摘要
目的:观察温肺降浊方对血管性痴呆(VaD)模型大鼠细胞外调节蛋白激酶(ERK1/2)信号通路的影响,探讨其治疗VaD可能的相关作用机制。方法:将雄性SD大鼠随机分为假手术组和模型组(等体积0.9%氯化钠溶液灌胃),温肺降浊方低、中、高剂量组(1.5、3、6 ml剂量灌胃)。观察造模后大鼠水迷宫评分和HE病理变化,免疫组化、RT-qPCR和Western blot检测海马组织中ERK1/2、钙蛋白酶(Calpain)、Bcl-2关联死亡启动子重组蛋白(Bad)、B淋巴细胞瘤-xl(Bcl-xl)蛋白和mRNA表达情况。结果:与假手术组相比,模型组和温肺降浊方各剂量组大鼠逃避潜伏期延长、穿越平台次数缩短(P<0.05),海马组织形态稀疏、水肿及核缩小;海马组织ERK1/2、Calpain、Bad蛋白和mRNA表达升高(P<0.05),Bcl-xl蛋白和mRNA表达下降(P<0.05)。与模型组比较,温肺降浊方高剂量组大鼠逃避潜伏期缩短、穿越平台次数增加(P<0.05),海马组织形态逐渐紧密、水肿减少,数量增多;海马组织ERK1/2、Calpain、Bad蛋白和mRNA表达下降(P<0.05),Bcl-xl蛋白和mRNA表达升高(P<0.05)。结论:血管性痴呆可能与大鼠海马中的ERK1/2、Calpain、Bad蛋白升高及Bcl-xl蛋白降低有关,温肺降浊方可以抑制VaD大鼠海马中的ERK1/2通路激活,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。
Objective:To observe the effect of Wenfei Jiangzhuo prescription on ERK1/2 signaling pathway in Vascular dementia(VaD) model rats,and to explore the possible mechanism of its therapeutic effect on VaD.Methods:Male SD rats were randomly divided into the following groups:the sham operation group and the model group(equal volume of saline gavage),the low-dose group of Wenfei Jiangzhuo prescription,the medium-dose group of Wenfei Jiangzhuo prescription and the high-dose group of Wenfei Jiangzhuo prescription(1.5,3 and 6 ml doses by gavage).The water maze score and HE pathological changes of rats after modeling were observed,and ERK1/2,Calpain,Bad,Bcl-xl protein and mRNA expressions in hippocampal tissues were observed by immunohistochemistry,RT-qPCR and Western blot.Results:Compared with the sham-operated group,rats in the model group and each dose group of Wenfei Jiangzhuo prescription had prolonged evasion latency and shortened the number of crossing platforms(P<0.05),and the morphology of hippocampal tissues was sparse,edematous,and the nuclei were shrunken;the expression of ERK1/2,Calpain,and Bad proteins and mRNAs in hippocampal tissues was elevated(P<0.05) and the expression of Bcl-xl proteins and mRNAs was decreased(P<0.05);compared with the model group,rats in the high-dose group of Wenfei Jiangzhuo prescription had shorter evasion latency and increased the number of crossing platforms(P<0.05),the morphology of hippocampal tissues was progressively tighter,the edema was reduced,and the number of hippocampal tissues was increased;the hippocampal tissues had decreased in the expression of ERK1/2,Calpain,and Bad proteins and mRNAs(P<0.05),and the expression of Bcl-xl proteins and mRNAs was elevated(P<0.05).Conclusion:Vascular dementia may be related to the elevation of ERK1/2,Calpain and Bad proteins and the decrease of Bcl-xl protein in the hippocampus of rats.Wenfei Jiangzhuo prescription can inhibit the activation of ERK1/2 pathway in the hippocampus of rats with VaD,reduce the apoptosis of neuronal cells,slow down the progression of the disease,and improve learning and memory ability of rats with vascular dementia.
作者
宋晨曦
张鼎
胡芷涵
姜明贺
李方存
胡跃强
SONG Chenxi;ZHANG Ding;HU Zhihan;JIANG Minghe;LI Fangcun;HU Yueqiang(Guangxi University of Chinese Medicine,Nanning 530001,China)
出处
《陕西中医》
CAS
2024年第2期171-175,186,共6页
Shaanxi Journal of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(82260904)
广西中医脑病临床研究中心项目(桂科AD20238028)
广西高等学校高水平创新团队及卓越学者计划项目(桂教人才202006)
广西中医药大学博士研究生创新项目(YCBXJ2023010)。
关键词
血管性痴呆
温肺降浊方
ERK1/2信号通路
海马组织
大鼠
Vascular dementia
Wenfei Jiangzhuo prescription
ERK1/2 signaling pathway
Hippocampal tissue
Rats
