山莨菪碱通过抑制ATF6通路介导的内质网应激和血管内皮细胞凋亡延缓颅内动脉瘤疾病进展  

Anisodamine delayed the progression of intracranial aneurysm by inhibiting ATF6 pathway mediated endoplasmic reticulum stress and vascular endothelial cell apoptosis

作　　者：陈兵 冯浩 邹成功 唐辉 Chen Bing;Feng Hao;Zou Chenggong;Tang Hui(Department of Neurosurgery,the Nanchong Central Hospital,Sichuan 637000,China)

机构地区：[1]南充市中心医院神经外科,四川637000

出　　处：《脑与神经疾病杂志》2025年第2期103-110,共8页Journal of Brain and Nervous Diseases

基　　金：四川青年创新科研课题计划项目(Q20035)。

摘　　要：目的探讨山莨菪碱(anisodamine)延缓颅内动脉瘤(IA)疾病进展的疗效及其分子机制。方法在体实验,30只小鼠随机分为3组:对照组、假手术组和模型组,每组10只小鼠。模型组小鼠建立IA小鼠模型。体外细胞实验,使用原代人脐静脉内皮细胞(HUVECs)进行,分为3组:对照组、脂多糖LPS组和LPS+山莨菪碱组。Western blot法检测小鼠Willis环动脉瘤血管壁组织和HUVECs细胞内质网应激相关蛋白质因子和细胞凋亡相关蛋白质因子的表达水平。ELISA法测定上述组织和细胞上清液中TNF-α和IL-1β的水平。结果在体实验,与假手术组相比,模型组小鼠Willis环动脉瘤血管壁组织中内质网应激相关蛋白质因子转录激活因子-6(ATF6(p50))、磷酸化-丝/苏氨酸蛋白激酶(p-AKT)、核转录因子κB(NF-κB(p-p65))亚基水平上调(P<0.05),ATF6(p90)水平下调(P<0.05)。细胞凋亡相关蛋白质因子凋亡相关蛋白(Bax)、裂解-半胱天冬酶-3(cleaved Caspase-3)水平上调(P<0.05),B细胞淋巴瘤相关蛋白-2(Bcl-2)水平下调(P<0.05)。AKT和NF-κB(p65)亚基水平在两组间比较差异无统计学意义(P>O.05)。肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的水平上调(P<0.05)。与对照组相比,假手术组上述检测指标差异无统计学意义(P>0.05)。体外HUVECs细胞实验,与对照组相比,LPS组ATF6(p50)、p-AKT、NF-κB(p-p65)亚基水平上调(P<0.05),ATF6(p90)水平下调(P<0.05)。细胞凋亡相关蛋白质因子Bax、cleaved Caspase-3水平上调(P<0.05),Bcl-2水平下调(P<0.05)。AKT和NF-κB(p65)亚基水平在两组间比较差异无统计学意义(P>0.05)。细胞上清液中TNF-α和IL-1β的水平上调(P<0.05)。与脂多糖组相比,脂多糖+山莨菪碱组逆转了上述检测指标的水平(P<0.05)。结论山莨菪碱可抑制ATF6通路介导的内质网应激和血管内皮细胞凋亡,或许可延缓IA疾病进展。Objective To investigate the effects and molecular mechanisms of anisodamine on delaying the progression of intracranial aneurysms(IA).Methods In vivo experiment,30 mice were randomly divided into 3 groups:control group,sham group and model group,with 10 mice each.IA mouse model was established as model group.In vitro cell experiment,primary human umbilical vein endothelial cells(HUVECs)were divided into 3 groups:control group,lipopolysaccharide(LPS)group and LPS+anisodamine group.Western blot assay was used to detect the expression levels of endoplasmic reticulum stress related protein factors and apoptosisrelated protein factors in mice Willis ring aneurysms and HUVECs cells.ELISA was used to detect the levels of TNF-αand IL-1βin the above tissues and cell supernatants.Results In vivo,compared with sham group,in model group the levels of endoplasmic reticulum stress-related protein factor activating transcription factor-6(ATF6(p50)),phosphorylated AKT serine/threonine kinase(p-AKT),nuclear factor kappa B(NF-κB(p-p65))ubunits in the vascular tissues of Willis ring aneurysms were up-regulated(P<0.05),ATF6(p90)levels was down-regulated(P<0.05).Apoptosis-related protein factor BCL2 associated X(Bax)and cleaved Caspase-3 levels were up-regulated(P<0.05),the level of B cell leukemia/lymphoma 2(Bcl-2)was down-regulated(P<0.05).There were no significant difference in AKT and NF-κB(p65)subunit levels between the two groups(P>0.05).The levels of tumour necrosis factor alpha(TNF-α)and interleukin 1 beta(IL-1β)were up-regulated(P<0.05).Compared with the control group,there was no significant difference in the above detection indexes in the sham group(P>0.05).In vitro HUVECs cell experiments,compared with control group,in LPS group cells ATF6(p50),p-AKT,NF-κB(p-p65)ubunits were up-regulated(P<0.05),ATF6(p90)levels was down-regulated(P<0.05).Bax and cleaved Caspase-3 levels were up-regulated(P<0.05),Bcl-2 was down-regulated(P<0.05).There were no significant difference in AKT and NF-κB(p65)subunit levels between the t

关 键 词：颅内动脉瘤 血管内皮细胞 内质网应激 细胞凋亡 山莨菪碱 

分 类 号：R743[医药卫生—神经病学与精神病学]