rt-PA联合高压氧对大鼠脑缺血再灌注损伤的保护作用及其机制  

The effect and mechanism of rt-PA combined with high pressure oxygen on cerebral ischemia-reperfusion injury in rats

作　　者：毕庆国 刘春兰[2] 付建辉[1] 李清华[1] 储新娟[1] 肖伟忠[1] 

机构地区：[1]复旦大学附属浦东医院,上海市浦东医院神经内科,上海201399 [2]复旦大学附属浦东医院,上海市浦东医院心内科,上海201399

出　　处：《西安交通大学学报（医学版）》2016年第3期372-377,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：浦东新区卫生局卫生科技面上项目(No.PW2013A-18)~~

摘　　要：目的观察比较rt-PA联合高压氧(high pressure oxygen,HPO)对大鼠局灶性脑缺血/再灌注损伤后的神经保护作用,并探讨其作用机制。方法采用大脑中动脉线栓法制备大鼠局灶性缺血再灌注模型,观察比较rt-PA联合HPO对大鼠缺血再灌注损伤后神经功能、脑含水量、脑指数、脑梗死体积、超氧化物歧化酶(SOD)、丙二醛(MDA)、乳酸(LD)、乳酸脱氢酶(LDH)、一氧化氮合酶(NOS)及一氧化氮(NO)的影响。采用Western blot和RT-PCR观察比较rt-PA联合HPO对大鼠缺血再灌注损伤后诱导型NOS(iNOS)、脑源性神经营养因子(BDNF)、神经营养受体p75(p75NTR)和TrkB蛋白及mRNA的表达。结果 rt-PA联合HPO组比rt-PA组更显著地降低模型大鼠的神经功能评分、脑含水量、脑指数、脑梗死体积、SOD、MDA、LD、NOS、NO及iNOS和p75NTR蛋白及mRNA的表达;升高模型大鼠的体质量、LDH及BDNF和TrkB蛋白及mRNA的表达(P<0.05)。结论 rt-PA联合HPO对大鼠脑缺血再灌注损伤具有更显著的保护作用,其机制可能与抗氧化、减少iNOS的表达,上调BDNF及其高亲和力受体TrkB的表达、下调低亲和力受体p75NTR的表达等有关。Objective To evaluate the effect and mechanism of rt-PA combined with high pressure oxygen （HPO） on cerebral ischemia-reperfusion injury in rats. Methods The model of cerebral isehemia-reperfusion injury was constructed by using middle cerebral artery occlusion. The neurological function score; brain index, water content and infarction volume; SOD; LDH; NOS; MDA; LD; NO and NOS were measured. The protein and mRNA expressions of iNOS, BDNF, p75NTR and TrkB were also detected by RT-PCR and Western blot to evaluate and compare the protective effect of rt-PA combined HPO therapy. Results rt-PA combined HPO could significantly decrease the neurological function score; brain index, water content, and infarction volume; SOD; NOS; MDA; LD; NO and NOS but increase LDH content and the weight of rats, compared with rt-PA. In addition, rt-PA combined HPO could increase BNDF and TrKB expressions and downregulate the expressions of iNOS and p75NTR, compared with rt-PA （P^0. 05）. ConcIusion The rt-PA combined HPO therapy has a greater protective effect than rt-PA therapy and its mechanism might be related to having antioxidant effects, increasing the expressions of BDNF and TrKB, and decreasing the expressions of iNOS and p75NTR.

关 键 词：RT-PA 高压氧 联合治疗 脑缺血再灌注 神经保护 

分 类 号：R743.33[医药卫生—神经病学与精神病学]