[1]姜明贺,张 鼎,朱欢欢,等.温肺降浊方对血管性痴呆大鼠海马神经元的作用机制[J].陕西中医,2024,(3):291-296.[doi:DOI:10.3969/j.issn.1000-7369.2024.03.001]
　JIANG Minghe,ZHANG Ding,ZHU Huanhuan,et al.Mechanism of Wenfei Jiangzhuo decoction on hippocampal neurons in vascular dementia rats[J].,2024,(3):291-296.[doi:DOI:10.3969/j.issn.1000-7369.2024.03.001]
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温肺降浊方对血管性痴呆大鼠海马神经元的作用机制
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2024年3期
页码:
291-296
栏目:
基础研究
出版日期:
2024-03-05

文章信息/Info

Title:
Mechanism of Wenfei Jiangzhuo decoction on hippocampal neurons in vascular dementia rats
作者:
姜明贺1; 张 鼎1; 朱欢欢2; 李方存1; 李丽琴1; 宋晨曦1; 陈 炜3; 胡跃强3
(1.广西中医药大学,广西 南宁 530001; 2.广西中医药大学附属瑞康医院,广西 南宁 530011; 3.广西中医药大学第一附属医院,广西 南宁 530023)
Author(s):
JIANG Minghe; ZHANG Ding; ZHU Huanhuan; LI Fangcun; LI Liqin; SONG Chenxi; CHEN Wei; HU Yueqiang
(Guangxi University of Traditional Chinese Medicine,Nanning 530001,China)
关键词:
血管性痴呆;  温肺降浊方;  海马神经元;  内质网应激;  沉默信息调节因子1;  CCAAT增强子结合蛋白
Keywords:
Vascular dementia;  Wenfei Jiangzhuo decoction;  Hippocampal neurons;  Endoplasmic reticulum stress;  Silent information regulator 1;  CCAAT enhancer-binding protein homologous protein
分类号:
R 277.7
DOI:
DOI:10.3969/j.issn.1000-7369.2024.03.001
文献标志码:
A
摘要:
目的:观察温肺降浊方对血管性痴呆(VaD)大鼠的作用机制。方法:建立VaD大鼠模型,随机分为模型组、西药组、温肺降浊方低剂量组、温肺降浊方中剂量组、温肺降浊方高剂量组,每组6只。另取6只大鼠设为假手术组,模型组和假手术组给予0.9%氯化钠溶液灌胃; 西药组给予尼莫地平灌胃; 温肺降浊方各剂量组给予相应剂量的温肺降浊汤灌胃。给药28 d后,采用Morris水迷宫实验评价各组大鼠学习记忆能力; HE及Nissl 染色法进行组织病理学检测。采用RT-qPCR和Western blot检测各组大鼠海马组织中沉默信息调节因子1(SIRT1)/肌醇需求酶1α(IRE1α)/剪接型X-盒结合蛋白1(XBP1S)/CCAAT增强子结合蛋白同源蛋白(CHOP)信号通路相关mRNA和蛋白表达。结果:与假手术组比较,模型组大鼠逃避潜伏期明显延长,穿越平台次数则减少。与假手术组比较,模型组大鼠海马CA1区病理损伤严重,神经元细胞明显减少,尼氏小体数量明显减少,SIRT1 mRNA和蛋白表达则降低(均P<0.01)。与假手术组比较,模型组大鼠IRE1α、XBP1S、CHOP mRNA和XBP1S、CHOP蛋白及p-IRE1α/IRE1α明显升高(均P<0.01)。与模型组比较,温肺降浊方中剂量组、温肺降浊方高剂量组、西药组大鼠逃避潜伏期缩短,穿越平台次数增加(均P<0.05)。与模型组比较,西药组和温肺降浊方各剂量组大鼠海马CA1区病理损伤减轻,神经元细胞数量增加,尼氏小体数量增加。与模型组比较,西药组和温肺降浊方各剂量组SIRT1 mRNA和蛋白表达升高,且温肺降浊方高剂量组和西药组表达较高。IRE1α、XBP1S、CHOP mRNA和XBP1S、CHOP蛋白以及p-IRE1α/IRE1α水平降低,且温肺降浊方高剂量组和西药组水平更低(均P<0.01)。结论:温肺降浊方通过激活SIRT1/IRE1α/XBP1S/CHOP信号通路,减轻VaD大鼠海马神经元区病变,从而发挥改善VaD大鼠认知能力的作用。
Abstract:
Objective:To observe effect of Wenfei Jiangzhuo decoction on vascular dementia(VaD)rats and to explore its mechanism.Methods:VaD rats model were established and randomly divided into model group,western medicine group and low-dose Wenfei Jiangzhuo group,medium-dose Wenfei Jiangzhuo group and high-dose Wenfei Jiangzhuo group,each group 6 rats.Another 6 rats were taken as sham surgery group.The model group and sham surgery group were given 0.9% sodium chloride solution.The western medicine group were given nimodipine by gavage.Each dose group of Wenfei Jiangzhuo decoction were given different doses of Wenfei Jiangzhuo decoction by gavage.After 28 days of corresponding drug intervention,Morris water maze experiment was used to evaluate learning and memory abilities of rats in each group.HE and Nissl staining methods were used for histopathological examination.RT-qPCR and Western blot were used to detect expression of mRNA and protein related to silent information regulator 1(SIRT1)/inositolrequiring enzyme 1α(IRE1α)/spliced X-box binding protein 1(XBP1S)/CCAAT enhancer-binding protein homologous protein(CHOP)signal passway in hippocanpal tissues of rats in each group.Results:Compared with the sham operation group,the escape latency of the model group were significantly prolonged and number of crossing platforms significantly decreased.The pathological damage in the CA1 area of hippocampus was severe.The number of neuronal cells and Nissl bodies were significantly reduced.The expression levels of SIRT1 mRNA and protein were significantly reduced(all P<0.01).The expression levels of IRE1α,XBP1S,CHOP mRNA and XBP1S,CHOP proteins and p-IRE1α/IRE1α were significantly increased(all P<0.01).Compared with the model group,the escape latency of the medium-dose Wenfei Jiangzhuo group,the high-dose Wenfei Jiangzhuo group and the western medicine group were significantly shortened(all P<0.05).The number of crossing platforms were significantly increased(P<0.05).Compared with the model group,the pathological damage in the CA1 area of the hippocampus of the western medicine group and each group of Wenfei Jiangzhuo decoction were reduced.The number of neuronal cells and Nissan bodies were significantly increased.Compared with the model group,SIRT1 mRNA and protein expressions were increased in the western medicine group and the Wenfei Jiangzhuo dose groups,and the expression levels were higher in the high-dose Wenfei Jiangzhuo group and the western medicine group.The levels of IRE1α,XBP1S,CHOP mRNA,XBP1S,CHOP protein and p-IRE1α/IRE1α were decreased,and the high-dose Wenfei Jiangzhuo group and the western medicine group were lower(all P<0.01).Conclusion:Wenfei Jiangzhuo decoction may activate SIRT1/IRE1α/XBP1S/CHOP signal pathway alleviates hippocampal neuronal lesions in VaD rats,thereby exerting effect of improving cognitive ability in VaD rats.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金地区基金资助项目(82260904); 广西自然科学基金资助重点项目(2019GXNSFDA245006); 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); 广西中医脑病临床研究中心项目(桂科AD20238028); 广西中医药大学研究生创新教育计划项目(YCBXJ2022012)
更新日期/Last Update: 2024-03-08