S-甲基异硫脲对阿霉素致大鼠心肌脂质过氧化的影响  

Effect of S-methylisothiourea on adriamycin induce myocardial lipid peroxidation in rats

作　　者：阳冠明[1] 李树全[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,广西南宁530021 [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》2004年第11期1231-1234,共4页Chinese Pharmacological Bulletin

基　　金：广西教育厅科学基金资助项目 ;No 2 0 0 2 3 16;广西自然科学基金项目 ;No 0 44 70 5 0

摘　　要：目的　研究S 甲基异硫脲 (SMT)对阿霉素 (ADM )所致大鼠心肌脂质过氧化的影响。方法　 32只Wistar大鼠随机分成 4组 :对照组 ;SMT组 (SMT 5 0mg·kg-1,iv ,1次 ) ;ADM组 (ADM 5 0mg·kg-1,ip ,1次 ) ;ADM +SMT组(ADM、SMT的剂量及用法分别同ADM组、SMT组 )。于给药后 2 4h处死所有大鼠。分别用TBA法、硝酸还原酶法、DTNB法、邻苯三酚自氧化法、血红蛋白氧化法测定心肌的脂质过氧化物 (LPO)含量、一氧化氮 (NO)含量、谷胱甘肽过氧化物酶 (GPx)活性、超氧化物歧化酶 (SOD)活性、一氧化氮合酶活性 ;用免疫组织化学法检测心肌的硝基酪氨酸(NT)水平。结果　SMT干预ADM处理的大鼠后 ,降低心肌的LPO及NO含量、诱导型一氧化氮合酶 (iNOS)活性、NT水平 (P <0 0 1) ,增加心肌的SOD及GPx活性 (P <0 0 1)。SMT、ADM对心肌的结构型一氧化氮合酶活性无影响 (P >0 0 5 )。结论　SMT抑制ADM导致心肌脂质过氧化。其机制可能与SMT选择性地抑制ADM所诱导心肌的iNOS活性使心肌产生NO减少而减少心肌生成过氧亚硝基阴离子、保护心肌的SOD及GPx活性有关。Aim To study the effect of S-methylisothiourea(SMT) on adriamy ci n (ADM) induced myocardial lipid peroxidation in rats.Methods T hirty-two Wistar rats were randomly divided into four groups: control group;SMT treated group ( SMT5.0 mg·kg -1,iv,only 1 time);ADM treated group (ADM 5.0 mg·kg -1, ip, only 1 time ); ADM with SMT treated group (the dos ageand method of ADM and SMT were similar to ADM treated group and SMT treated g roup, respectively).24 hour after of administration of the drugs, rats of all t he groups were killed.TBA method, DTNB method, nitrate reductase method, pyrogal lol autoxidation method and hemoglobin-oxidation method were used to determine the contents of lipid peroxide(LPO)and nitric oxide (NO), the activities of glut athione peroxidase (GPx) and superoxide dismutase (SOD) in myocardium, respectiv ely. The level of nitrotyrosine (NT) was determined by immunohistochemical metho d in myocardium.Results SMT significantly reduced the contents of LPO and NO, the activity of inducible nitric oxide synthase (iNOS), the level of NT in myocardium (P<0.01),and significantly increased the activities of SOD and GPx in myocardium, when ADM treated rats were intervened by SMT. The SM T and ADM had no effect on the activity of constitutive nitric oxide synthase in myocardium (P>0.05).Conclusion SMT can inhibit myocardial lipid peroxidation induced by ADM. The mechanism may be that SMT can selective ly inhibited the activity of iNOS in myocardium induced by ADM, reduce productio n of NO in myocardium, thereby reduce production of peroxynitrite and protect the activities of SOD and GPx in myocardium.

关 键 词：S-甲基异硫脲 阿霉素 一氧化氮合酶 一氧化氮 过氧亚硝基阴离子 超氧化物歧化酶 谷胱甘肽过氧化物酶 脂质过氧化物 

分 类 号：R-332[医药卫生] R542.202