新型氮氧自由基对心脑缺血/再灌注损伤模型大鼠的保护作用研究

目的:研究新型氮氧自由基(N1)对心脑缺血/再灌注(I/R)损伤模型大鼠的保护作用。方法:取大鼠分别建立脑I/R模型和心肌I/R(MI/R)模型,将两种模型大鼠分别分为假手术(0.9%氯化钠注射液)组、模型(0.9%氯化钠注射液)组、阳性对照(传统的氧自由基清除剂Tempol,100 mg/kg)组和高、中、低剂量(N1,100、50、10 mg/kg)组,每组6只,均在建模前腹腔注射相应药物。就脑I/R模型,通过神经功能评分和脑梗死容积百分率评价N1的脑保护功能;就MI/R模型,通过左室收缩压(LVSP)、左室等容收缩/舒张期压力上升或下降最大速率(±dp/dtmax)和血清中肌酸激酶(CK)活性、丙二醛(MDA)的水平评价N1的心脏保护功能。结果:脑I/R模型中,与模型组比较,阳性对照组和各剂量组大鼠神经功能评分均明显增加,脑梗死容积百分率明显减小(P<0.05或P<0.01);与阳性对照组比较,中、高剂量组大鼠脑梗死容积百分率明显减小(P<0.05)。MI/R模型中,与模型组比较,阳性对照组和各剂量组大鼠的LVSP、±dp/dtmax均明显升高(P<0.05或P<0.01),各剂量组大鼠血清中CK活性、MDA水平均明显降低(P<0.05或P<0.01);与阳性对照组比较,高、中剂量组大鼠的LVSP、±dp/dtmax均明显升高(P<0.05或P<0.01),血清中CK活性、MDA水平均明显降低(P<0.05或P<0.01)。结论:N1对大鼠的心脑I/R损伤均具有明显的保护作用,且保护作用强于Tempol。

Protective Effects of New Type Nitroxide Radicals on Myocardial and Cerebral Ischemia-reperfusion Inju- ry Model Rats

OBJECTIVE： To study protective effects of new type nitroxide radicals （N1） on myocardial and cerebral ischemia- reperfusion （I/R） injury model rats. METHODS： Cerebral UR model and myocardial UR model （MI/R） were established respective- ly. 2 kinds of model rats were divided into sham operation group （0.9% Sodium chloride injection）, model group （0.9% Sodium chloride injection）, positive control group （traditional oxyradical scavenger Tempol, 100 mg/kg） and N1 high-dose, medium-dose and low- dose groups （100, 50, 10 mg/kg） with 6 rats in each group. They were given relevant medicine intraperitoneally before modeling. The protective function of N1 in cerebral I/R model was evaluated by neurological function score and the percentage of cerebral infarction volume; in MI/R model, the cardiac protection function of N＇I was measured with the changes of the LVSP, maximum rate of left ventricular isovolumetric systolic/diastolic pressure rising or falling （ ±dp/dtmax）, serum CK activity and MDA level. RESULTS： Compared with cerebral I/R model group, neurological function score of positive control group and N1 groups in- creased significantly, while the percentage of cerebral infraction volume decreased significantly （P〈0.05 or P〈0.01） ; compared with positive control group, the percentage of cerebral infraction volume decreased significantly in N1 high-dose and medium-dose groups （P〈0.05）. Compared with MI/R model group, the levels of LVSP and ±dp/dtmax in positive control group and N1 groups in- creased significantly （P〈0.05 or P〈0.01）, while the serum activity of CK and levels of MDA of N1 groups decreased significant- ly （P〈0.05 or P〈0.01） ; compared with positive control group, the levels of LVSP and ±dp/dtmax in N1 high-dose and medi- um-dose groups increased significantly （P〈0.05 or P〈0.01）, while the serum activity of CK and levels of MDA decreased signifi- cantly （P〈 0.05 or P〈 0.01）. CONCLUSIONS： N1 has obvious protective effects against myocardial and cerebral UR, and is bet- ter than Tempol.