摘要
目的通过观察温肺降浊方对血管性痴呆(vascular dementia,VaD)模型大鼠PINK1/Parkin信号通路的影响,阐发其治疗VaD可能的相关作用机制。方法将SPF级雄性SD大鼠随机分为:假手术组和模型组(等体积生理盐水灌胃)、3-MA抑制剂组(3-甲基腺嘌呤,100 nmol/μL,6μL/只,海马CA1区)、西药组(多奈哌齐片0.45 mg·kg^(-1)·d^(-1)灌胃)、中药组(温肺降浊方5 g/kg灌胃)。观察模型建立后大鼠的水迷宫评分、HE病理变化和免疫荧光表达,qRT-PCR和Western Blotting检测大鼠海马组织中PINK1、Parkin、p62、Ubl蛋白及mRNA表达情况。结果与假手术组比,模型组大鼠逃避潜伏期明显延长,穿越平台次数明显减少,差异有统计学意义(P<0.05)。海马CA1区细胞形态不规则,细胞数量较少、排列散乱,海马组织中PINK1、Parkin、p62、Ubl蛋白和mRNA表达升高(P<0.05);与模型组比,3-MA抑制剂组、西药组和中药组大鼠逃避潜伏期缩短、穿越平台次数增加,差异均有统计学意义(P<0.05),海马CA1区细胞数量逐渐增多、排列紧密;海马组织PINK1、Parkin、p62、Ubl蛋白和mRNA表达降低(P<0.05)。结论血管性痴呆可能与PINK1/Parkin通路的过度激活有关,温肺降浊方可以下调该通路中相关蛋白的表达,减少神经细胞凋亡,延缓疾病进展,改善血管性痴呆大鼠的学习记忆能力,发挥脑保护作用。
Objective To elucidate the possible mechanism of action of Wenfei Jiangzhuo Formula(温肺降浊方)on PINK1/Parkin signaling pathway in vascular dementia(VaD)model rats by observing its effect on VaD.Methods Male SD rats of SPF grade were randomly divided into the sham-operated group and model group(the equal volume of saline by gavage),3-methyladenine(3-MA)inhibitor group(100 nmol/μL,6μL/only,hippocampal CA1 area),western medicine group(donepezil tablets,0.45 mg·kg^(-1)·d^(-1),by gavage)and traditional Chinese medicine group(Wenfei Jiangzhuo Formula,5 g/kg,by gavage).The water maze score,HE pathological changes and immunofluorescence expression of rats after model establishment were observed.The qRT-PCR and Western Blotting were used to detect the expressions of PINK1,Parkin,p62 and Ubl proteins and mRNAs in the hippocampal tissues of rats.Results Compared with those in the sham-operated group,the escape latency of rats in the model group was significantly longer,and the number of crossing platforms was significantly reduced,with statistically significant differences(P<0.05).The cell morphology of hippocampal CA1 area was irregular,the number of cells was small and scattered,and the expressions of PINK1,Parkin,p62 and Ubl protein and mRNAs in hippocampal tissues were elevated(P<0.05).Compared with those in the model group,the evasion latency was shortened and the number of traversing platforms was increased in the 3-MA inhibitor group,the western medicine group and the traditional Chinese medicine group,and the differences were statistically significant(P<0.05).The number of cells in CA1 area of hippocampus gradually increased and tightly arranged.The expressions of PINK1,Parkin,p62 and Ubl protein and mRNAs in hippocampal tissue decreased(P<0.05).Conclusion Vascular dementia may be related to the over-activation of PINK1/Parkin pathway.Wenfei Jiangzhuo Formula can down-regulate the expressions of related proteins in this pathway,reduce the apoptosis of neuronal cells,delay the disease progression,improve the learning and memory ability of rats with vascular dementia,and plays a cerebroprotective role.
作者
宋晨曦
张鼎
陈炜
周珂青
孙春英
秦红玲
杨书慧
张玲
胡跃强
SONG Chenxi;ZHANG Ding;CHEN Wei;ZHOU Keqing;SUN Chunying;QIN Hongling;YANG Shuhui;ZHANG Ling;HU Yueqiang(Guangxi University of Chinese Medicine,Nanning 530200,Guangxi,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Guangxi Nanning 530023,Guangxi,China)
出处
《辽宁中医杂志》
北大核心
2026年第2期182-186,I0005,共6页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金项目(82260904)
国家中医药管理局高水平重点学科-中医内科学(ZYYZDXK-2023166)
广西中医脑病临床研究中心项目(桂科AD20238028)
广西中医药大学“歧黄工程”高层次人才团队项目(202410)
广西中医药重点学科建设项目(GZXK-Z-20-13)。
