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易亚乔,何清湖,刘检,刘林,成绍武,廖君,王国佐,谭琥,刘吉勇,陈俊炜,郭艳幸,葛金文.基于SIRT1/NF-κB炎性通路探讨加味脑泰方对血管性痴呆大鼠学习记忆及海马组织病理形态的影响[J].湖南中医药大学学报英文版,2019,39(6):684-688.[Click to copy
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| 基于SIRT1/NF-κB炎性通路探讨加味脑泰方对血管性痴呆大鼠学习记忆及海马组织病理形态的影响 |
| 易亚乔,何清湖,刘检,刘林,成绍武,廖君,王国佐,谭琥,刘吉勇,陈俊炜,郭艳幸,葛金文 |
| (湖南中医药大学, 湖南 长沙 410208;湖南中医药大学第一附属医院, 湖南 长沙 410007;河南省洛阳正骨医院, 河南 洛阳 471002) |
| 摘要: |
| 目的 探讨加味脑泰方（以下简称JWF）对血管性痴呆（vascular dementia，VD）大鼠SIRT1/NF-κB p56炎性通路的调控作用。方法 采用双侧颈总动脉结扎法（two-vessel occlusion，2-VO）复制VD大鼠模型。实验设正常组，假手术组，模型组，JWF高、中、低剂量组和奥拉西坦组，其中JWF高、中、低剂量组和奥拉西坦组分别灌胃给予JWF17.0、34.0、51.0 g/kg和奥拉西坦0.216 g/kg，其余3组灌服等容量蒸馏水，连续干预30 d。采用Morris水迷宫、HE染色分别检测大鼠学习记忆能力和海马组织病理形态变化；采用免疫组化检测沉默信息调节因子-1（silent informatio regulator-1，SIRT1）、核因子κB抑制蛋白d亚基（The nuclear factorκB inhibits theprotein subunit，IκBα）、核因子-κB（nuclear factor-kappa B，NF-κB）蛋白表达情况。结果 与正常组比较，模型组大鼠学习记忆能力显著降低（P<0.05），海马神经元变性、坏死，炎性细胞浸润增加，且SIRT1、IκBα表达下调，NF-κB p56表达上调（P<0.05）；与模型组比较，奥拉西坦组和JWF高、中剂量组大鼠学习记忆能力显著增强（P<0.05），海马组织中神经元锥体细胞排列较整齐，轮廓清晰，炎性细胞浸润显著减少，且海马组织内SIRT1、IκBα表达上调，NF-κB p56表达下调（P<0.05）。结论 JWF对血管性痴呆大鼠炎性相关信号通路SIRT1/NF-κB p56具有明显的调控作用，这可能是其保护VD大鼠海马神经元继而改善学习记忆能力的重要机制之一。 |
| 关键词: 加味脑泰方 血管性痴呆 海马组织 沉默信息调节因子-1 核因子κB抑制蛋白d亚基 核因子-κB |
| DOI：10.3969/j.issn.1674-070X.2019.06.002 |
| Received:August 14, 2018 |
| 基金项目:国家自然科学基金资助项目（81774129）；湖南省自然科学基金（2019JJ50434）；中国博士后科学基金面上项目（2018M632972）；湖南省中医药科研项目（201822）；湖南中医药大学校级科研项目（2017XJJJ09）；湖南省"双一流"学科中西医结合；湖南省教育厅科学研究项目（重点编号：18A206）。 |
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| Effects of Jiawei Naotai Formula on Learning, Memory and Pathological Morphology of Hippocampal Tissue Based on Inflammatory Pathway of SIRT1/NF-κB in Rats with Vascular Dementia |
| YI Yaqiao,HE Qinghu,LIU Jian,LIU Lin,CHEN Shaowu,LIAO Jun,WANG Guozuo,TAN Hu,LIU Jiyong,CHEN Junwei,GUO Yanxing,GE Jinwen |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;Luoyang Bone-setting Hospital of Henan Province, Luoyang, Henan 471002, China) |
| Abstract: |
| Objective To investigate the regulatory effects of Jiawei Naotai Formula (JWF) on inflammatory pathway of SIRT1/NF-κB p56 in rats with vascular dementia (VD). Methods The model of VD rats was established by bilateral common carotid artery ligation assay (two-vessel occlusion, 2-VO). There were normal group, sham operation group, model group, JWF groups of high, moderate and low dose, as well as oxiracetam group in this experiment. The JWF groups of high, moderate and low dose, and the oxiracetam group were given 17.0, 34.0 and 51.0 g/kg Jiawei Naotai Formula and 0.216 g/kg oxiracetam respectively, while the other 3 groups were given the same amount of distilled water, for 30 d of consecutive intervention. The learning and memory ability and the pathological morphology changes of hippocampal tissue of rats were detected by Morris water maze and HE staining, respectively. The protein expressions of SIRT1, IκBα and NF-κB were detected by immunohistochemistry. Results Compared with the normal group, the learning and memory ability of rats in the model group was obviously decreased (P<0.05); degeneration and necrosis of hippocampal neurons was detected and inflammatory cell infiltration was increased; the expressions of SIRT1 and IκBα were decreased, while that of NF-κB p56 was increased (P<0.05). Compared with the model group, the learning and memory ability of rats in the oxiracetam group and the JWF groups of high, moderate and low dose were notably improved (P<0.05); the neuron pyramidal cells in the hippocampal tissue were more orderly arranged with clear outlines, and inflammatory cell infiltration was obviously decreased; the expressions of SIRT1 and IκBα was increased, while that of NF-κB p56 was decreased (P<0.05). Conclusion There are significant regulatory effects of JWF on inflammatory pathway of SIRT1/NF-κB p56 in rats with vascular dementia, which may be one of the important mechanisms for protecting hippocampal neurons of VD rats and subsequently improving the learning and memory ability. |
| Key words: Jiawei Naotai Formula vascular dementia hippocampal tissue SIRT1 IκBα NF-κB |
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