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目的探讨死亡受体5(DR5)对神经细胞增殖的影响。方法采用5-溴脱氧尿嘧啶核苷(BrdU)、DR5、Doublecortin(DCX)等抗体免疫荧光标记法,检测各发育阶段(从胚胎期至生后成年,共100只小鼠)脑组织内DR5阳性细胞的表达变化,以及DR5阳性细胞与神经增殖细胞的关系。结果在胚胎期和新生鼠中,DR5阳性细胞密集分布于海马齿状回颗粒细胞层,呈强表达。7日龄(P7)后,DR5阳性细胞减少,强表达的阳性细胞密集分布在齿状回的下颗粒层,其余颗粒细胞呈弱表达。P30后,在齿状回的下颗粒层仅发现少数DR5阳性细胞,其余颗粒细胞不表达DR5。同时,在其他神经细胞增殖区,如新生鼠(P0)小脑外颗粒区和P7嗅球的喙侧迁移流(RMS)区域,DR5阳性细胞的表达和分布规律均表明,DR5阳性细胞是增殖的神经细胞或有丝分裂后期的新生神经元。进一步的实验发现,齿状回下颗粒层的DR5阳性细胞与BrdU阳性细胞或Doublecortin阳性细胞共存,表明DR5阳性细胞是神经前体细胞和新生神经元。结论 DR5阳性细胞是增殖的神经细胞和新生神经元,提示DR5参与神经细胞增殖与分化。
Objective To investigate the effect of death receptor 5 (DR5) on the proliferation of nerve cells. Methods Immunofluorescence staining of antibodies against BrdU, DR5 and Doublecortin (DCX) was used to detect the expression of DR5 in all developmental stages (100 embryos from embryonic age to adult age) Positive cells, as well as the relationship between DR5 positive cells and neural proliferating cells. Results In embryonic and neonatal rats, DR5-positive cells were densely distributed in the hippocampal dentate gyrus granulosa cells with strong expression. After 7 days of age (P7), the number of DR5-positive cells decreased. The strongly positive cells were densely distributed in the lower granular layer of dentate gyrus, and the remaining granulocytes were weakly expressed. After P30, only a few DR5 positive cells were found in the lower layer of dentate gyrus, and the rest of the granulocytes did not express DR5. Meanwhile, the expression and distribution of DR5-positive cells in other neuronal proliferative regions, such as the cerebellar extragalactic granules in neonatal rats (P0) and in the rostral migratory flow (RMS) region of P7 olfactory bulb, indicate that DR5 positive cells are proliferating nerve Cells or late-mitotic neonate neurons. Further experiments showed that DR5-positive cells in the dentate gyrus layer coexisted with BrdU positive cells or Doublecortin positive cells, indicating that DR5 positive cells are neural progenitor cells and neonate neurons. Conclusion DR5-positive cells are proliferating neurons and neonatal neurons, suggesting that DR5 is involved in the proliferation and differentiation of neural cells.