性明显升高(P<0.01),铜锌超氧化物歧化酶(Cu-ZnSOD)mRNA、锰超氧化物歧化酶(MnSOD)mRNA、谷胱甘肽过氧化物酶(GPx)mRNA的表达水平及其酶活性明显降低(P<0.01)。结论:L-Arg加重心肌损伤,机制可能是L-Arg增加ADM处理的大鼠心肌的NO含量,NO抑制Cu-ZnSODmRNA、MnSODmRNA、GPxmRNA表达增加,加重Cu-ZnSOD、MnSOD和GPx活性的降低,致使活性氧增加而损伤心肌。

AIM： From the level of molecule, to study the effect of L-arginine （L-Arg） on cardiac injury induced by adriamycin （ADM） in rats, and to explore the mechanism of increased content of nitric oxide （NO） with reduced activities of superoxide dismutase （SOD） and glutathione peroxidase （GPx）. METHODS： Thirty-two Sprague-Dawley rats were randomly divided into four groups （n = 8, each）： Control group, L-Arg group, ADM treated group and ADM combined with L-Arg group. Using biochemistry technique, we determined the contents of associated substance and activities of enzyme. Reverse transcription-polymerase chain reaction （RT- PCR） was used to analyze the expression of associated gene. RESULTS： Compared with ADM treated group, in ADM combined with L-Arg treated group, contents of malondialdehyde （MDA） and nitric oxide （NO） in myocardium and activity of creatine kinase isoenzymic MB （CKMB） in serum were significantly increased （P 〈 0.01）. However, expressive levels of copper-zinc superoxide dismutase （Cu-Zn SOD） mRNA, manganese superoxide dismutase （Mn SOD） mRNA, GPxmRNA and activities of Mn SOD, Cu-Zn SOD and GPx were significantly reduced （ P 〈 0.01 ）. CONCLUSION： L-Arg intensified cardiac injure. The mechanism may be related to increasing the content of NO in myocardium induced by ADM, and then NO intensified the reduced expressive levels of Mn SOD mRNA, Cu-Zn SOD mRNA and GPx mRNA induced by ADM, thereby intensified the reduced activities of Mn SOD, Cu-Zn SOD and GPx, resulting in intensified cardiac injure caused by the increased reactive oxygen species.