MCC950对大鼠脑缺血再灌注损伤后NLRP3炎性小体活化的影响  

Effects of MCC950 on activation of NLRP3 inflammasome after cerebral ischemiareperfusion injury in rats

作　　者：潘海英[1] 张楠 周悦 李晓云[1] PAN Hai-ying;ZHANG Nan;ZHOU Yue;LI Xiao-yun(Department of Neurorehabilitation,Yidu Central Hospital of Weifang,Weifang SHANDONG 262500,China)

机构地区：[1]潍坊市益都中心医院神经康复科,山东潍坊262500

出　　处：《中国新药与临床杂志》2022年第12期754-758,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：山东省潍坊市科技发展计划项目(2019YX096)。

摘　　要：目的探讨MCC950对脑缺血再灌注损伤大鼠神经功能的保护作用及可能的机制。方法48只雄性SD大鼠随机分为假手术组、模型组、溶剂组和MCC950组,每组12只。制备大鼠脑缺血再灌注损伤模型后,MCC950组腹腔注射MCC9503 mg·kg^(-1),qd×7 d,溶剂组则以同样的方式给予等量的生理盐水,假手术组和模型组不作任何药物干预。于再灌注24 h和末次给药后,利用Zea-Longa法对各组大鼠进行神经功能缺损评分,TTC染色法测定脑梗死体积,实时荧光定量PCR术检测脑梗死区组织中NLRP3、ASC和caspase-1基因表达,Western blot法检测脑梗死区组织中NLRP3、ASC、pro-caspase-1和caspase-1蛋白表达,酶联免疫吸附试验检测脑梗死区组织中白细胞介素(IL)-1β和IL-18水平。结果与假手术组比较,模型组、溶剂组和MCC950组大鼠再灌注24 h后和末次给药后神经功能缺损评分升高,脑梗死体积百分比升高,脑梗死区组织中NLRP3、ASC和caspase-1 mRNA和蛋白表达量升高,pro-caspase-1蛋白表达量降低,IL-1β和IL-18水平升高,差异均有显著意义(P<0.05)。与模型组和溶剂组比较,MCC950组大鼠末次给药后神经功能缺损评分降低,脑梗死体积百分比降低,脑梗死区组织中NLRP3、ASC和caspase-1 mRNA和蛋白表达量降低,pro-caspase-1蛋白表达量升高,IL-1β和IL-18水平降低,差异均有显著意义(P<0.05)。结论MCC950可有效改善脑缺血再灌注损伤大鼠神经功能,减少脑梗死体积,其作用机制可能与抑制NLRP3炎性小体活化介导的炎症反应有关。AIM To study the protective effects of MCC950 on neurological function of rats with cerebral ischemiareperfusion injury and the possible mechanisms.METHODS A total of 48 male SD rats were randomly divided into sham operation group,model group,solvent group and MCC950 group(12 rats per group).After successfully establishing the rat model of cerebral ischemia-reperfusion injury,the MCC950 group were intraperitoneally injected with MCC950at the dose of 3 mg·kg^(-1),qd×7 d,the solvent group were given the same amount of normal saline in the same way,and no drug intervention was made in the sham operation group and the model group.After 24 hours of reperfusion and the last administration,the neurological deficit score of rats in each group was evaluated by Zea-Longa method.The cerebral infarction volume was measured by TTC staining.Real-time quantitative PCR was used to detect the expressions of NLRP3,ASC and caspase-1 genes in cerebral infarction area.Western blot analysis was used to detect the expressions of NLRP3,ASC,pro-caspase-1 and caspase-1 proteins in cerebral infarction area.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin(IL)-1β and IL-18 in cerebral infarction area.RESULTS Compared with the sham operation group,the neurological deficit scores at 24 hours after reperfusion and after the last administration in the model group,solvent group and MCC950 group were increased,the percentages of cerebral infarction volume were increased,the expression levels of NLRP3,ASC and caspase-1 mRNA and proteins were increased,the expression level of pro-caspase-1protein was decreased,and the levels of IL-1β and IL-18 were increased(P<0.05).Compared with the model group and the solvent group,the neurological deficit score after the last administration in the MCC950 group was decreased,the percentage of cerebral infarction volume was decreased,the expression levels of NLRP3,ASC and caspase-1 mRNA and proteins were decreased,the expression level of pro-caspase-1 protein was increased,an

关 键 词：脑缺血 再灌注损伤 MCC950 NLRP3蛋白 大鼠 

分 类 号：R961[医药卫生—药理学]