目的:观察化瘀通络灸对血管性痴呆大鼠Ras同源物基因组成员A(Ras homolog gene family member A,RhoA)/Rho激酶(Rho associated protein kinase, ROCK)轴突生长抑制性信号通路相关蛋白的影响,探讨其治疗血管性痴呆的机制。方法:使用Mor...目的:观察化瘀通络灸对血管性痴呆大鼠Ras同源物基因组成员A(Ras homolog gene family member A,RhoA)/Rho激酶(Rho associated protein kinase, ROCK)轴突生长抑制性信号通路相关蛋白的影响,探讨其治疗血管性痴呆的机制。方法:使用Morris水迷宫筛除贴壁、原地旋转或溺水的Wistar大鼠,将符合条件大鼠分为假手术组、造模组。假手术组暴露大鼠颈总动脉;造模组用改良的双侧颈总动脉永久结扎术制备血管性痴呆大鼠模型,术后3 d用水迷宫对大鼠进行模型鉴定,将合格者随机分为模型组、艾灸组和西药组。于鉴定次日对大鼠进行治疗,艾灸组悬灸百会、大椎、神庭,20 min/次,1次/d, 1周为1疗程,2个疗程间休息1 d,共3个疗程;西药组用吡拉西坦溶液灌胃,2次/d;假手术组、模型组行灸架固定。治疗结束,取大鼠脑组织,用免疫荧光单染法、蛋白免疫印迹法检测其脑内目的蛋白RhoA、Rho相关螺旋卷曲蛋白激酶Ⅱ(Rho protein-related curl spiral kinase-Ⅱ,ROCKⅡ)、肌球蛋白轻链磷酸化(Phosphorylation of myosin light chain, P-MLC)的阳性表达。结果:模型组大鼠海马、皮质RhoA、ROCKⅡ、P-MLC蛋白表达高于假手术组(P<0.01);艾灸组、西药组海马和皮质RhoA、ROCKⅡ、P-MLC蛋白表达较模型组低(P<0.05);艾灸组皮质ROCKⅡ蛋白表达较西药组稍低(P<0.05);艾灸组与西药组海马ROCKⅡ、海马与皮质RhoA、P-MLC蛋白表达差异无统计学意义(P>0.05)。结论:化瘀通络灸可能是通过下调RhoA/ROCK轴突生长抑制性信号通路相关蛋白的表达提高血管性痴呆大鼠的记忆力,从而发挥治疗血管性痴呆的作用。展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
