注射用丹参多酚酸恢复脑缺血早期血流改善远期运动功能的作用研究

Effect of Salvianolic Acid for Injection on improving long-term motor function by restoring early cerebral ischemia blood flow

目的 考察注射用丹参多酚酸(SAFI)对脑缺血大鼠急性期用药的可行性,明确大鼠脑缺血再灌注后脑血流的变化及其与远期运动功能恢复之间的相关性。方法 将Wistar大鼠随机分为假手术组、模型组及SAFI(21 mg·kg^(-1))组。SAFI组根据不同给药时机又分为3个亚组,分别是再灌后立即给药组(SAFI 0周)、再灌后1周给药组(SAFI 1周)、再灌后2周给药组(SAFI 2周),每组每天给药1次,连续ip 7 d,为保持一致性,其余时间均ip生理盐水,假手术组及模型组分别ip等量生理盐水。采用线栓法构建大鼠脑缺血再灌注模型,假手术组仅分离血管。通过观测大鼠一般状态、评估大鼠神经功能和脑梗死体积百分比考察SAFI急性期给药的药效作用;利用激光多普勒技术检测大鼠局部脑血流量(rCBF);通过转棒实验和步态实验分析大鼠的运动能力;通过Pearson相关性分析方法评估不同时间点的脑血流变化与远期运动功能恢复之间的相关性。结果 与模型组比较,SAFI 0周组大鼠的神经功能评分显著降低(P<0.01),脑梗死体积百分比显著降低(P<0.01),rCBF显著提升(P<0.05、0.01),死亡率明显下降;与模型组比较,SAFI 0周组大鼠在转棒仪上跌落潜伏期显著增加(P<0.05、0.01),SAFI 0周组大鼠在步态仪上运动速度显著增加(P<0.01),四肢的摆动时间、站立时间和步态周期显著下降(P<0.05、0.01),四肢(除左后肢外)的步幅显著增加(P<0.05、0.01)。与SAFI 1、2周组比较,SAFI 0周组脑梗死体积百分比显著降低(P<0.01),死亡率降低,rCBF显著升高(P<0.05、0.01),明显促进了神经行为学功能及运动功能的恢复。Pearson相关性分析结果表明脑缺血再灌注损伤后早期的脑血流恢复与远期运动功能呈线性相关。结论 SAFI在缺血急性期给药具有一定的可行性;脑缺血后梗死周边区域血流恢复对远期运动功能的恢复至关重要。

Objective To investigate the feasibility of Salvianolic Acid for Injection(SAFI)on the acute stage of cerebral ischemia rats,and to clarify the change of cerebral blood flow after cerebral ischemia reperfusion and its correlation with the long-term recovery of motor function in rats.Methods Wistar rats were randomly divided into sham operation group,model group and SAFI(21 mg·kg^(-1))group.The SAFI group was further divided into three subgroups according to the timing of administration,namely,the immediate administration group after reperfusion(SAFI 0 w),the administration group one week after reperfusion(SAFI 1 w),and the administration group two weeks after reperfusion(SAFI 2 w).Each group was given ip once a day for seven consecutive days.To maintain consistency,normal saline was ip for the rest of the time.Sham operation group and model group were treated with the same amount of normal saline.The model of cerebral ischemia reperfusion in rats was established by suture occluded method.In the sham operation group,only blood vessels were isolated.The pharmacodynamic effects of SAFI in acute stage were investigated by observing the general state of rats and evaluating the neurological function and cerebral infarction rate of rats.Regional cerebral blood flow(rCBF)of rats was detected by laser doppler technique.The motor ability of rats was analyzed by rotating rod test and gait test,and the relationship between the changes of cerebral blood flow at different time points and the long-term motor function recovery was evaluated by Pearson correlation analysis method.Results Compared with model group,the neurobehavioral score(P<0.01)and cerebral infarction rate(P<0.01)of rats in SAFI 0 w group decreased significantly,rCBF increased significantly(P<0.05 and 0.01),and mortality decreased significantly.Compared with model group,the drop latency on the rotarod(P<0.05 and 0.01)and the movement speed on the gait meter(P<0.01)of rats in SAFI 0 w group were significantly increased.The duration of swinging time,standing time and gait cycle,and stride length of limbs(except left hind limb)of SAFI 0 w group significantly increased(P<0.05 and 0.01).Compared with SAFI 1 and 2 w group,the percentage of cerebral infarct volume in SAFI 0 w group was significantly decreased(P<0.05 and 0.01),the mortality was decreased,and rCBF was significantly increased(P<0.05 and 0.01),which significantly promoted the recovery of neurobehavioral function and motor function.Pearson correlation analysis showed that there was a linear correlation between early cerebral blood flow recovery and long-term motor function after cerebral ischemia-reperfusion injury.Conclusion SAFI administration in the acute phase of cerebral ischemia has a certain feasibility.Meanwhile,blood flow recovery in the peripheral area of cerebral infarction after cerebral ischemia is crucial to the recovery of cerebral tissue perfusion and long-term motor function recovery.