摘要
目的探讨盐酸多奈哌齐联合脑脉通治疗老年痴呆的作用机制。方法选择无特定病原体(SPF)级健康雄性SD大鼠50只作为研究对象,随机分为空白组、模型组、盐酸多奈哌齐组、脑脉通组与联合用药组,每组10只。除空白组外,其余各组采用皮下注射D-半乳糖和聚集肽Aβ25~35制备老年痴呆大鼠模型。建模成功后,盐酸多奈哌齐组给予盐酸多奈哌齐0.85 mg/(kg·d)灌胃,脑脉通组给予脑脉通复方制剂1.50 g/(kg·d)灌胃,联合用药组同时给予盐酸多奈哌齐和脑脉通灌胃,空白组和模型组给予生理盐水2.50 mL/(kg·d)灌胃,持续灌胃8周。分别于给药前、给药1周、3周、5周和8周时测定血清糖萼损伤标志物(Syndecan-1、硫酸乙酰肝素)水平。于给药8周后处死各组大鼠,观察各组大鼠脑组织形态,检测脑组织匀浆中白细胞介素(IL)-6、IL-1及肿瘤坏死因子-α(TNF-α)含量和脑源性神经营养因子(BDNF)、神经生长因子(NGF)蛋白表达水平。结果与模型组比较,盐酸多奈哌齐组、脑脉通组和联合用药组脑组织海马神经细胞排列恢复一定的规律性,数量增多。与模型组比较,盐酸多奈哌齐组、脑脉通组与联合用药组炎性因子水平均降低(P<0.05或P<0.01)。与模型组比较,盐酸多奈哌齐组和脑脉通组BDNF、NGF表达水平差异均无统计学意义(P>0.05),联合用药组BDNF、NGF表达水平升高(P<0.01)。与模型组比较,盐酸多奈哌齐组和脑脉通组在灌胃5周时,联合用药组在灌胃3周时,血清Syndecan-1和硫酸乙酰肝素水平降低(P<0.05)。结论盐酸多奈哌齐与脑脉通联合用药对老年痴呆大鼠的改善作用可能是通过保护血管内皮糖萼、抑制炎症反应,进而修复海马神经组织和提高神经营养因子水平实现的。
Objective To explore the mechanism of donepezil hydrochloride combined with Naomaitong in the treatment of senile dementia.Methods Fifty healthy male Sprague-Dawley(SD)rats were selected and randomly divided into blank group,model group,donepezil hydrochloride group,Naomaitong group,and combination drug group,with 10 rats in each group.Except the blank group,the rats in other groups were injected subcutaneously with D-galactose and aggregate peptide Aβ25~35 to prepare rat models of Alzheimer′s disease.After successful modeling,the rats in donepezil hydrochloride group were given intragastric administration of donepezil hydrochloride 0.85 mg/(kg·d),the rats in Naomaitong group were given intragastric administration of Naomaitong 1.50 g/(kg·d),the rats in combination drug group were given intragastric administration of donepezil hydrochloride and Naomaitong,and the rats in blank group and model group were administered 2.50 mL/(kg·d)saline for 8 weeks.Serum glycocalyx damage markers(Syndecan-1,heparan sulfate)were measured before administration,at 1 week,3 weeks,5 weeks,and 8 weeks administration.Rats in each group were sacrificed after 8 weeks of administration,and the morphology of the brain tissue in each group was observed.The levels of interleukin-6(IL-6),interleukin-1(IL-1),tumor necrosis factor-α(TNF-α),brain derived neurotrophic factor(BDNF),and nerve growth factor(NGF)protein in the brain tissue homogenate were measured.Results Compared with model group,the hippocampus nerve cell arrangement in the brain tissue of donepezil hydrochloride group,Naomaitong group,and combination drug group recovered to a certain regularity and increased in number.Compared with model group,the levels of inflammatory factors in donepezil hydrochloride group,Naomaitong group,and combination drug group reduced(P<0.05 or P<0.01).Compared with model group,the expression levels of BDNF and NGF in donepezil hydrochloride group and Naomaitong group did not significantly change(P>0.05),and the expression levels of BDNF and NGF in combination drug group increased(P<0.01).Compared with model group,the levels of serum Syndecan-1 and heparan sulfate decreased in donepezil hydrochloride group and Naomaitong group at 5 weeks administration,and decreased in combination group at 3 weeks administration(P<0.05).Conclusion The improved effect of combined use of donepezil hydrochloride and Naomaitong on senile dementia rats may be achieved by protecting vascular endothelial glycocalyx,inhibiting inflammatory response,and then repairing hippocampus nerve tissue and neurotrophic factors.
作者
王静
邹荣成
汪捷
罗兵
WANG Jing;ZOU Rongcheng;WANG Jie;LUO Bing(Nanjing Lishui People′s Hospital,Zhongda Hospital Lishui Branch,Southeast University,Nanjing 221200,Jiangsu,China)
出处
《中西医结合心脑血管病杂志》
2021年第2期253-257,共5页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
江苏大学医学临床科技发展基金(No.JLY20180210)。
关键词
老年痴呆
盐酸多奈哌齐
脑脉通
糖萼
脑源性神经营养因子
神经生长因子
实验研究
senile dementia
donepezil hydrochloride
Naomaitong
glycocalyx
brain-derived neurotrophic factor
nerve growth factor
experiment research
作者简介
通讯作者:邹荣成,E-mail:zouldr@163.com。
