马来酸桂哌齐特预处理对脑缺血大鼠MAPK信号转导通路的影响

Effects of preconditioning with cinepazide maleate on MAPK signal transduction pathway of rats with cerebral ischemia

目的观察马来酸桂哌齐特预处理对脑缺血大鼠胞外信号调节激酶(ERK)1/2和p38丝裂原激活蛋白激酶(p38 MAPK)表达的影响,并探讨该药物的脑保护作用。方法将SD大鼠随机分为马来酸桂哌齐特预处理脑缺血手术组(给药手术组)、生理盐水预处理脑缺血手术组(对照手术组)和马来酸桂哌齐特预处理非手术组(给药非手术组),每组30只,预处理时间均为5 d。对两手术组大鼠行改良线栓法手术建立左侧大脑中动脉阻塞脑缺血模型,分别于术后8、24、72 h断头取脑,切取左侧(缺血侧)及右侧相应脑组织,Western blotting检测各时间点双侧脑组织中ERK1/2和p38 MAPK表达及其磷酸化水平(p-ERK1/2和p-p38 MAPK表达)。结果各组大鼠脑组织中ERK1/2和p38 MAPK总蛋白的相对表达量比较差异均无统计学意义(P>0.05)。与给药非手术组比较,给药手术组和对照手术组术后8 h左侧(手术侧)脑区的p-ERK1/2蛋白相对表达量均显著上调,术后24 h和72 h的p-ERK1/2蛋白相对表达量均显著下调,差异均有统计学意义(P<0.05)。与给药非手术组比较,给药手术组和对照手术组术后8、24、72 h左侧脑区的p-p38 MAPK蛋白相对表达量均显著上调,且对照手术组高于给药手术组,差异有统计学意义(P<0.05)。结论马来酸桂哌齐特可能在脑缺血早期发挥脑保护作用。

Objective To observe the effects of preconditioning with cinepazide maleate on the expressions of extraceUular signal regulated kinases （ERK1/2） and p38 mitogen-activated protein kinase （p38 MAPK） of rats with cerebral ischemia and to explore the neuroprotective function of cinepazide maleate. Methods SD rats were randomly divided into the cinepazide maleate injection preconditioning operation group （treatment-operation group）, normal saline injection preconditioning operation group （control-operation group）, and cinepazide maleate injection preconditioning non-operation group （ treatment-non-operation group）. Each group had 30 rats and was preconditioned for 5 days. The cerebral ischemia models were established by occluding the left middle cerebral artery of rats in two operation groups through a modified suture method. At 8 h, 24 h, and 72 h after operations, brain tissues were taken out and their left side （ischemic side） and the corresponding right side were excised. The expressions and phosphorylation levels （the expressions of p-ERK1/2 and p-p38 MAPK） of ERK1/2 and 1038 MAPK in both sides of brain tissues at each time point were detected by the Western blotting. Results The differences of relative expressions of total proteins of ERK1/2 and p38 MAPK in rat brain tissues from each group were not statistically significant （P〉0.05）. Gompared to the treatment-non-operation group, the relative expressions of p-ERK1/2 protein in left side （operation side） of brain tissues of rats in the treatment- operation group and control-operation group at 8 h after operations were significandy up-regulated and weresignificantly down-regulated at 24 h and 72 h after operations. The differences were statistically significant （P 〈 0.05）. Also compared to the treatment-non-operation group, the relative expressions of p-p38 MAPK protein in left side （ operation side） of brain tissues of rats in the treatment-operation group and control-operation group at 8 h, 24 h, and 72 h after operations were siguificantly up-regulated and the expressions of p-p38 MAPK protein of control-operation group was statistically higher than that of the treatment-operation group. The differences were statistically significant （ P 〈 0.05）. Conclusion Cinepazide maleate may have protective effects at the early stage of cerebral ischemia.