摘要
目的研究积雪草苷调控Toll样受体9(TLR9)/髓样分化因子88(MyD88)/核因子κB p65(NF-κB p65)对脑动脉瘤(CA)大鼠动脉瘤壁炎症反应的影响。方法建立CA大鼠模型,随机分为模型组、积雪草苷(50 mg/kg)组、CpG-ODN(TLR9激活剂,4 mg/kg)组、积雪草苷(50 mg/kg)+CpG-ODN(4 mg/kg)组,每组12只,另取12只大鼠设为假手术组。分组处理后,检测大鼠脑血管壁厚度和动脉瘤体积,苏木精-伊红(HE)染色检测脑血管组织形态,酶联免疫吸附法(ELISA)检测大鼠脑血管组织和血清中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平,Western blot检测大鼠脑血管组织TLR9、MyD88及核内NF-κB p65蛋白水平。结果与假手术组相比,模型组大鼠血管壁明显变厚,脑动脉血管隆起,呈瘤样改变等CA症状,脑血管壁厚度、动脉瘤体积、脑血管组织和血清中IL-1β及TNF-α水平、脑血管组织TLR9、MyD88及核内NF-κB p65蛋白水平明显升高(P<0.05)。与模型组相比,积雪草苷组大鼠CA症状变轻,脑血管壁厚度、动脉瘤体积、脑血管组织和血清中IL-1β及TNF-α水平、脑血管组织TLR9、MyD88及核内NF-κB p65蛋白水平降低(P<0.05);而CpG-ODN组大鼠CA症状加重,脑血管壁厚度、动脉瘤体积、脑血管组织和血清中IL-1β及TNF-α水平、脑血管组织TLR9、MyD88及核内NF-κB p65蛋白水平升高(P<0.05)。使用积雪草苷和CpG-ODN联合处理,较积雪草苷组大鼠CA症状加重,脑血管壁厚度、动脉瘤体积、脑血管组织和血清中IL-1β及TNF-α水平、脑血管组织TLR9、MyD88及核内NF-κB p65蛋白水平升高(P<0.05)。结论积雪草苷可通过下调TLR9/MyD88/NF-κB p65通路蛋白表达减轻CA大鼠脑动脉血管组织的炎症,减小瘤体。
Aim To study the effect of asiaticoside on the inflammatory response in the aneurysm wall of rats with cerebral aneurysm by down-regulating TLR9/MyD88/NF-κB p65.Methods The CA rat model was established,they were randomly divided into model group,asiaticoside(50 mg/kg)group,CpG-ODN(TLR9 activator,4 mg/kg)group,asiaticoside(50 mg/kg)+CpG-ODN(4 mg/kg)group,with 12 rats in each group,another 12 rats were set as sham operation group.After group treatment,the thickness of the cerebral vessel wall and the volume of the aneurysm in the rats were measured,the morphology of cerebrovascular tissue was detected by HE staining,the levels of IL-1βand TNF-αin rat brain blood vessels and serum were detected by enzyme-linked immunosorbent assay(ELISA),the protein levels of TLR9,MyD88,and nuclear NF-κB p65 in rat brain vascular tissues were detected by Western blot.Results Compared with the sham operation group,the vascular wall became thicker,the cerebral arteries bulged and showed tumorlike changes and other CA symptoms,the brain blood vessel wall thickness,aneurysm volume,cerebrovascular tissue and serum IL-1βand TNF-αlevels,cerebrovascular tissue TLR9,MyD88 levels and nuclear NF-κB p65 protein level increased significantly in the model group(P<0.05).Compared with the model group,the symptoms of CA became lighter,the brain blood vessel wall thickness,aneurysm volume,cerebrovascular tissue and serum IL-1βand TNF-αlevels,cerebro-vascular tissue TLR9,MyD88 levels and nuclear NF-κB p65 protein level decreased significantly in the asiaticoside group(P<0.05);but the symptoms of CA were aggravated,the brain blood vessel wall thickness,aneurysm volume,cerebrovas-cular tissue and serum IL-1βand TNF-αlevels,cerebrovascular tissue TLR9,MyD88 levels and nuclear NF-κB p65 pro-tein level increased significantly in the CpG-ODN group(P<0.05).Compared with the asiaticoside group,the symptoms of CA were aggravated,the brain blood vessel wall thickness,aneurysm volume,cerebrovascular tissue and serum IL-1βand TNF-αlevels,cerebrovas
作者
张波
义艳
王俊
王永
ZHANG Bo;YI Yan;WANG Jun;WANG Yong(Department of Neurology,Suining First People's Hospital,Suining,Sichuan 629000,China)
出处
《中国动脉硬化杂志》
CAS
2021年第10期851-856,共6页
Chinese Journal of Arteriosclerosis
基金
四川省中医药管理局科学技术研究专项课题任务(2020JC0122)。
