蛇毒型神经生长因子对大鼠脑缺血-再灌注损伤后神经前体细胞增殖的影响

Impact of venom nerve growth factor on neural progenitor cell proliferation and migration after cerebral ischemia/reperfusion injury in rats

目的探讨经侧脑室给予蛇毒型神经生长因子(vNGF)对脑缺血-再灌注损伤后大鼠内源性神经前体细胞增殖的影响。方法取健康清洁级雄性Wistar大鼠90只,随机分为2、7、14 d组。每个时间点再分为5个亚组,vNGF25、50、100U组,对照组和假手术组。对照组和vNGF各亚组大鼠建立局灶性脑缺血-再灌注损伤模型,术后各亚组按照规定时间每天经侧脑室埋管给予相应剂量的vNGF或等渗盐水。采用免疫组化法测定各组大鼠缺血皮质周围和海马CA3/齿状回微管相关蛋白(DCX)阳性的神经前体细胞数量。结果①侧脑室给予vNGF后,在各时间点,vNGF各亚组的神经功能Longa评分均低于对照组,差异有统计学意义(P<0.01)。②缺血皮质周围和海马CA3/齿状回1DCX阳性细胞呈现相同的变化趋势。相同vNGF剂量时,7 d亚组的DCX阳性细胞数量高于2 d和14 d亚组,差异有统计学意义(P<0.01)。③相同时间点的不同vNGF剂量亚组比较中,vNGF 50 U亚组的DCX阳性细胞数量高于vNGF 25 U亚组和vNGF100 U亚组,差异有统计学意义(P<0.01)。④在各时间点,vNGF组的DCX阳性细胞数量均高于对照组,差异有统计学意义(P<0.05)。结论经侧脑室给予vNGF后可以增加脑缺血-再灌注损伤后大鼠缺血皮质周围及海马CA3和齿状回DCX阳性的神经前体细胞数量。

Objective To investigate the impact of venom nerve growth factor （vNGF） administered via lateral ventricle on neural progenitor cell proliferation and migration after cerebral ischemia/reperfusion injury in rats. Methods Ninety healthy and clean male Wistar rats were randomly allocated into 2-day, 7-day, and 14-day groups. Then they were redivided into 5 subgroups at each time point： vNGF 25 U, vNGF 50 U, vNGF 100 U, control, and sham operation. The rat focal cerebral ischemia/reperfusion injury models of the control group and each vNGF subgroup were established. Corresponding dose of vNGF or iso- tonic saline was administered via the lateral ventricular eannula in all the subgroups according to the specified time points. Immunohistoehemical method was used to detect the numbers of DCX positive neural precursor cells around the ischemic cortex and hippocampus CA3/Dentate gyrus in rats of each group. Results （1）After administering vNGF via the lateral ventricle at each time point, the Longa＇s scores of the neurological function in all the vNGF subgroups were lower than those in the control group. There were statistical significances （P 〈 0.01 ）. （2）The DCX-positive cells in the peri-ischemic cortex and hippocampus CA3/dentate gyrus showed the same change trend. The numbers of DCX positive cells in the 7-d subgroup was higher than those in the 2- and 14-d subgroups when the vNGF dose was the same. There were statisti- cal signifieances （ P 〈 0.01 ）. （3）In comparison of the subgroups with different vNGF doses at the same time points, the numbers of DCX positive cells in the vNGF 50 U subgroup was higher than those of vNGF 25 U and 100 U subgroups. There were statistical significanees （P 〈 0.01 ）. （4）The numbers of DCX positive eells at each time point in the vNGF subgroups were significantly higher than those in the control group. There were statistical signifieances （P 〈 0.05 ）. Condusion After administering vNGF via the lateral ventricle, it may increase the numbers of DCX positive neural precursor cells in the peri-ischemie cortex and hippoeampus CA3/dentate gyrus after cerebral isehemia/reperfusion injury in rats.