β-胡萝卜素对阿霉素致大鼠心肌组织的超氧化物歧化酶、谷胱甘肽过氧化物酶mRNA表达改变的影响  

Effect of beta-carotene on adriamycin induced changes of expression of mRNA of superoxide dismutase and glutathione peroxidase in myocardial tissue of rats

作　　者：阳冠明[1] 孙胜涛[1] 李树全[1] 林伟雄[1] 刘微[1] 叶司原 利基林 林善修[1] 

机构地区：[1]广西医科大学第一附属医院儿科 [2]广西肿瘤研究所生化室,广西南宁530021

出　　处：《中国药理学通报》2006年第4期465-470,共6页Chinese Pharmacological Bulletin

基　　金：广西教育厅科学基金资助项目(No2002-316);广西自然科学基金资助项目(No0447050)

摘　　要：目的研究β-胡萝卜素(BC)对阿霉素(ADM)所致大鼠心肌组织的锰超氧化物歧化酶(Mn SOD)mRNA、铜-锌超氧化物歧化酶(Cu-Zn SOD)mRNA、谷胱甘肽过氧化物酶(GPx)mRNA表达改变的影响,探讨BC拮抗ADM导致心肌组织的Mn SOD、Cu-Zn SOD、GPx活性降低的机制。方法大鼠腹腔注射(ip)ADM(10·0mg·kg-1,1次);ADM处理的大鼠灌胃(ig)不同剂量的BC(每天1次,3次;ipADM前igBC,每天1次,11次行预处理)进行干预。分别用硫代巴比妥酸法、硝酸还原酶法、黄嘌呤氧化酶法、二硫代二硝基苯甲酸法、血红蛋白氧化法测定心肌组织的丙二醛(MDA)含量、一氧化氮(NO)含量、Mn SOD及Cu-Zn SOD活性、GPx活性、一氧化氮合酶活性;RT-PCR方法检测心肌组织的Mn SODmRNA、Cu-Zn SOD mRNA、GPx mRNA、诱导型一氧化氮合酶(iNOS)mRNA表达。结果BC(20·0,40·0,80·0mg·kg-1)拮抗ADM所致心肌组织的MDA含量及NO含量增加、iNOS mRNA表达水平增加及其酶活性增加(P<0·01);拮抗ADM所致心肌组织的Mn SOD mRNA、Cu-Zn SOD mR-NA、GPx mRNA表达水平降低及其酶活性降低(P<0·01)。结论BC拮抗ADM导致心肌组织的Mn SOD mRNA、Cu-ZnSOD mRNA、GPx mRNA表达降低而拮抗ADM导致Mn SOD、Cu-Zn SOD、GPx活性降低。其机制可能与BC抑制ADM诱导心肌组织的iNOS mRNA表达而降低iNOS活性使心肌组织产生NO减少,从而减少NO抑制Mn SOD mRNA、Cu-ZnSOD mRNA、GPx mRNA表达有关。Aim To study the effect of beta-carotene （BC） on adriamycin （ADM） induced changes of expression of manganese superoxide dismutase （Mn SOD） mRNA, copper-zinc superoxide dismutase （Cu-Zn SOD ） mRNA and glutathione peroxidase （GPx） mRNA in myocardial tissue of rats, and to explore the mechanism of BC antagonized to the reduced activities of Mn SOD, Cu-Zn SOD and GPx in myocardial tissue induced by ADM. Methods Rats were treated with ADM by intraperitoneal injection （ ip, 10. 0 mg · kg^-1 body weight, only 1 time） , and then the ADM treated rats were intervened by BC at different dosage by intragastric perfusion （every day for 14 times , ADM was administered by ip at 12 days ）. Thiobarbituric acid method, nitrate reductase method, xanthine oxidase method, 5,5＇-dithiobis-（2-nitrobenzoic acid） method and hemoglobin-oxidation method were used to determine the contents of malondialdehyde （MDA） and nitric oxide（NO） , the activities of Mn SOD, Cu-Zn SOD , GPx and nitric oxide synthase in myocardial tissue, respectively. The expression of Mn SOD mRNA, Cu- Zn SOD mRNA, GPx mRNA and inducible nitric oxide synthase（iNOS） mRNA were detected by reverse transcription- polymerase chain reaction method in myocardial tissue. Results BC （ 20. 0,40. 0,80. 0 mg · kg^-1） has antagonistic effect on increasing the contents of MDA and NO, the expressive level of iNOS mRNA, the activiy of iNOS, and reducing the expressive levels of Mn SOD mRNA, Cu-Zn SOD mRNA and GPx mRNA, and reducing the activities of Mn SOD, Cu-Zn SOD and GPx in myocardial tissue induced by ADM（ P 〈 0. 01 ）. Conehmion BC antagonized the reduced expression of Mn SOD mRNA, Cu-Zn SOD mRNA and GPx mRNA in myocardial tissue induced by ADM, thereby antagonized the reduced activities of Mn SOD, Cu-Zn SOD and GPx in myocardial tissue induced by ADM. The mechanism may be related to BC inhibited ADM induced the expression of iNOS mRNA in myocardial tissue , thereby reduced the activity of iNOS , and reduced the generation o

关 键 词：Β-胡萝卜素 阿霉素 超氧化物歧化酶 谷胱甘肽过氧化物酶 一氧化氮合酶 一氧化氮 基因表达 

分 类 号：R-332[医药卫生] R282.71