ERK1/2和Akt通路对控制性低压后处理兔缺血/再灌注损伤脊髓线粒体功能的影响  

Effect of Akt and ERK1/2 pathway in the mitochondrial function by controlled low perfusion pressure against spinal ischemia/reperfusion in rabbits

作　　者：艾春雨[1] 江晓菁[1] 马虹[1] 王俊科[1] 

机构地区：[1]中国医科大学附属第一医院麻醉科,辽宁沈阳110005

出　　处：《中国药理学通报》2012年第8期1084-1087,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30740092)

摘　　要：目的研究PI3K/Akt和ERK1/2通路对控制性低压后处理兔缺血/再灌注损伤脊髓线粒体功能的影响。方法30只日本大耳白兔随机分为5组(n=6):假手术组(Sham)、缺血/再灌注组(I/R),控制性低压后处理组(Post),控制性低压后处理+PD98059组(Post+PD)、控制性低压后处理+LY294002组(Post+LY)组。除Sham组外,其余各组分别于肾动脉下水平阻断腹主动脉25 min。Post组:再灌注开始10 min采用控制性低灌注压后处理法球囊部分排空,将腹主动脉远端血压控制在5.99～7.32 kPa,10min后球囊完全开放。Post+PD组、Post+LY组:同Post组,并分别于腹主动脉开放前1 min鞘内注射ERK抑制剂PD98059(3μg,20μl)、PI3K/AKT抑制剂LY294002(10μg,20μl)。再灌注24 h后将实验动物处死,取脊髓组织用Western blot技术测定Caspase-3、胞质Cytochrome C蛋白表达;电镜观察线粒体结构。结果与I/R组比较,Post组Caspase-3和胞质Cytochrome C蛋白表达明显减少,线粒体结构破坏减轻。ERK抑制剂PD98059和PI3K/Akt抑制剂LY294002减弱了Post的作用。结论控制性低压后处理对缺血/再灌注损伤脊髓线粒体功能有保护作用,其机制可能与激活PI3K/Akt和ERK1/2通路有关。Aim To observe the influence of Akt and ERK1/2 pathway on the mitochondrial function by controlled low perfusion pressure against spinal ischemiareperfusion. Methods Thirty Japanese white rabbits weighing 2. 0 - 2.5 kg were randomly divided into five groups（ n = 6 ） ： sham group, ischemia/reperfusion （ I/ R） group, controlled low perfusion pressure ischemic postconditioning（Post） group, Post ＋ PD98059 （Post ＋PD） group and Post ＋ LY294002 （Post ＋ LY） group. Except sham group, the spinal isehemia was in- duced by occlusion of the infrarenal aorta for 25 rain. Post group： postconditioning was accomplished by the blood flow partially restored and the mean blood pressure of the distal aorta was controlled between 5.99 and 7.32 kPa by adjusting the volume of the balloon during the first 10 min of reperfusion. Post ＋ PD and Post ＋ LY group ： PD98059 （ 3 μg, 20 μl, a specific ERK1/2 inhibitor） and LY294002 （ 10 μg, 20μl, a specific PI3K/Akt inhibitor） were intravenously administered 1 minute before ischemic postconditioning. All rabbits were sacrificed 1 d after reperfusion , the spinal cord was removed for determination of the expression of Caspase-3 and Cytochrome C by Western blot and the ultrastruetural change of mitoehondrial was observed by electronmieroscope. Results Compared with I/R group, the expressions of Caspase-3 and Cy- tochrome C were decreased, and ultrastrncture of mitochondrial was less damaged in Post group. However, the protective effect of Post was reduced by PD98059 and LY294002. Conclusion Controlled low perfusion pressure can reduce the spinal cord I/R injury through activiting PI3K/Akt and ERK1/2 pathways and protecting mitochondrial function.

关 键 词：控制性低压 缺血/再灌注损伤 缺血后处理 脊髓 AKT ERK 线粒体 

分 类 号：R332[医药卫生—人体生理学] R322.81[医药卫生—基础医学]