经典Wnt信号通路在大鼠脑缺血后血管新生中的作用

doi:10.6040/j.issn.1671-7554.0.2014.775

摘要/Abstract

摘要： 目的研究缺血性脑卒中大鼠缺血周边脑组织的经典Wnt信号通路活性及干预该通路活性对缺血周边血管新生的影响.方法随机将50只雄性Wistar大鼠分为4组:假手术组(Sham组, n=10),脑缺血对照组(MCAO组, n=20),氯化锂干预组(LiCl组, n=10),DKK1干预组(DKK1组, n=10).免疫印迹法检测经典Wnt信号通路成分,FITC-dextran检测血管密度,多普勒血流仪检测血流量.结果脑缺血1 d后,与Sham组相比,MCAO组缺血周边脑组织细胞核蛋白及细胞浆蛋白中β-catenin表达水平显著下降(P< 0.05),7 d时明显恢复,14 d时接近正常水平.与MCAO组相比,LiCl组β-catenin表达水平及p-GSK-3β/GSK-3β比值提高(P< 0.05),并且缺血周边血管密度及血流量增加(P< 0.05);DKK1组变化相反,β-catenin表达水平及p-GSK-3β/GSK-3β比值降低(P< 0.05),血管密度及血流量下降(P< 0.05).结论经典Wnt信号通路参与调节缺血性脑卒中后缺血周边的血管新生.

关键词: 缺血性脑卒中, 人工气道, 误吸, -catenin, 血管新生, &beta, 大鼠, 经典Wnt信号通路, 气囊压力, 黏膜损伤

Abstract: Objective To investigate the involvement of canonical Wnt pathway in postischemic angiogenesis by using a rat model of ischemic stroke. Methods A total of 50 normal male Wistar rats were randomly divided into 4 groups: Sham group (n=10), cerebral ischemia group (MCAO group, n=20), LiCl treated group (LiCl group, n=10) and DKK1 treated group (DKK1 group, n=10). Western blotting was used to detect the expression of the elements of canonical Wnt pathway. FITC-dextran was used to detect the vessel volume, and Laser Doppler was used to measure the local cerebral blood flow in ischemic penumbral. Results The expressions of β-catenin in both the nuclear fraction and the cytoplasmic fraction in MCAO group decreased at 1 day post-cerebral ischemia, compared with Sham group(P< 0.05). Nevertheless, the expressions of β-catenin in both the nuclear fraction and the cytoplasmic fraction at 7 day post-cerebral ischemia significantly increased (P< 0.05), and reached normal level at 14 day post-cerebral ischemia. Compared with MCAO group, the expressions of β-catenin in both the nuclear fraction and the cytoplasmic fraction LiCl group in were upregulated, accompanied with the elevated ratio of p-GSK-3β/GSK-3β, enhanced vessel volume and local cerebral blood flow in ischemic penumbral(P< 0.05). Compared with MCAO group, the expressions of β-catenin in DKK1 group in both the nuclear fraction and the cytoplasmic fraction were downregulated, accompanied with the decreased ratio of p-GSK-3β/GSK-3β, weakened vessel volume and local cerebral blood flow in ischemic penumbral(P< 0.05). Conclusion The canonical Wnt pathway might be involved in postischemic angiogenesis.

Key words: Canonical Wnt pathway, Rats, β-catenin, Angiogenesis, Ischemic stroke

中图分类号:

R614.2

陈海丽, 顾娇阳, 张文静, 袁琳冉, 郑娟, 袁中瑞. 经典Wnt信号通路在大鼠脑缺血后血管新生中的作用[J]. 山东大学学报（医学版）, 2015, 53(4): 31-36.

CHEN Haili, GU Jiaoyang, ZHANG Wenjing, YUAN Linran, ZHENG Juan, YUAN Zhongrui. Involvement of canonical Wnt pathway in postischemic angiogenesis in a rat model of ischemic stroke[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(4): 31-36.

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