Roscovitine对C型尼曼-皮克病小鼠球状神经轴突形成的影响  

THE EFFECT OF ROSCOVITINE ON SPHEROID FORMATION IN MICE WITH NIEMANN-PICK DISEASE TYPE C

作　　者：张旻[1] 赵娟[2] 丁志刚[1] 卜碧涛[1] 王伟[1] Inez Vincent 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科 [2]湖北省潜江市江汉油田中心医院神经内科 [3]Department of Pathology,University of Washington,Seattle,Washington,USA98195

出　　处：《中国组织化学与细胞化学杂志》2007年第1期1-5,共5页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金青年基金资助项目(30400141);国家自然科学基金重点项目(30270484)

摘　　要：目的探讨细胞周期依赖性蛋白激酶抑制剂roscovitine对C型尼曼-皮克病(NPC)小鼠(npc-/-)球状神经轴突形成的影响。方法采用不同浓度的roscovitine(72,144,300 and 600nmoles/day)对5.5周龄的npc-/-小鼠进行两周侧脑室灌注,以DMSO灌注的同龄npc-/-小鼠为对照。抗非磷酸化神经细丝蛋白抗体SMI32和抗有丝分裂期磷酸化表位抗体MPM-2免疫染色检测小鼠脑内球状神经轴突的数量,Western blot检测细胞骨架蛋白磷酸化程度的变化。结果Roscovitine组球状神经轴突数量较DMSO组显著减少,神经细丝和tau蛋白的过度磷酸化程度较对照组明显下降(P<0.05)。结论细胞周期依赖性蛋白激酶抑制剂能明显改善NPC的神经元细胞骨架损害。Objective To investigate the effect of cyclin dependent kinase inhibitor roscovitine on spheroid formation in Niemann-Pick disease type C （NPC） mice. Methods Differently concentrated roscovitine （72, 144, 300 and 600nmoles/day） was infused into 5.5 week-old NPC^-/- mice intracerebroventricularly for a 2-week period, using DMSO infused and same aged NPC^-/- mice as controls. Anti-dephosphorylated neurofilament antibody SMI32 and anti-mitotic epitopes antibody MPM-2 were used to count the number of spheroids in different regions of mouse brain by immunohistochemical staining. Western blot was adopted to detect the phosphorylation status of cytoskeletal proteins. Results Compared with DMSO, roscovitine decreased the number of spheroids, attenuated the hyperphosphorylation of neurofilament and tau in brains of NPC mice significantly （P〈0. 05）. Conclusion The cyclin dependent kinase inhibitor can improve the neuronal cytoskeletal lesion in NPC.

关 键 词：细胞周期依赖性蛋白激酶 ROSCOVITINE C型尼曼-皮克病 球状神经轴突 

分 类 号：R322.811[医药卫生—人体解剖和组织胚胎学]