摘要
目的探讨阿魏酸钠预处理对离体大鼠心脏缺血/再灌注损伤的保护作用及相关机制。方法56只SD大鼠随机分为7组(每8只):正常对照(Cont)组;缺血损伤(I/R)组;缺血预适应(IP)组;阿魏酸钠(SF)组;左旋精氨酸甲基酯(L-NAME)组;格列本脲(Glib)组;NAME+Glib组。采用离体大鼠心脏Langendorff逆行灌注模型,观察各组心脏缺血再灌注前后心功能指标以及超氧化物岐化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)和鸟苷环磷酸(cGMP)含量的变化。结果阿魏酸钠或IP组与I/R组相比较,可明显改善I/R后的心功能,表现为心室肌收缩功能增强、左心室最大收缩压(LVSP)提高、心律失常发生率减少(P<0·01)。心室肌组织NO含量和cGMP浓度明显较高(P<0·01);阿魏酸钠组与IP组之间,上述指标无统计学差异(P>0·05)。而阿魏酸钠与L-NAME和/或Glib一起预灌后,其心肌保护作用被明显减弱(P<0·01)。结论阿魏酸钠预处理能增加NO的产生和释放,拮抗氧自由基,减轻心肌I/R损伤;提示通过NO激活cGMP-PKC途径使ATP敏感钾通道开放可能是阿魏酸钠预适应保护的重要机制。
Objective To investigate the cardioprotective effects of sodium ferulate （SF） mediated by nitric oxide on ischemia-reperfusion injured myocardium. Methods Fifty-six SD rats were killed. Their hearts were isolated and randomly divided into 7 equal groups ： ischemia/reperfusion group （ I/R group ）, ischemic/preconditioning （IP group, to be perfumed with anoxic and reoxygenated fluid several times so as to produce protection against continuous and severe ischemia）, SF pretreatment group （to be perfused with fluid with SF and then made I/R model）, L-NAME ＋ SF group （ to be perfused with fluid with SF and L-NAME, a NO inhibitor, and then made I/R model） , glibenclamide （Glib） ＋ SF group （to be perfused with Glib ＋ SF and then made I/R model ）） , L-NAME ＋ Glib ＋ SF group （to be perfused with L-NAME ＋ Glib ＋ SF and then made I/R model ））, and control group （normal isolated hearts ）. Electrocardiography was conducted and left ventricular systolic pressure （LVSP） , dp/dtmax, and heart rate （HR） were measured. By the end of the experiment 0.5 grams of tissue was taken from the left ventricle. The levels of superoxide dismutase （SOD）, malonyldialdehyde （MOD）, NO, and cyclic guanosine monophophate （cGMP） were detected. Results The levels of LVSP, dp/dtmax, and HR of the SF pretreatment group and IP group were all significantly higher than those of the I/R group （ all P 〈 0.01 ） without significant differences between these 2 groups （ all P 〉 0.05 ）. The levels of LVSP, dp/dtmax, and HR of the L-NAME, Glib ＋ SF, and L- NAME ＋ Glib ＋ SF groups were all significantly lower than those of the SF pretreatment group and IP group （ all P 〈 0.01 ）. Ventricular extrasystole （VE） and ventricular tachycardia （VT） during re-perfusion period occurred in all hearts of the I/R group, however, the incidence rates of VE and VT of the IP and SF groups were all significantly lower than those of the I/R group （ all P 〈 0.01 ） , however, without significant differences between the IP and SF groups （ all P 〉 0.05 ）. The incidence rate of VE and VT of the L-NAME, Glib ＋ SF, and L-NAME ＋ Glib ＋ SF groups were all significantly higher than those of the SF group （ all P 〈0.01 ）. The myocardium MDA content of the I/R group was significantly higher and the SOD activity significantly lower in comparison with the control group （both P 〈 0.01 ） ; the myocardium MDA contents of the IP and SF groups were significantly lower and the SOD activity levels significantly higher in comparison with the I/R group （all P 〈0.01 ）, however, with significant differences between theses 2 groups （both P 〉 0.05） ; the myocardium MDA contents were significantly higher and the SOD activity levels significantly lower in the L-NAME, Glib ＋ SF, and L-NAME ＋ Glib ＋ SF groups in comparison with the SF and IP groups （all P 〈0.01 ）. The myocardium NO2^-/NO3^- and cGMP contents of the I/R group were both significantly lower than those of the control group （ both P 〈 0.01 ）, and the myocardium NO2^-/NO3^- and cGMP contents of the IP and SF groups were both significantly higher than those of the I/R group （ both P 〈 0. 01 ）, however, without significant differences between these 2 groups （ both P 〉 0.05 ）. The myocardium NO2^- / NO3^- and cGMP contents of the L-NAME, Glib ＋ SF, and L-NAME ＋ Glib ＋ SF groups were all significantly lower than those of the SF group （ all P 〈 0.01 ）. Conclusion SF pretreatment significantly improves the releasing of NO, decreases oxygen free radicals, and relieves myocardial ischemia reperfusion injury. The opening of the ATP-sensitive potassium channels induced by the cGMP way of NO activation may be an important pathway in the cardioprotective effects of SF pretreatment.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2006年第14期987-991,共5页
National Medical Journal of China
基金
江西省科技厅基金资助项目
教育厅基金资助项目
卫生厅中医处科研基金资助项目
关键词
阿魏酸
再灌注损伤
一氧化氮
鸟苷环磷酸
K^+-ATP通道
Sodium-ferulate
Reperfusion injury
Nitric oxide
Guanosine 3＇, 5＇-cyclic monophosphate
K^＋-ATP channel
