摘要
将大鼠随机分为空白组、假手术组、模型组、黄精多糖联合电针组(灌胃400 mg/kg+电针)和多奈哌齐组(灌胃0.45 mg/kg),建立血管性痴呆大鼠模型.采用Morris水迷宫实验和Nissl染色评估认知功能和神经元状况;ELISA法检测炎症IL-6、TNF-α、IL-1β和SOD、GSH-Px、LDH、MDA指标;Real-time PCR和Western blot法检测磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/核苷酸结合寡聚结构域样受体蛋白3(NLRP3)信号通路以及病理性沉积蛋白(神经细胞外β-淀粉样肽_(1-42)(Aβ_(1-42)))、微管相关蛋白(Tau)、微管相关蛋白磷酸化位点404(pTau(Ser404))指标的mRNA和蛋白表达水平;进而探讨黄精多糖联合电针调控PI3K/Akt/NLRP3通路对VD模型大鼠认知功能的影响及其机制.结果显示:与假手术组相比,模型组大鼠可见明显潜伏期延长、穿越平台位置次数和目标象限活动时间减少,且可测得LDH、MDA、IL-6、TNF-α、IL-1β的活性、水平及NLRP3、Aβ_(1-42)、Tau、p-Tau(Ser404)的mRNA、蛋白表达水平显著升高以及SOD、GSH-PX的活性及PI3K、Akt的mRNA和蛋白表达水平显著降低(P<0.05、P<0.01或P<0.001).相比模型组,黄精多糖联合电针和多奈哌齐组大鼠可见显著第4天潜伏期缩短以及次数和时间增加,且可测得LDH、MDA、IL-6、TNF-α、IL-1β的活性、水平及NLRP3、Aβ_(1-42)、Tau、p-Tau(Ser404)的mRNA、蛋白表达水平显著降低以及SOD、GSH-PX的活性及PI3K、Akt的mRNA和蛋白表达水平显著升高(P<0.05,P<0.01或P<0.001).表明黄精多糖联合电针可显著改善VD大鼠认知功能,其机制可能与调控PI3K/Akt/NLRP3通路,阻滞Aβ和Tau蛋白、炎症和氧化应激而缓解神经元损伤有关.
After being randomly distinguished into negative control group,sham operated group,model group,PSP combined with EA group(ig 400 mg/kg+EA)and donepezil group(ig O.45 mg/kg),rats were going to be converted into vascular dementia models.Learning and memory abilities,neuronal conditions,inflammation indexes(IL-6,TNF-α and IL-1β)and oxidative stress indexes(SOD,GSHPx,LDH and MDA)as well as the expressive level of mRNA and proteins of PI3K/Akt/NLRP3 signaling pathway and pathological sedimentary protein(Aβ_(1-42),Tau and p-Tau(Ser404))indexes would be measured and assessed by morris water maze test,nissl staining,ELISA methods,real-time PCR methods and Western Blot methods respectively;And then the effect and internal mechanism of PSP combined with EA on Cognitive Function in Vascular Dementia Model Rats by regulating PI3K/Akt/NLRP3 signaling pathway would be explored.The results had revealed that:compared with sham operated group,the model group rats obviously showed the longer latencies,the less times and numbers of crossing platform locations and moving in target quadrant with obviously testing the elevating activity and expressive level of mRNA and proteins of LDH,MDA,IL-6,TNF-α,IL-1β,NLRP3,Aβ_(1-42),Tau and p-Tau(Ser404)as well as the declining ones of SOD,GSH-Px,PI3K and Akt(P<0.05 or P<0.01 or P<0.001).Compared with model group,the PSP combined with EA and donepezil group rats significantly showed the shorter latencies on the 4th day and the rising times and numbers,with significantly testing the reducing activity and expressive level of mRNA and proteins of LDH,MDA,IL-6,TNF-α,IL-1β,NLRP3,Aβ_(1-42),Tau and p-Tau(Ser404)as well as the increasing ones of SOD,GSHPx,PI3K and Akt(P<0.05 or P<0.01 or P<0.001).It indicates that PSP combined with EA could significantly improve the cognitive function of VD Rats,and its mechanisms are probably relative to regulating PI3K/Akt/NLRP3 signaling pathway,antagonizing Aβ and Tau,antagonizing inflammation and oxidative stress and recovering neuronal damages.
作者
张耿超
宋娇龙
杨莉
周涛
Zhang Gengchao;Song Jiaolong;Yang Li;Zhou Tao(Department of Medicine,Hubei Minzu University,Enshi 445000,China;Department of Gastroenterology,Huanggang Hospital of Traditional Chinese Medicine&Huanggang Hospital of Traditional Chinese Medicine Affiliated to Hubei University of Chinese Medicine,Huanggang 438O0o,China;Department of Chinese Traditional Medicine,Huanggang Maternal And Child Health Hospital,Huanggang 438000,China;Department of Rehabilitation,Huanggang Hospital of Traditional Chinese Medicine&Huanggang Hospital of Traditional Chinese Medicine Affiliated to Hubei University of Chinese Medicine,Huanggang 438000,China)
出处
《南开大学学报(自然科学版)》
北大核心
2025年第5期11-17,共7页
Journal of Nankai University(Natural Sience)
基金
湖北省中医药管理局中医药青年人才项目(ZY2023Q026)
湖北省中医药管理局中医药指导性项目(ZY2023F103)。
关键词
黄精多糖
电针
血管性痴呆
认知功能障碍
PI3K/Akt/NLRP3通路
polygonatum sibiricum polysaccharides
electro acupuncture
vascular dementia
cognitive dysfunctions
PI3K/Akt/NLRP3 signaling pathway
