新生大鼠缺氧缺血脑损伤时脑组织STAT3信号通路的作用.docVIP

PAGE [基金项目] 国家自然科学基金资助项目（No.，四川省青年科技基金项目（No. 08ZQ026-069） [作者简介] 邓睿，女，四川大学华西第二医院新生儿专业硕士，现任职于重庆市妇幼保健院。 [通信作者] 母得志，Email：mudz@ 新生大鼠缺氧缺血脑损伤时脑组织STAT3信号通路的作用 邓睿1 周立刚1赵凤艳2 张莉2李德渊2 母得志2 （400013 重庆，重庆市妇幼保健院新生儿科；610041 四川 成都，四川大学华西第二医院儿科2） [摘 要] 目的 研究信号转导和转录激活因子3（STAT3）信号通路在新生大鼠缺氧缺血（ HI ）脑损伤中的作用。方法 采用 Rice 法建立 7 日龄 SD 大鼠缺氧缺血脑损伤（HIBD）模型，同时设立对照。于 HI 后 4 h、6 h、8 h、12 h 和 24 h 取脑，采用免疫组织化学法及 Western blot 检测 STAT3、 磷酸化 STAT3（p-STAT3）及血管内皮生长因子（VEGF）的表达与分布，TUNEL 法检测神经细胞凋亡。结果 HI 组 p-STAT3 蛋白表达在 HI 后 4 h 升高，6 h 达高峰，8 ~ 12 h 逐渐下降，均明显高于假手术组，差异有统计学意义（P﹤0.05）。而 STAT3 总蛋白表达与假手术组比较，差异无统计学意义（P﹥0.05）。VEGF 于 HI 后各时间点均明显高于假手术组，差异有统计学意义（P﹤0.05）。TUNEL 染色阳性细胞数于 HI 后 24 h 达高峰，明显高于假手术组，差异有统计学意义( P﹤0.01 )。结论 新生大鼠 HI 后，p-STAT3 蛋白表达增高，可能诱导 VEGF 表达，对神经元的凋亡具有抑制作用。 [关 键 词] 信号转导和转录激活因子；STAT3；血管内皮生长因子；凋亡；缺氧缺血性脑损伤；新生大鼠 [中图分类号] R-72 [文献标识码] A [文章编号] The function of STAT3 signaling pathway in neonatal rats following hypoxic-ischemia brain damage Abstract ：Objective To investigate the function of STAT3 signaling pathway in neonatal rats under hypoxia ischemia (HI) condition. Methods Hypoxic-ischemia brain injury animal model was made using 7-day-old SD rats according to Rice-Vannucci model, and comparative studies were made with a sham group. Brain tissues were collected after 4 h、6 h、8 h、12 h and 24 h of recovery from HI. Immunohistochemistry and western blot were used to detect the expression and distribution of STAT3, phosphorylated STAT3 (p-STAT3) and vascular endothelial growth factor (VEGF); cell apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining. Results In the HI group, The p-STAT3 protein significantly increased at 4 hours, reached the peak at 6 hours, began to decrease at 8-12 hours, which were significant higher than those in the sham group (P﹤0.05). There was no significant difference observed when compared the expression of total STAT3 protein in the HI group with those of the sham group. In the HI group, the VEGF expression was higher