摘要目的 观察脑源性神经营养因子前体(pmBDNF)对阿尔茨海默病(AD)大鼠模型海马齿状回神经元增殖和分化的影响.方法 成功建立AD大鼠模型后,采用微量渗透泵连续14 d向右侧海马注射proBDNF、羊抗proBDNF抗体或正常羊血清,浓度均为1μg/μl,速度0.5μ/h,同时给予5-溴-2'-脱氧尿核苷(BrdU)50 ms/kg·体重腹腔注射,每日 2次,持续14 d.免疫组化染色并统计新生细胞数量;应用BrdU与微管相关蛋白Doublecortin抗体/抗胶质纤维酸性蛋白抗体免疫三标记法,鉴别BrdU阳性细胞的细胞类型.结果 proBDNF组BrdU阳性细胞数明显低于正常羊血清对照组,而抗proBDNF组则明显高于对照组.proBDNF组、抗proBDNF组以及对照组中各细胞类型的百分比差异无统计学意义.结论 proBDNF能够抑制AD大鼠海马齿状回的细胞增殖,而采用特异性抗proBDNF以拮抗内源性pwBDNF能够促进海马齿状回的细胞增殖,这一功能对于AD的治疗可能有重要的意义.

abstractsObjective To explore the effects of proBDNF on cell proliferation and differentiation in hippocampal dentate gyrus in Alzheimer' disease (AD) rat model. Methods The AD rat model was established. Alzet osmotic minipumps were connected to fight hippocampus of AD rat and filled with pmBDNF, sheep antibody to proBDNF or normal sheep serum respectively. Rats received the injection for 14 days at the speed of 0. 5 μ/h. 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg, ip) was injected twice daily for 14 days. BrdU immunohistochemistry was processed to determine the number of newly generated cells. To examine the phenotype of newly generated cells, immunofluorescent triple labeling was conducted to colocalize BrdU-positive cells with rabbit anti-doublecortine (DCX) or mouse anti-glial fibrillary acid protein (GFAP). Results proBDNF group had fewer BrdU positive cells in dentate gyrus (P ＜ 0. 01 ), while antiproBDNF group had more BrdU positive cells ( P ＜ 0. 01 ) as compared with control group respectively.Immunofluoresent triple labeling showed that there was no phenotypicdifference of BrdU positive cells between each group. Conclusion proBDNF can suppress the proliferation of hippocampal neuron in dentate gyms in AD rats while antiproBDNF has the opposite effect. These findings suggest that promoting the hippocampal neurogenesis by blocking the functions of endogenous proBDNF may be a potential therapeutic strategy for AD.