摘要
目的:探讨硝酸异山梨酯(ISDN)能否诱导大鼠后期预适应及其可能机制。方法:采用大鼠在体缺血再灌注(I/R)模型,将动物随机分为生理盐水组、ISDN给药组、假手术组、后期缺血预适应组、生理盐水+I/R组、ISDN+I/R组、生理盐水+格列苯脲+I/R组、ISDN+格列苯脲+I/R组。前两组于给药24h后,测定心肌组织中的SOD和诱导型一氧化氮合成酶的含量,含I/R组于给药24h后进行缺血40min再灌注1.5h后测心肌梗死范围、心肌组织及血清学指标。结果:ISDN组心肌组织中诱导型一氧化氮合成酶浓度明显比生理盐水组高(P<0.01);后期缺血预适应组和ISDN+I/R组与生理盐水+I/R组相比,心肌梗死面积、血清肌酸激酶和乳酸脱氢酶含量明显减少(前两者P<0.05,后者P<0.01),心肌组织中NO和锰-SOD显著增加,丙二醛显著下降(P<0.05)。结论:ISDN能诱导心肌后期预适应,其机制与NO和诱导型一氧化氮合成酶的升高以及机体的抗氧化能力增强有关。
AIM： To determine whether isosorbide dinitrate（ISDN） could induce late ischemic preconditioning in rots. MIETHODS： SD rats were divided into oral normal saline （control group ）, oral ISDN （0.2 mg·kg^-1, ISDN group）, SHAM group; oral normal saline combined with ischemia and reperfusion （I/R） （I/R control group）, ISDN plus I/R group, ISDN plus Gly plus UR group, Gly plus I/R control group and late ischemic preconditioning group （3 cycles of 5-min coronary occlusion/5-min reperfusion, LPC group）. 24 h later, rats, like other groups with I/R, were underwent a 40 rain coronary occlusion followed by 1.5 h of reperfusion. RESULTS： Myocardial infarct size and the levels of creatine kinase （CK） in serum were significantly reduced after pretreated with ISDN ＋ I/R versus I/R control group （ P 〈 0.05）, so was lactate dehydrogenase （LDH） （ P 〈 0.01）. Nitric oxide and Mn-supemxide dismutase in heart tissue were significantly elevated, while MDA was significantly reduced （ P 〈 0.05 ）. The level of induced nitric oxide synthetase （iNOS） in heart tissue was significantly elevated in the ISDN group compared with controls （P 〈 0.01 ）. CONCLUSION： ISDN induces delayed cardioprotection against myocardial infarction similar to that afforded by the late phase of ischemic PC, possibly by up-regulating NO and iNOS, and strengthening antioxidant mechanism.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第12期1385-1388,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
