目的 考察注射用丹參多酚酸（SAFI）對腦缺血大鼠急性期用藥的可行性，明確大鼠腦缺血再灌注后腦血流的變化及其與遠(yuǎn)期運(yùn)動(dòng)功能恢復(fù)之間的相關(guān)性。方法 將Wistar大鼠隨機(jī)分為假手術(shù)組、模型組及SAFI （21 mg·kg^-1）組。SAFI組根據(jù)不同給藥時(shí)機(jī)又分為3個(gè)亞組，分別是再灌后立即給藥組（SAFI 0周）、再灌后1周給藥組（SAFI 1周）、再灌后2周給藥組（SAFI 2周），每組每天給藥1次，連續(xù)ip 7 d，為保持一致性，其余時(shí)間均ip生理鹽水，假手術(shù)組及模型組分別ip等量生理鹽水。采用線栓法構(gòu)建大鼠腦缺血再灌注模型，假手術(shù)組僅分離血管。通過觀測大鼠一般狀態(tài)、評估大鼠神經(jīng)功能和腦梗死體積百分比考察SAFI急性期給藥的藥效作用；利用激光多普勒技術(shù)檢測大鼠局部腦血流量（rCBF）；通過轉(zhuǎn)棒實(shí)驗(yàn)和步態(tài)實(shí)驗(yàn)分析大鼠的運(yùn)動(dòng)能力；通過Pearson相關(guān)性分析方法評估不同時(shí)間點(diǎn)的腦血流變化與遠(yuǎn)期運(yùn)動(dòng)功能恢復(fù)之間的相關(guān)性。結(jié)果 與模型組比較，SAFI 0周組大鼠的神經(jīng)功能評分顯著降低（P＜0.01），腦梗死體積百分比顯著降低（P＜0.01），rCBF顯著提升（P＜0.05、0.01），死亡率明顯下降；與模型組比較，SAFI 0周組大鼠在轉(zhuǎn)棒儀上跌落潛伏期顯著增加（P＜0.05、0.01），SAFI 0周組大鼠在步態(tài)儀上運(yùn)動(dòng)速度顯著增加（P＜0.01），四肢的擺動(dòng)時(shí)間、站立時(shí)間和步態(tài)周期顯著下降（P＜0.05、0.01），四肢（除左后肢外）的步幅顯著增加（P＜0.05、0.01）。與SAFI 1、2周組比較，SAFI 0周組腦梗死體積百分比顯著降低（P＜0.01），死亡率降低，rCBF顯著升高（P＜0.05、0.01），明顯促進(jìn)了神經(jīng)行為學(xué)功能及運(yùn)動(dòng)功能的恢復(fù)。Pearson相關(guān)性分析結(jié)果表明腦缺血再灌注損傷后早期的腦血流恢復(fù)與遠(yuǎn)期運(yùn)動(dòng)功能呈線性相關(guān)。結(jié)論 SAFI在缺血急性期給藥具有一定的可行性；腦缺血后梗死周邊區(qū)域血流恢復(fù)對遠(yuǎn)期運(yùn)動(dòng)功能的恢復(fù)至關(guān)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.

R285.5

天津市科技計(jì)劃項(xiàng)目（21YDTPJC00240）；天津市教委科研計(jì)劃項(xiàng)目（2017KJ168）