JNK抑制剂SP600125通过下调MMP-9的表达减轻大鼠脑缺血再灌注损伤  

C-Jun N-terminal kinase inhibitor SP600125 attenuates cerebral ischemia-reperfusion injury in rats by downregulating MMP-9 expression

作　　者：徐晨晨 符浩[2] 朱红艳[3] 孟强[2] Xu Chenchen;Fu Hao;Zhu Hongyan;Meng Qiang(Medicine Faculty of Kunming University of Science and Technology,Kunming 650093,China;Department of Neurology,First People's Hospital of Yunnan Province,Kunming 650032,China;Department of Clinical Laboratory,First People's Hospital of Yunnan Province,Kunming 650032,China)

机构地区：[1]昆明理工大学医学院,昆明650093 [2]云南省第一人民医院神经内科,昆明650032 [3]云南省第一人民医院检验科,昆明650032

出　　处：《中华神经医学杂志》2020年第5期449-453,共5页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金(81460188)。

摘　　要：目的探讨大鼠脑缺血再灌注后c-Jun氨基末端激酶(JNK)及基质金属蛋白酶-9(MMP-9)表达的变化,以及JNK抑制剂SP600125能否通过下调MMP-9的表达对大鼠脑缺血再灌注损伤起脑保护作用。方法85只成年雄性SD大鼠按随机数字表法分为假手术组(n=35)、缺血组(n=35)及SP600125组(n=15)。后2组大鼠采用线栓法制备成右侧大脑中动脉闭塞模型,并缺血1 h后予再灌注,其中SP600125组在脑缺血前30 min侧脑室内注射SP600125溶液(溶于10%二甲基亚砜中,终浓度为20 mmol/L)。于再灌注后48 h时评估各组大鼠的神经功能缺损评分、缺血灶体积比、脑组织含水量;于再灌注后3 h、6 h、24 h及48 h时对假手术组、缺血组大鼠,再灌注后48 h时对SP600125组大鼠采用Western blotting检测缺血皮层中磷酸化(p)-JNK、JNK及MMP-9蛋白的表达水平。结果与假手术组相比,再灌注后48 h时,缺血组大鼠的神经功能缺损评分明显降低,缺血灶体积比、脑组织含水量明显升高,差异均有统计学意义(P<0.05);再灌注后24 h、48 h时,缺血组大鼠缺血皮层中p-JNK/JNK值、MMP-9蛋白水平均明显升高,差异均有统计学意义(P<0.05)。与缺血组相比,再灌注后48 h时,SP600125组大鼠的神经功能缺损评分明显升高,缺血灶体积比、脑组织含水量明显降低,缺血皮层中p-JNK/JNK值、MMP-9蛋白水平均明显降低,差异均有统计学意义(P<0.05)。结论脑缺血再灌注后JNK及MMP-9的表达均明显升高,而JNK抑制剂SP600125可通过下调MMP-9的表达以减轻脑缺血再灌注损伤程度,从而起到脑保护作用。Objective To investigate the changes of c-Jun N-terminal kinase(JNK)and matrix metalloproteinase-9(MMP-9)expressions after cerebral ischemia-reperfusion in rats and whether JNK inhibitor SP600125 can protect the cerebral ischemia-reperfusion injury by down-regulating the expression of MMP-9.Methods Eighty-five adult male SD rats were divided into sham-operated group(n=35),ischemia group(n=35)and SP600125 group(n=15).The middle cerebral artery occlusion models in rats of ischemia group and SP600125 group were established by thread embolism method,and reperfusion was performed one h after ischemia.Rats in the SP600125 group were injected with SP600125 solvent(being dissolved in 10%dimethyl sulfoxide with final concentration of 20 mmol/L)in the lateral ventricle 30 min before cerebral ischemia.At 48 h after reperfusion,neurological impairment scale scores,volume ratio of ischemic lesion,and moisture content of brain tissues in rats from each group were evaluated.The protein expression levels of phosphorylated(p)-JNK,JNK and MMP-9 in the ischemic cortex were detected by Western blotting in rats from the sham-operated group and ischemic group at 3,6,24 and 48 h after reperfusion,and in rats from SP600125 group at 48 h after reperfusion.Results As compared with the sham-operated group,rats in the ischemia group had significantly decreased neurological impairment scale scores,and significantly increased infarction volume ratio and moisture content of brain tissues 48 h after reperfusion.At 24 and 48 h after reperfusion,the p-JNK/JNK values and MMP-9 protein level in the ischemia group were significantly increased as compared with those in the sham-operated group(P<0.05).As compared with the ischemia group,at 48 h after reperfusion,rats in the SP600125 group had significantly increased neurological impairment scale scores,and significantly reduced volume ratio of ischemic lesion and moisture content of brain tissues,and significantly reduced p-JNK/JNK values and MMP-9 protein level in the ischemic cortex(P<0.05).Conclusi

关 键 词：脑缺血再灌注损伤 C-JUN氨基末端激酶 基质金属蛋白酶-9 血脑屏障 

分 类 号：R74[医药卫生—神经病学与精神病学]