川芎嗪对大鼠脑缺血再灌注损伤脑室下区细胞增殖的影响

目的:观察川芎嗪(ligustrazine)对大鼠局灶性脑缺血再灌注损伤侧脑室室下区(subventricular zone,SVZ)细胞增殖的影响.方法:将雄性Sprague-Dawley(SD)大鼠随机分为正常组、假手术组、川芎嗪治疗组和对照组.采用线栓法制作局灶性脑缺血再灌注模型,5-溴脱氧尿嘧啶(5-bromodeoxyuridine,BrdU)标记增殖细胞并用免疫组织化学方法检测BrdU阳性细胞并对SVZ区BrdU阳性细胞计数.采用Western blot检测神经元型一氧化氮合酶(neuro nitric oxide synthase,nNOS)的表达,并测定吸光度值.结果:正常组、假手术组SVZ有少量BrdU阳性细胞,川芎嗪治疗组、对照组SVZ区BrdU阳性细胞再灌注后1 d开始出现,逐渐增加,7 d达到峰值,持续至14 d,在21 d时下降.川芎嗪治疗1 d和3 d组BrdU阳性细胞明显多于对照组(P＜0.01).在缺血对侧SVZ也有细胞增殖,川芎嗪治疗组、对照组在各时间点的变化与缺血侧相似.川芎嗪治疗1 d,3 d组nNOS表达量明显低于对照组(P＜0.05),川芎嗪治疗7 d组与3 d组相比nNOS表达量增加,但与缺血对照组相比无统计学差异.结论:川芎嗪促进局灶性脑缺血再灌注损伤后SVZ区的细胞增殖,其机制可能与nNOS的表达下降有关.

Effect of ligustrazine on cell proliferation in subventricular zone inrat brain with focal cerebral ischemia-reperfusion injury

Objective To observe the effect of ligustrazine on cell proliferation in subventricular zone (SVZ) in rat brain with focal cerebral ischemia reperfusion injury. Methods Male SD rats were randomly divided into a normal group, a sham operation group, a ligustrazine treatment group, and a control group. The ligustrazine treatment group and the control group were further divided into 5 subgroups: 1 d, 3 d, 7 d, 14 d, and 21 d reperfusion after 2 h middle cerebral artery occlusion (MCAO). The focal cerebral ischemia-reperfusion model was made by MCAO. S phase cells were labelled with BrdU. Immunohistochemistry method was conducted to detect the BrdU positive cells. The total number of BrdU positive cells in the SVZ was measured. The expression of neuro nitric oxide synthase (nNOS) was detected with Western blot method. Results There was a significant increase of BrdU positive cells in SVZ of ligustrazine treatment in the 1 d and 3 d group compared with that of the control group (P<0.01). The total number of BrdU positive cells reached a peak in 7 d group and declined afterwards. Cells proliferated also in SVZ on the contralateral side, and peaked at 7 d. The nNOS expression of ligustrazine administration after the focal cerebral ischemia-reperfusion decreased at 1 d and 3 d after the reperfusion compared with that of the control group (P<0.05), and increased at 7 d, but with no significant differnce compared with that of the control group. Conclusion Ligustrazine may promote the cell proliferation in SVZ of adult rats with ischemia-reperfusion injury by decreasing the nNOS expression.