1,6-二磷酸果糖对阿霉素导致大鼠心肌酪氨酸硝基化的影响

Effects of fructose-1, 6-diphosphate on adriamycin induce myocardial tyrosine nitration in rats

目的 研究 1,6 二磷酸果糖 (FDP)对阿霉素 (ADM )导致大鼠心肌酪氨酸硝基化的影响。方法 给大鼠腹腔注射ADM(2 5 0mg·kg-1,隔日 1次 ,共 6次 )处理大鼠 ;给ADM处理的大鼠腹腔注射不同剂量的FDP(隔日 1次 ,共2 1次 )进行干预。分别用TBA法、硝酸还原酶法、邻苯三酚自氧化法测定心肌的脂质过氧化物 (LPO)含量、一氧化氮(NO)含量、超氧化物歧化酶 (SOD)活性 ;分别用原位杂交法、免疫组织化学法检测心肌的诱导型一氧化氮合酶 (iN OS)mRNA表达、硝基酪氨酸 (NT) ,半定量分析心肌的iNOSmRNA表达水平、NT水平。结果 FDP(30 0 ,6 0 0 ,12 0 0mg·kg-1)干预ADM处理的大鼠后 ,均可显著降低心肌的LPO及NO含量、显著降低心肌的iNOSmRNA表达水平、显著降低心肌的NT水平、显著增加心肌的SOD活性 (P <0 0 1)。结论 FDP抑制ADM导致心肌酪氨酸硝基化而减轻ADM对心肌的毒性损伤。其机制可能与FDP抑制ADM引起心肌的iNOSmRNA表达而使心肌产生NO减少 ,以及FDP保护心肌的SOD活性而增强心肌清除超氧阴离子的能力 。

AIM To study the effect of fructose 1, 6 diphosphate (FDP) on adriamycin(ADM) induced myocardial tyrosine nitration in rats. METHODS Rats were treated with ADM by intraperitoneal injection (2 50 mg·kg -1 body weight at six times every other day), and then the ADM treated rats were intervened by FDP on different dosages by intraperitoneal injection (at twenty one times every other day). TBA method, nitrate reductase method and pyrogallol autoxidation method were used to determine the content of lipid peroxide (LPO) and nitric oxide (NO), the activity of superoxide dismutase (SOD) of myocardium, respectively. The nitrotyrosine (NT) and expression of inducible nitric oxide synthase (iNOS) mRNA of myocardium was detected by immunohistochemical method and in situ hybridization. The expression level of iNOS mRNA and level of NT in myocardium was semi quantitatively analyzed. RESULTS FDP (300, 600, 1 200 mg· kg -1 ) significantly reduced the content of LPO and NO in myocardium, the expression level of iNOS mRNA and level of NT in myocardium, and significantly increased the activity of SOD in myocardium, when ADM treated rats were intervened by FDP( P <0 01). CONCLUSION FDP can inhibit myocardial tyrosine nitration induced by ADM, and thereby reduce injury of cardiotoxicity induced by ADM. The mechanism may be relate to FDP inhibit expression of iNOS mRNA in myocardium induced by ADM, reduce to produce NO in myocardium, and it protect the activity of SOD in myocardium, enhance capability of scavenge superoxide anion in myocardium, thereby reducing to produce peroxynitrite in myocardium.