川芎嗪-丹参-当归配伍剂与尼莫地平对大鼠脑缺血-再灌注损伤影响的比较

Comparison of the effect of tetramethylpyrazine-salvia miltiorrhiza-angelica sinensis compatibility and nimodipine on cerebral ischemia-reperfusion injury in rats

目的探讨川芎嗪-丹参-当归配伍剂(TSA)对大鼠脑缺血-再灌注损伤的神经保护作用。方法取21只成年雄性Wistar大鼠,应用线栓法制作大鼠右侧大脑中动脉阻塞(MCAO)3 h模型。剔除模型制作过程中死亡的3只大鼠,随机分成3组,TSA组、尼莫地平组和对照组,每组6只。通过尾静脉给药,对大鼠脑缺血-再灌注模型进行干预。分别给予3组大鼠以下药物:川芎嗪(0.35 mg/100 g)+丹参(200mg/100 g)+当归(165 mg/100 g)、尼莫地平(0.1 mg/100 g)和等渗盐水1.5ml。给药时间为再灌注前20min、再灌注后12h和36 h。在MCAO期间和再灌注后48 h,应用脑血流监测仪记录大鼠脑血流量;在再灌注前20min和再灌注后48 h,测评大鼠神经功能缺损评分并计算评分恢复值;再灌注后48 h,TTC染色检测大鼠脑梗死体积。结果 TSA组、尼莫地平组和对照组:①脑血流量变化相对值为(138±44)、(86±18)和(69±8)%;②神经功能评分恢复值为1.3±0.4,1.2±1.0和0.6±0.7;③大鼠脑梗死体积为(144±38)、(344±92)和(382±93)mm^3。TSA组与尼莫地平组比较,所有观测指标差异均具有统计学意义(P<0.01或P<0.05)。结论 TSA提高大鼠脑血流量和减少梗死体积的疗效更佳,对大鼠脑缺血-再灌注损伤的保护作用优于尼莫地平。

Objective To investigate the neuroprotective effect of tetramethylpyrazine-salvia mihiorrhiza-angelica sinensis （TSA） compatibility on cerebral ischemia-reperfusion injury in rats. Methods Twenty-one adult male Wistar rats were recruited and randomly divided into one of the three groups ： TSA, nimodipine and control groups （ n = 6 in each group）. A rat model of right middle cerebral artery occlusion （MCAO） for 3 hours was induced by suture method. The cerebral ischemia-reperfusion rat model was intervened through tail vein injection. The following drugs were given separately to the rats in the three groups： tetramethylpyrazine （0.35 mg/100 g body mass） ＋ salvia miltiorrhiza （200 mg/100 g body mass） ＋ angelica sinensis （ 165 mg/100 g body mass） , nimodipine （0.1 mg/100 g body mass） , and isotonic saline 1.5 mL. The above drugs were given at 20 minutes before reperfusion, 12 and 36 hours after reperfusion. A cerebral blood flow monitor was used to detect and record cerebral blood flow in rats during MCAO and at 48 hours after reperfusion; the neurological scores in rats were evaluated and their recover values were calculated at 20 minutes before reperfusion and 48 hours after reperfusion ; triphenyhetrazolium chloride （TTC） staining was used to detected the volume of cerebral infarction in rats at 48 hours after reperfusion. Results The relative values of the cerebral blood flow changes in the TSA, nimodipine, and control groups were 138±44%, 186±18%, and 69±8% ： the recover values of neurological scores were 1.3±0. 4, 1.2±1.0, and 0. 6±0. 7; and the volumes of cerebral infarction were 144±38 mm^3 , 344±92 mm^3, and 382±93 mm^3 respectively. There were significant differences in all the observation indices between the TSA group and the nimodipine group （P 〈 0.05 or P 〈 0.01 ）. Conclusion The therapeutic efficacy of TSA is more effective in increasing cerebral blood flow and reducing infarct volume of the brain, and its protective effect is superior to nimodipine for cerebral ischemia-reperfusion injury in rats.