雷诺嗪预处理对大鼠心肌缺血再灌注损伤保护作用的研究

摘要

Objective:To study protective effects of ranolazine preconditioning on myocardial ischemia reperfusion in-jury(MIRI)in rats.Methods:A total of 32 SD rats were randomly and equally divided into sham operation group, ischemia/reperfusion(I/R)group,low dose ranolazine group(low dose group)and high dose ranolazine group (high dose group).HR,SBP,DBP,left ventricular systolic pressure(LVSP),left ventricular diastolic pressure (LVDP),left ventricular pressure maximum rate of rise(+dp/dtmax),left ventricular pressure maximum rate of de-cline(-dp/dtmax),levels of CK-MB,LDH and cTnI,severity of myocardial infarction and ATP concentration were measured and compared among all groups.Results:Compared with sham operation group,there were significant re-ductions in LVSP[(119.35 ± 5.00)mmHg vs.(92.68 ± 2.95)mmHg vs.(100.60 ± 3.12)mmHg vs.(112.22 ± 3.69)mmHg],LVDP[(24.78 ± 1.71)mmHg vs.(17.26 ± 1.69)mmHg vs.(19.25 ± 1.05)mmHg vs.(22.18 ± 1.55)mmHg],+dp/dtmax[(3736 ± 102.37)mmHg/s vs.(3115 ± 112.72)mmHg/s vs.(3338 ± 51.88)mmHg/s vs.(3446 ± 37.99)mmHg/s],-dp/dtmax[(3634 ± 102.51)mmHg/s vs.(3015 ± 127.00)mmHg/s vs.(3239 ±37.36)mmHg/s vs.(3349 ± 45.49)mmHg/s]and ATP concentration[(22.54 ± 1.52)nmol/mg vs.(14.08 ± 1.80) nmol/mg vs.(16.88 ± 0.74)nmol/mg vs.(19.34 ± 0.88)nmol/mg],and significant rise in levels of CK-MB [(490.88 ± 168.04)U/L vs.(1259.0 ± 78.02)U/L vs.(1127.9 ± 127.23)U/L vs.(956.62 ± 105.22)U/L], LDH[(1494.9 ± 174.84)U/L vs.(2657.6 ± 104.33)U/L vs.(2293.9 ± 99.58)U/L vs.(1932.6 ± 134.25)U/L]and cTnI[(1.03 ± 0.14)ng/ml vs.(10.62 ± 1.34)ng/ml vs.(6.97 ± 1.32)ng/ml vs.(4.87 ± 0.79)ng/ml] in I/R group,low dose group and high dose group,P<0.01 all.Compared with I/R group,there were significant rise in LVSP,LVDP,+ dp/dtmax,-dp/dtmaxand ATP concentration,and significant reductions in levels of CK-MB,LDH and cTnI and MI severity[(0.5289 ± 0.0223)vs.(0.4887 ± 0.0089)vs.(0.4438 ± 0.0154)]in low dose group and high dose group(P<0.05 or <0.01),and those of high dose group were significantly better than those of low dose group(P< 0.05 or < 0.01).Conclusion:Ranolazine preconditioning possesses significant protective effect on MIRI,and it's dose-dependent.%目的:研究雷诺嗪预处理对大鼠心肌缺血再灌注损伤(MIRI)的保护作用.方法:将32只SD大鼠随机均分为假手术组、缺血再灌注(I/R)组、低剂量雷诺嗪组(低剂量组)、高剂量雷诺嗪组(高剂量组),测量比较各组HR、SBP、DBP、左室收缩压(LVSP)、左室舒张压(LVDP)、左室内压最大上升速率(+ dp/dtmax)、左室内压最大下降速率(-dp/dtmax)、CK-MB、LDH、cTnI水平、心肌梗死严重程度、三磷酸腺苷(ATP)含量的差异.结果:与假手术组比较,I/R组、低剂量组、高剂量组 LVSP[(119.35 ± 5.00)mmHg比(92.68 ± 2.95) mmHg比(100.60 ± 3.12)mmHg比(112.22 ± 3.69)mmHg]、LVDP[(24.78 ± 1.71)mmHg比(17.26 ± 1.69)mmHg比(19.25 ± 1.05)mmHg比(22.18 ± 1.55)mmHg]、+ dp/dtmax[(3736 ± 102.37)mmHg/s比(3115 ± 112.72)mmHg/s比(3338 ± 51.88)mmHg/s比(3446 ± 37.99)mmHg/s]、-dp/dtmax[(3634 ± 102.51) mmHg/s比(3015 ± 127.00)mmHg/s比(3239 ± 37.36)mmHg/s 比(3349 ± 45.49)mmHg/s]和 ATP 含量[(22.54 ± 1.52)nmol/mg比(14.08 ± 1.80)nmol/mg比(16.88 ± 0.74)nmol/mg比(19.34 ± 0.88)nmol/mg]显著降低,CK-MB[(490.88 ± 168.04)U/L比(1259.0 ± 78.02)U/L比(1127.9 ± 127.23)U/L比(956.62 ± 105.22)U/L]、LDH[(1494.9 ± 174.84)U/L比(2657.6 ± 104.33)U/L比(2293.9 ± 99.58)U/L比(1932.6 ± 134.25)U/L]、cTnI[(1.03 ± 0.14)ng/ml比(10.62 ± 1.34)ng/ml比(6.97 ± 1.32)ng/ml比(4.87 ± 0.79)ng/ml]水平显著升高(P均< 0.01).与 I/R组比较,低剂量组、高剂量组 LVSP、LVDP、+ dp/dtmax、-dp/dtmax和ATP含量显著升高,CK-MB、LDH、cTnI水平和心肌梗死程度[(0.5289 ± 0.0223)比(0.4887 ± 0.0089)比(0.4438 ± 0.0154)]显著降低(P<0.05或< 0.01),且高剂量组显著优于低剂量组(P< 0.05或<0.01).结论:雷诺嗪预处理对心肌缺血再灌注损伤有显著保护作用,且呈剂量依赖性.