川芎嗪对大鼠局灶性脑缺血后侧脑室室下区细胞增殖的作用

目的 观察川芎嗪对大鼠局灶性脑缺血后侧脑室室下区（SVZ）细胞增殖的作用。方法 SD雄性大鼠随机分为假手术组、缺血模型组和川芎嗪组。线栓法制作大鼠大脑中动脉阻塞模型，川芎嗪组术后2h腹腔注射川芎嗪（80mg／kg，1次／d），各组术后4h腹腔注射5-溴脱氧尿核苷（BrdU，50mg／kg，1次／d）。术后7、14、21d取材，采用免疫组织化学染色观察SVZ BrdU阳性细胞数和Doublecortin（DCX）的表达。结果 缺血模型组术后7d时SVZBrdU阳性细胞较假手术组明显增加（P〈0．01），并持续至14d，21d减少；川芎嗪组14dSVZ BrdU阳性细胞达峰值，21d有所减少，与缺血模型组比较，7、14dBrdU阳性细胞均明显增加（P〈0．01）。缺血模型组7d时SVZ有DCX阳性表达，14d达最多，21d表达减少，与假手术组相应时间点比较均明显增加（P〈0．01）；川芎嗪组随缺血时间延长SVZDCX表达明显增强，21d仍处于高水平，与缺血模型组比较，14、21dDCX表达明显增强（P〈0．01）。结论 川芎嗪对成年大鼠局灶性脑缺血诱导的SVZ神经干细胞／祖细胞增殖可能有促进作用。

Effect of Ligustrazine on Cell Proliferation in Subventricular Zone of Lateral Cerebral Ventricle after Adult Rat Suffering from Focal Cerebral Ischemia

Objective To explore the effect of ligustrazine on cell proliferation in subventricular zone of lateral cerebral ventricle after middle cerebral artery occluded (MACO) in adult rat. Methods SD male rats were randomly divided into three group: sham operation group, ischemic model group and Ligustrazine group. The model of the middle cerebral artery occlusion was established by placement of an intraluminal filament at the origin of left MCA. Ligustrazine was administered intraperitoneally with a dose of 80 mg/kg daily starting at 2 hours after MCAO. BrdU (50 mg/kg) was injected once a day intraperitoneally starting at 4 hours after operation. Number of BrdU-positive cells and expression of doublecortin (DCX) in subventricular zone(SVZ) were measured by immunohistochemistry on day 7,14,24 after operation. Results Compared with sham operation group, BrdU-positive cells in ischemic model group increased on day 7, reached the peak on day 14, then decreased on day 21 after operation. On day 7 and 14, the numbers of BrdU-positive cells in Ligustrazine group were markedly augmented and significantly more than those in ischemic model group (P<0.01), but decreased on day 21. The expressions of DCX in SVZ in ischemic model group were enhanced on day 7 with lasting into day 14, and reduced on day 21, but still higher than those in sham operation group on day 7, 14, and 21, respectively. The expressions of DCX in SVZ in Ligustrazine group increased gradually along with prolong of ischemia and kept the high level up to day 21 after operation, and were higher than those in ischemic model group on day 14 and 21. Conclusion Our results suggest that Ligustrazine may promote the cells of SVZ, which the adult rats suffer from the focal cerebral ischemia, to go into cell proliferation.