橄榄苦苷对脑缺血再灌注损伤大鼠神经元凋亡及JNK/p38 MAPK信号通路的影响

Effects of oleuropein on apoptosis of neurons and JNK/p38 MAPK signaling pathway in rats with cerebral ischemia-reperfusion injury

目的研究橄榄苦苷对脑缺血再灌注损伤大鼠神经元凋亡及c-Jun氨基末端激酶(JNK)/促分裂素原活化蛋白激酶(p38 MAPK)信号通路的影响。方法SD大鼠随机分为假手术组、模型组、尼莫地平组(0.5 mg/kg)及橄榄苦苷高、低剂量组(40、20 mg/kg),每组14只。连续灌胃给药14 d,末次给药结束后采用线栓法建立脑缺血再灌注损伤模型,进行2 h缺血后再灌注24 h,测定神经症状评分、脑梗死面积、脑组织含水量、半胱氨酸蛋白酶(Caspase)-3、B淋巴细胞瘤(Bcl)-2、Bcl-2相关的x蛋白(Bax)mRNA表达及磷酸化的JNK(p-JNK)、磷酸化的p38 MAPK(p-p38)蛋白表达等指标。结果与模型组比较,橄榄苦苷高、低剂量组大鼠神经症状评分、脑梗死面积及橄榄苦苷高剂量组脑组织含水量均显著降低(P<0.05);与模型组比较,橄榄苦苷高、低剂量组大鼠Caspase-3、Bax mRNA及p-JNK、p-p38蛋白表达均明显降低(P<0.05),而Bcl-2 mRNA表达明显增加(P<0.05)。结论橄榄苦苷对大鼠脑缺血再灌注损伤具有保护作用,该作用与抑制JNK/p38 MAPK信号通路的活化进而减少神经元凋亡有关。

Objective To study the effects of oleuropein on apoptosis of neurons and JNK/p38 MAPK signaling pathway in rats with cerebral ischemia-reperfusion injury(CIRI).Methods SD rats were divided into sham,model,positive drug nimodipine(0.5 mg/kg)and high and low dose oleuropein groups(40 and 20 mg/kg),with 14 rats in each group.After 14 days of continuous intragastric administration,the CIRI model was established by the line bolt-method after the last administration,the neurological symptom score,cerebral infarction area,cerebral water content,Caspase-3,Bcl-2,Bax mRNA,p-JNK and p-p38 protein expressions were measured after 2 h of ischemia and 24 h reperfusion.Results Compared with model group,the neurological symptom score,cerebral infarction area in the high and low dose oleuropein groups,and cerebral water content in the high dose oleuropein group were significantly decreased(P<0.05);compared with model group,Caspase-3,Bax mRNA,p-JNK and p-p38 protein expressions were decreased,while the expression of Bcl-2 mRNA were significantly increased in the oleuropein groups(all P<0.05).Conclusions Oleuropein has a protective effect on CIRI rats,which is related to inhibit the activation of JNK/p38 MAPK signaling pathway and thereby reduce the apoptosis of neurons.