Noggin参与海人酸损伤后成年大鼠海马颗粒下区颗粒细胞增殖

Noggin participates in dentate gyrus subgranular zone granular cell proliferation following kainic acid-induced hippocampal injury in rats

目的探讨侧脑室注射海人酸（KA）致大鼠海马损伤后Noggin的表达变化及其与颗粒细胞增殖的关系。方法健康雄性SD大鼠32只采用随机数字表法分为实验组（16只）及对照组（16只），对照组义分为生理盐水对照组和空白对照组，各8只。实验组大鼠侧脑室注射KA，生理盐水对照组注射等剂量生理盐水，空白对照组不作处理。侧脑室注射KA 1周内，尼氏染色检测海马神经元的丢失，免疫荧光染色与原位杂交的方法检测海马齿状回BrdU标记细胞与Noggin mRNA阳性细胞的变化。结果在侧脑室注射KA致海马损伤后1周，海马CA3、CA4区神经元丢失明显。与生理盐水对照组比较，实验组海马齿状同BrdU阳性细胞升高，差异有统计学意义（P=0．006），其中注射侧较对侧更为明显。海马Noggin mRNA阳性细胞在第3天时升高，第7天时下降。结论侧脑室注射KA致海马损伤后．成年大鼠海马齿状回颗粒细胞异常增殖可能与Noggin表达波动有关。

Objective To investigate the relation between noggin expression changes and granular cell proliferation in the dentate gyrus subgranular zone （DG-SGZ） in rats with kainic acid （KA） -induced hippocampal injury. Methods Thirty-two adult male SD rats were randomly assigned into KA injury group （n=16） for intracerebroventricular KA injection and control group （n=16） which received intracerebroventricular normal saline injection （n=8） or no treatment （n=8）. Nissl staining was used to assess the cell loss in the hippocampus, and in situ hybridization and immunofluorescence staining was used to detect noggin expression and BrdU-labeled cells in the DG-SGZ. Results The BrdU-labeled cells were found mainly in the DG-SGZ, and noggin mRNA-positive cells mainly in the hilus, DG-SGZ, CA3 and CA1 area of the hippocampus. Seven days after KA treatment, substantial cell loss was found in the CA3 and CA4 areas, and the number of BrdU-labeled cells in the DG-SGZ markedly increased as compared with that in the saline group, especially on the same side of injection （P=0.006）. The number of noggin mRNA-positive cells in the hippocampus significantly increased 3 days after KA injection, and began to decrease on day 7. Conclusion The granular cell proliferation in the DG-SGZ after KA-induced rat hippocampal injury is probably associated with noggin expression changes in the hippocampus.