西洛他唑通过P38 MAPK信号途径对大鼠脑缺血再灌注损伤的保护作用  

Protection Effect of Cilostazol on Cerebral Ischemia /reperfusion in Rats via P38 MAPK Pathway

作　　者：蓝琳友[1] 洪溪屏[1] 蔡元晖[1] 

机构地区：[1]温州医科大学附属第五医院,丽水323000

出　　处：《医学研究杂志》2014年第5期107-110,共4页Journal of Medical Research

摘　　要：目的探讨西洛他唑对大鼠脑缺血再灌注损伤的保护作用及其作用机制。方法将75只成年雄性SD大鼠按数字表法随机分成假手术组、模型组、西洛他唑低剂量(10mg/kg)组、西洛他唑中剂量(20mg/kg)组和西洛他唑高剂量(40mg/kg)组,每组15只,通过大脑中动脉阻塞法建立起脑缺血再灌注模型。按照Longa EZ法评估动物神经功能;Tunel染色法检测大鼠脑神经细胞凋亡,采用Western blot法检测半胱氨酸蛋白酶3(caspase-3)及丝裂原活化蛋白激酶(MAPK)信号转导通路相关蛋白的表达。结果与假手术组相比较,模型组神经功能评分和细胞凋亡率均升高,差异有统计学意义;西洛他唑组的神经功能评分和细胞凋亡率较模型组均降低(P<0.05);与模型组相比较,caspase-3和MAPK信号转导通路中p-P38的表达水平均随西洛他唑剂量的增加而逐渐降低(P<0.05),而西洛他唑对MAPK信号转导通路中其他成员p-ERK和p-JNK的表达无明显影响。结论西洛他唑对大鼠脑缺血再灌注损伤的保护作用与抑制神经细胞凋亡有关,其抗凋亡作用机制可能与抑制P38 MAPK信号转导通路途径有关。Objective To elucidate the anti - apoptotic protection and the mechanism of cilostazol on focal cerebral ischemia/reperfusion （I/R） in rats. Methods Seventy - five healthy male SD rats were divided into five groups （n = 15） for experiments ： sham - op- erated group, ischemia/reperfusion （I/R） group, the low dose cilostazol （10mg/kg） group, the middle dose cilostazol （20mg/kg） group and the high dose cilostazol （40mg/kg） group. The neurofunction was measured by Longa EZ method. The Tunel test kit was used to ex- plore the cellular apoptosis in hippocampus. The expression of caspase - 3, MAPKs, p - P38, p - ERK and p - JNK were detected by western blot. Results As compared with the sham -operated group, the score of neurofunction and apoptotic cells in I/R group was in- creased statistically. The score of neurofunction and apoptosis rate in each cilostazol group was lower than that of I/R group. Compared with the I/R group, the expression of caspase - 3 and p - P38 was down - regulation in cilostazol group in a dose - dependent manner. Conclusion Cilostazol has certain neroprotective effect in rats after ischemia/reperfusion injury, which may be related to down - regula- tion of the level of P38 MAPK pathway.

关 键 词：脑缺血再灌注 凋亡 P38 

分 类 号：R393[医药卫生—基础医学]