4-辛基衣康酸对大鼠短暂性脑缺血再灌注模型的保护作用及机制探究  

Protective Effect and Mechanism of 4-octyl Itaconate on Rat Models with Transient Cerebral Ischemia-Reperfusion

作　　者：樊丽超[1] 左秀美[2] 周立春[1] FAN Li-chao;ZUO Xiu-mei;ZHOU Li-chun(Department of Neurology,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100043,China;Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学附属北京朝阳医院神经内科,北京100043 [2]首都医科大学宣武医院神经内科,北京100053

出　　处：《解放军医药杂志》2021年第6期1-6,共6页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金青年基金项目(81100799)。

摘　　要：目的探究4-辛基衣康酸(4-OI)对短暂性脑缺血再灌注模型大鼠的保护作用及机制。方法选取36只清洁级SD级大鼠,采用随机数字表法分为对照组、模型组和治疗组,每组12只。对照组和模型组大鼠腹腔注射生理盐水,治疗组大鼠腹腔注射4-OI 100 mg/kg。采用“线栓法”制作大鼠中动脉栓塞模型;对照组行假手术,缺血1 h后恢复血流。手术24 h后对3组大鼠神经功能损伤程度及脑组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和白细胞介素-1β(IL-1β)含量进行评估。比较3组大鼠梗死区脑组织核因子E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)、硫氧还蛋白互作蛋白(TXNIP)和核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)表达水平。结果与对照组比较,模型组大鼠神经功能评分和脑梗死面积百分比增高(P<0.01)。与模型组比较,治疗组大鼠神经功能评分减低,脑梗死面积百分比减少,差异有统计学意义(P<0.01)。与对照组比较,模型组MDA含量显著升高,SOD含量显著降低,差异有统计学意义(P<0.01)。与模型组比较,治疗组MDA含量减低,SOD含量增高,差异有统计学意义(P<0.01)。与对照组比较,模型组IL-1β含量、TXNIP、NLRP3、Nrf2和HO-1蛋白表达量均升高,差异有统计学意义(P<0.01)。与模型组比较,治疗组IL-1β含量、TXNIP和NLRP3蛋白表达量均降低,Nrf2和HO-1蛋白表达量均增高,差异有统计学意义(P<0.01)。结论4-OI激活Nrf2/HO-1抗氧化应激通路,抑制TXNIP/NLRP3炎症通路,从而在脑缺血再灌注损伤方面起保护作用。Objective To explore the protective effect of 4-octyl itaconate(4-OI)on rat models with transient cerebral ischemia-reperfusion and its mechanism.Methods Thirty-six SD clearing rats were selected and divided into control group(n=12),model group(n=12)and treatment group(n=12)according to random number table method.Control and model groups were injected physiological saline intraperitoneally,while 4-OI 100 mg/kg was injected in treatment group.Rat models of middle cerebral artery occlusion were established by using suture occlusion method.Control group had received sham operation,and blood flow was restored after 1 hour of ischemia.After operation for 24 h,degrees of neurological function injury,and contents of malondialdehyde(MDA),superoxide dismutase(SOD)and interleukin-1β(IL-1β)in brain tissues were evaluated among the three groups.Levels of nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),thioredoxin interaction protein(TXNIP)and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)in brain tissues of the infarcted areas were compared among three groups.Results Compared with those in control group,values of neurological function score and percentage of cerebral infarct area were significantly increased in model group(P<0.0l).Compared with those in model group,values of neurological function score and percentage of cerebral infarct area were significantly decreased in treatment group(P<0.0l).Compared with those in control group,MDA content was significantly increased,while SOD content was significantly increased in model group(P<0.01).Compared with those in model group,MDA content was significantly decreased,while SOD content was significantly increased in treatment group(P<0.01).Protein expressions of IL-1β,TXNIP,NLRP3,Nrf2 and HO-1 in model group were significantly increased compared with those in control group,and the differences were statistically significant(P<0.01).Compared with those in model group,protein expressions of IL-1β,TXNIP and NLRP3 we

关 键 词：脑缺血再灌注损伤 4-辛基衣康酸 Nrf2/HO-1通路 TXNIP/NLRP3通路 丙二醛 超氧化物歧化酶 大鼠 Sprague-Dawely 

分 类 号：R-332[医药卫生] R743.31