BMP4参与海人酸损伤后成年大鼠海马齿状回颗粒细胞增殖及胶质增生

Involvement of BMP4 in kainic acid-induced proliferation of granular cells and gliosis in hippocampusl dentate gyrus of adult rats

目的探讨海人酸(KA)侧脑室注射致大鼠海马损伤后骨形成蛋白-4(BMP4)的表达变化及其与颗粒细胞增殖和胶质细胞增生的关系。方法将成年大鼠分为对照组与实验组。侧脑室注射KA7 d后,用尼氏染色检测海马神经元丢失,用免疫组织化学与原位杂交的方法检测海马齿状回BMP4 mRNA阳性细胞与BrdU标记细胞、GFAP阳性细胞数的变化。结果正常成年大鼠BMP4 mRNA阳性细胞主要分布于海马齿状回的门区、颗粒下层、CA3、CA1区。BrdU标记细胞主要分布在齿状回颗粒下层。GFAP阳性细胞主要分布在齿状回、CA3区。在KA侧脑室注射致海马损伤后7 d,海马CA3、CA4区神经元丢失明显,BMP4 mRNA阳性细胞与BrdU、GFAP阳性细胞均明显增加。结论 KA侧脑室注射致海马损伤后,成年大鼠海马齿状回颗粒细胞增殖增强和胶质增生可能与BMP4表达增加有关。

Objective To investigate the changes in the expression of bone morphogenetic protein-4（BMP4） and their relationships with the proliferation of granular cells and gliosis in the injured hippocampus after the intracerebroventricular injection of kainic acid（KA） in adult rat.Methods Adualt rats were divided into the control group and experiment group.The loss of hippocampus neuron was observed by nissl staining after the intracerebroventricular injection of KA.The changes of the BrdU labeled cells,BMP4 mRNA positive cells and GFAP positive cells of the hippocampus denate gyrus were observed by immunohistochemical and hybridization in situ.Results The BMP4 mRNA positive cells were mainly distributed in the hilus and granular layer of dentate gyrus as well as in CA3,CA1 region of the hippocampus in adult rats.The BrdU labeled cells were mainly distributed in the subgranular zone and the GFAP positive cells were mainly in the dentate gyrus and CA3 region.The neuron losses were mainly occurred in CA3,CA4 region and the numbers of BMP4 mRNA positive cells,BrdU labeled cells and GFAP positive cells were increased significantly seven days after the intracerebroventricular injection of KA.Conclusion BMP4 is involved in the proliferation of granular cells and gliosis in adult rat hippocampus after the intracerebroventricular injection of KA.