MSK1/CREB信号轴的激活与丁苯酞抑制大鼠脑出血后神经元凋亡的相关性  

Correlation between activation of MSK1/CREB signaling axis and inhibition of neuronal apoptosis by dl-3-n-butylphthalide after intracerebral hemorrhage in rats

作　　者：张海龙 植剑文 杨寒 王泊浩 叶静倩 宁波 ZHANG Hailong;ZHI Jianwen#;YANG Han;WANG Bohao;YE Jingqian;NING Bo(Department of Neurosurgery,Guangzhou Red Cross Hospital Affiliated to Jinan University,Guangzhou 510220,Guangdong,China)

机构地区：[1]暨南大学附属广州红十字会医院神经外科,广东广州510220

出　　处：《暨南大学学报（自然科学与医学版）》2024年第1期1-10,共10页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：广州市科学技术局市校联合项目(202201020035)。

摘　　要：目的:探讨丁苯酞(NBP)通过丝裂原和应激激活激酶-环磷腺苷效应元件结合蛋白(MSK1-CREB)信号轴对脑出血(ICH)后神经元凋亡的抑制机制。方法:通过Ⅶ型胶原酶尾状核内注入法建立大鼠ICH模型,分别设对照组、假手术组(Sham)、ICH+NBP组、ICH+生理盐水(NS)组。使用改良大鼠神经功能缺损评分(mNSS)评估神经功能,采用干-湿重比较法测量脑组织含水率,通过蛋白印迹和免疫荧光分析检测血肿周围组织中半胱氨酸蛋白酶-3(Caspase-3)、B淋巴细胞瘤-2因子(Bcl-2)、环磷腺苷效应元件结合蛋白(CREB)和丝裂原和应激激活激酶1(MSK1)的表达水平。结果:NBP治疗可显著改善脑出血后大鼠的神经功能缺损,减轻脑水肿,同时抑制Caspase-3的表达并增加Bcl-2、CREB和MSK1的表达。结论:丁苯酞可通过MSK1-CREB信号轴抑制大鼠脑出血后神经元凋亡,改善神经功能和减轻脑水肿。Objective:To investigate the inhibitory mechanism of dl-3-n-butylphthalide(NBP)on neuronal apoptosis after intracerebral hemorrhage(ICH)through the mitogen and stress activated protein kinase1-cAMP-response element binding protein(MSK1-CREB)signaling axis.Methods:A rat model of ICH was established using collagenase typeⅦinjection into the caudate nucleus.Groups were set up as follows:control,sham operation(Sham),ICH+NBP and ICH+normal saline(NS).Neurological function was assessed using the modified neurological severity score(mNSS).Brain water content was measured by the wet-dry weight method.Expression levels of Caspase-3,B-cell lymphoma-2(Bcl-2),cAMP-response element binding protein(CREB),and mitogen and stress activated protein kinase1(MSK1)in the perihematoma tissue were detected by Western blotting and immunofluorescence analysis.Results:NBP treatment significantly improved neurological deficits after ICH in rats,alleviated brain edema,and inhibited the expression of Caspase-3 while increasing the expression of Bcl-2,CREB,and MSK1.Conclusion:NBP inhibits neuronal apoptosis after ICH in rats through the MSK1-CREB signaling axis,a theoretical basis for the application of NBP in the treatment of ICH.

关 键 词：脑出血(ICH) 神经元 凋亡 丁苯酞 丝裂原和应激激活激酶1(MSK1) 

分 类 号：R651.1[医药卫生—外科学]