英夫利西单抗通过c-Jun N末端激酶通路减轻脑出血小鼠的炎症损伤  

Infliximab attenuates inflammatory injury in mice with intracerebral hemorrhage through c-Jun N-terminal kinase pathway

作　　者：严美茹 张燕平[2] 罗瑞琦 王思媛 刘向哲[3] 蒋超[4] YAN Mei-ru;ZHANG Yan-ping;LUO Rui-qi;WANG Si-yuan;LIU Xiang-zhe;JIANG Chao(First College of Clinical Medicine,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,Henan Province,China;Severe Neurological Condition,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China;Encephalopathy District,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China;Department of Neurology,the Fifth Affiliated Hospital of the Zhengzhou University,Zhengzhou 450052,Henan Province,China)

机构地区：[1]河南中医药大学第一临床医学院,河南郑州450046 [2]河南中医药大学第一附属医院神经重症,河南郑州450000 [3]河南中医药大学第一附属医院脑病一区,河南郑州450000 [4]郑州大学第五附属医院神经内科,河南郑州450052

出　　处：《中国临床药理学杂志》2023年第8期1099-1103,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河南省高等学校重点科研基金资助项目(22A320037);河南省中医药管理局基金资助项目(2022ZY1009)。

摘　　要：目的探讨英夫利昔单抗对小鼠脑出血炎症反应及c-Jun N-末端激酶(JNK)通路的影响。方法将C57BL/6小鼠随机分为假手术组、模型组、实验组,每组各12只。模型组、实验组通过胶原酶法建立脑出血模型,假手术组注入等体积的0.9%NaCl。造模后,实验组给予英夫利昔单抗(10 mg·kg^(-1)·d^(-1))尾静脉注射,连续3 d,假手术组、模型组每日给予等量0.9%NaCl尾静脉注射。用转角实验和mNSS评分法检测小鼠神经功能;用干湿重法对脑组织含水量进行测定;用蛋白质印迹法检测小鼠脑组织的白细胞介素-1β(IL-1β)、磷酸化c-Jun N-末端激酶(P-JNK)蛋白表达水平。结果干预3 d后,假手术组、模型组和实验组的左转率分别为(31.67±2.36)%、(13.33±2.36)%和(21.66±2.35)%,mNSS评分分别为(0.33±0.52)、(12.67±1.63)和(8.17±0.98)分,脑含水量分别为(78.08±0.86)%、(81.08±0.58)%和(79.67±1.13)%,IL-1β蛋白表达水平分别为0.64±0.06、0.90±0.03和0.80±0.06,P-JNK蛋白表达水平分别为0.31±0.09、0.57±0.02和0.46±0.04。实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论英夫利昔单抗能够通过抑制JNK信号通路,减轻炎症反应,发挥改善脑出血小鼠早期神经功能的作用。Objective To investigate the effect of infliximab on inflammatory response and c-Jun N-terminal kinase(JNK)pathway in mice with intracerebral hemorrhage(ICH).Methods C57BL/6 mice were randomly divided into sham operation group,model group and experimental group with 12 mice in each group.The model group and the experimental group were established by collagenase method,and the sham operation group was injected with the same volume of 0.9%NaCl.After modeling,the experimental group was given infliximab(10 mg·kg^(-1)·d^(-1))by tail vein injection for 3 days,the sham operation group and the model group were given the same amount of saline by tail vein injection every day.The nerve function of the mice was measured by corner test and mNSS score,and the water content of brain tissue was measured by dry-wet weight method.The expression levels of interleukin-1β(IL-1β)and phosphorylated c-Jun N-terminal kinase(P-JNK)in the brain of mice were detected by Western blot.Results Three days after the intervention,the left turn rates of sham ope ra tion group,model group and experimental group were(31.67±2.36)%,(13.33±2.36)%and(21.66±2.35)%;mNSS scores were 0.33±0.52,12.67±1.63 and 8.17±0.98,respectively;the cerebral water contents were(78.08±0.86)%,(81.08±0.58)%and(79.67±1.13)%,respectively;IL-1βwere 0.64±0.06,0.90±0.03 and 0.80±0.06,respectively;P-JNK were 0.31±0.09,0.57±0.02 and 0.46±0.04,respectively.Compared with the model group,the above indexes in the experimental group were statistically significant(all P<0.05).Conclusion Infliximab may be able to improve early neurological function in mice with cerebral hemorrhage by inhibiting JNK signaling pathway and reducing inflammatory reaction.

关 键 词：英夫利西单抗 脑出血 c-Jun N-末端激酶信号通路 炎症反应 

分 类 号：R965[医药卫生—药理学]