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尼莫地平对局灶性脑缺血诱导的成年小鼠齿状回神经元再生的影响 被引量：1

Effects of nimodipine on neurogenesis in adult mouse dentate gyrus after focal cerebral ischemia
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摘要 目的　研究L 型电压门控式Ca2+通道(L VGCC)阻断对局灶性脑缺血诱导成年动物海马齿状回神经元再生的影响。方法　成年♂C57 /BL/6小鼠行90min大脑中动脉阻塞(MCAO)手术或者假手术,进行以下三个实验:①手术后48h处死动物,经TTC染色,观察尼莫地平对梗死面积的影响;②手术后5 ~7d,动物经腹腔注射5 溴脱氧尿苷(Br dU),末次注射后24h处死动物,通过免疫组化、Fluoro Jade染色检测尼莫地平对脑缺血诱导的齿状回细胞增殖的作用,并确定细胞增殖是否依赖于海马齿状回细胞的死亡;③动物接受如前所述的BrdU注射,并于末次注射后4wk处死动物,采用免疫荧光双标记观察尼莫地平对脑缺血后新生细胞表型分化的影响。结果　小鼠经过90minMCAO后,齿状回新生神经元数目明显增多,这种缺血诱导的神经元再生并不依赖于齿状回神经细胞的死亡,采用尼莫地平阻断L VGCC则抑制了缺血后的神经元再生。结论　脑缺血后Ca2+经L VGCC内流直接促进缺血诱导的神经元再生。 Aim To explore the effect of blocking L-type voltage-gated Ca^(2+) channel (L-VGCC) on the neurogenesis in adult mouse dentate gyrus after focal cerebral ischemia. Methods Adult male C57/BL/6 mice were subjected to 90 min of MCAO, or sham surgery in three consecutive experiments. ①The animals were killed at 48 h after MCAO, the effect of nimodipine on infarct volume was obversed by TTC staining;②The animals received intraperitoneal injection of BrdU during 5～7 days after 90 min MCAO or sham surgery, and were killed 24 h after the last BrdU injection, the effect of nimidipine on cerebral ischemia-induced cell proliferation and whether the cell proliferation is dependent on the occurrence of cell death in dentate gyrus were determined by immunohistochemistry and Fluoro-Jade staining.③The animals received BrdU as mentioned above and were killed 4 wks after the last BrdU injection, the effect of nimodipine on the phenotypes of BrdU-labeled cells after cerebral ischemia was examined by double immunofluorescence.Results Mice subjected to 90 min of MCAO significantly increased the number of new neurons in the dentate gyrus, which was independent on the occurrence of cell death in dentate gyrus. Blockade of L-type voltage-gated Ca^(2+) channel by nimodipine prevented the neurogenesis in the dentate gyrus after cerebral ischemia.Conclusion This study suggest that Ca^(2+) influx through L-VGCC directly increased ischemia-induced neurogenesis in the adult DG.
作者 罗春霞 张爱霞 王玮 LIU Shuhong 孙婧 朱新建 张书刚 LIU Youming 朱东亚
机构地区 南京医科大学药学院药理学教研室 Dept of Physiology and Biophysics
出处 《中国药理学通报》 CAS CSCD 北大核心 2005年第4期407-412,共6页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目 (No30371640 ) 江苏省自然科学基金资助项目 (No03KJB310083 ) 南京医科大学科技基金资助项目(NoCX2003013)
关键词 局灶性脑缺血 尼莫地平 神经元再生 L-型电压门控式Ca^2+通道 focal cerebral ischemia nimodipine neurogenesis L-type voltage-gated Ca^(2+) channel
分类号 R-332 [医药卫生] R322.81 [医药卫生—人体解剖和组织胚胎学]
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参考文献18

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二级参考文献15

  • 1[1]Jin K, Minami M, Lan JQ et al. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA, 2001;98(8):4710～5
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共引文献4

同被引文献15

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  • 7Kim HY, Moon JS, Lee KS et al. Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates the expression of iNOS through IKK and NF-κB activity in LPS-stimulated mouse peritoneal macrophages an RAW 264.7 cells[J]. Biochem Biophys Res Commun,2004,314:695-703.
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  • 10Kim HY, Moon JS, Lee KS et al. Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates the expression of iNOS through IKK and NF-κB activity in LPS-stimulated mouse peritoneal macrophages an RAW 264.7 cells[J]. Biochem Biophys Res Commun,2004,314:695-703.

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中国药理学通报
2005年 第4期

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