摘要
目的评价细胞外信号调节激酶(ERK)传导通路对低压灌注缺血后处理兔缺血/再灌注损伤脊髓的保护作用及机制。方法 84只日本大耳白兔随机分为7组,分别为C组(对照组,不给予缺血后处理)、PB组(缺血后处理组)、D、PD1、PD3、PD9组分别于腹主动脉开放前1min鞘内注射DMSO 20μl、PD98059 1μg(20μl)、PD98059 3μg(20μl)、PD98059 9μg(20μl)之后进行缺血后处理及PD组(腹主动脉开放前1min鞘内注射PD98059 3μg(20μl),之后不行缺血后处理)。分别于再灌注1、3、7、28d时采用Tarlov评分评价后肢运动功能。每组于再灌注1d时处死6只动物,取L3~5节段脊髓组织,采用West-ern blot技术测定p-ERK1/2及Bcl-2,Bax蛋白表达。结果 1、3、7、28d,PB组Tarlov评分明显高于其它各组(P<0.05),缺血后处理可以明显上调p-ERK1/2及凋亡抑制基因Bcl-2的表达,下调凋亡促进基因Bax的表达(P<0.05),而这些调节作用可以被ERK1/2阻断剂PD98059抑制。结论 p-ERK1/2在低压灌注缺血后处理对缺血再灌注损伤脊髓的保护中起重要作用。
Objective To study the neuroprotective effect of the ischemic postconditioning by con- trolled low perfusion pressure, and investigate the activity of the signal pathway of extracellular signal-related kinases (ERK). Methods Eighty-four white Japanese rabbits weighing between 2.0-2.5kg were randomly divided into 7 groups, the control group (group C) ; the ischemic postconditioning group (group PB), group D, PD1, PD3, PD9 which were given intrathecal injections of DMSO 20μl PD98059 μg (20μl), PD98059 3μg(20μl), PD98059 9μg(20μl)1 minute before ischemic postconditioning; group PD which was given intrathecal injection of PD98059 3μg(20μl) but without ischemic postconditioning. Tarlov scores were assessed during a 28-day observation period. Six rabbits from each group were sacrificed 1 d after reperfusion and L3-5 segments of the spinal cord were removed for determination of the expression of p-ERK1/2, Bcl-2 and Bax by Western blot. Results The Tarlov scores were markedly increased during 28 days with ischemic postconditioning, which enhanced the expressions of phospho-ERK and Bcl-2 and decreased the Bax expression in the spinal cords(P〈0.05). The neuroprotective effects and the increased phospho-ERK were abolished by the administration of ERK inhibitor PD98059. Conclusion The ischemic postconditioning with low-pressure perfusion exerts comparable neuroprotective effects on the spinal cord, and ERK pathways play crucial roles in the molecular mechanism.
出处
《中国组织化学与细胞化学杂志》
CAS
CSCD
2012年第1期5-8,共4页
Chinese Journal of Histochemistry and Cytochemistry
基金
国家自然科学基金资助(30740092)
关键词
缺血后处理
缺血再灌注损伤
ERK
脊髓
Postconditioning
Ischemia/reperfusion injury
ERK
Spinal cord