温肺降浊方对血管性痴呆大鼠线粒体外膜蛋白的影响  

Explore effect of Wenfei Jiangzhuo formula on the expression of mitochondrial outer membrane protein in vascular dementia model rats

作　　者：孙春英 张鼎 陈炜[2] 李方存 张玲[1] 周珂青 向军军[1] 胡跃强[2] SUN Chunying;ZHANG Ding;CHEN Wei;LI Fangcun;ZHANG Ling;ZHOU Keqing;XIANG Junjun;HU Yueqiang(Graduate School of Guangxi University of Traditional Chinese Medicine,Nanning 530001,China)

机构地区：[1]广西中医药大学研究生院,广西南宁530001 [2]广西中医药大学第一附属医院,广西南宁530023

出　　处：《陕西中医》2024年第11期1449-1454,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82260904);国家中医药管理局高水平重点学科建设项目(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“岐黄工程”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);广西中医药大学博士研究生创新项目(YCBXJ2023010)。

摘　　要：目的:探讨温肺降浊方对血管性痴呆(VaD)模型大鼠FUN14结构域包含蛋白1(FUNDC1)、线粒体分裂蛋白1(Fis1)、线粒体融合蛋白1(Mfn1)、线粒体融合蛋白2(Mfn2)等线粒体外膜蛋白的影响,探究本方可能的作用机制。方法:将24只大鼠随机分为假手术组、模型组、阳性对照组、温肺降浊方组,每组各6只。采用双侧颈总动脉永久性结扎法制备VaD大鼠模型,温肺降浊方组予以温肺降浊方药液,阳性对照组予以盐酸多奈哌齐。Morris水迷宫行为学测试检测各组大鼠认知水平,HE染色法检测各组大鼠海马组织病理形态,免疫荧光化学染色检测大鼠海马中FUNDC1与Fis1阳性细胞数表达,Western blotting检测FUNDC1、Fis1、Mfn1与Mfn2蛋白表达水平。结果:与假手术组相比,模型组大鼠逃避潜伏期延长、穿越平台次数减少(P<0.05),细胞破碎,核缩小,水肿化,海马中FUNDC1与Fis1阳性细胞表达量上升,FUNDC1、Fis1蛋白上升,Mfn1/2蛋白降低(P<0.05)。与模型组比较,阳性对照组和温肺降浊方组逃避潜伏期缩短、穿越平台次数增加(P<0.05),细胞核逐渐趋于正常,水肿化减少,FUNDC1与Fis1阳性细胞数及蛋白下降,Mfn1/2蛋白升高(P<0.05)。结论:温肺降浊方通过下调FUNDC1、Fis1蛋白水平,上调Mfn1/Mfn2蛋白维持线粒体动力学平衡,减轻海马神经元损伤,发挥脑保护作用。Objective:To investigate effects of Wenfei Jiangzhuo formula on the expression of mitochondrial outer membrane proteins such as FUN14 structural domain-containing protein 1(FUNDC1),mitochondrial fission protein 1(Fis1),mitochondrial fusion protein 1(Mfn1),mitochondrial fusion protein 2(Mfn2)and other mitochondrial outer membrane proteins in rats with vascular dementia(VaD)model,in order to explore the possible mechanism of action of the formula.Methods:Twenty-four rats were randomly divided into the sham-operation group,model group,positive control group,and Wenfei Jiangzhuo formula group,with six rats in each group.The rat model of VaD were prepared by permanent ligation of bilateral common carotid arteries,and the Wenfei Jiangzhuo formula group were treated with Wenfei Jiangzhuo formula liquid,and the positive control group were treated with Donepezil hydrochloride.The cognitive level of the rats was detected by Morris water maze behavioral test,the histopathological morphology of hippocampus in the groups were detected by HE staining,the expression of FUNDC1 and Fis1-positive cell number was detected by immunofluorescent staining.The expression levels of FUNDC1,Fis1,Mfn1 and Mfn2 proteins were detected by Western blotting.Results:Compared with the sham-operated group,the model group rats had longer evasion latency,reduced number of platform crossings(P<0.05),cell fragmentation,nuclear shrinkage,oedema,an increase in the expression of FUNDC1 and Fis1-positive cells in the hippocampus,increase in the expression of FUNDC1 and Fis1 proteins,and reduction in the expression of Mfn1/2 proteins(P<0.05).Compared with the model group,the positive control group and the Wenfei Jiangzhuo formula group evaded the shortening of latency and the increase in the number of crossing the plateau(P<0.05),the nuclei of the cells gradually tended to be normalised,the oedematousness was reduced,the number and protein expression of the FUNDC1 and Fis1-positive cells were decreased,and the protein expression of Mfn1/2 was elevated(P<0.0

关 键 词：血管性痴呆 线粒体动力学平衡 温肺降浊方 FUN14结构域包含蛋白1 线粒体分裂蛋白1 

分 类 号：R74[医药卫生—神经病学与精神病学]