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
张海龙 1植剑文 1杨寒 1王泊浩 1叶静倩 1宁波1
作者信息
- 1. 暨南大学 附属广州红十字会医院 神经外科,广东 广州 510220
- 折叠
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.
Abstract
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 type Ⅶ injection 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)Key words
intracerebral hemorrhage(ICH)/neuron/apoptosis/dl-3-n-butylphthalide/mitogen and stress activated protein kinase1(MSK1)引用本文复制引用
基金项目
广州市科技局市校联合项目(202201020035)
出版年
2024
NETL
NSTL
万方数据