基于Keap1/Nrf2/HO-1信号通路研究利舒康胶囊对高原缺氧小鼠学习记忆障碍的改善作用
投稿时间:2023-03-06  修订日期:2023-09-22  点此下载全文
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作者单位邮编
孟盼盼 兰州理工大学 730050
杨中铎 兰州理工大学 730050
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
中文摘要:[摘 要] 目的:基于Keap1/Nrf2/HO-1信号通路探讨利舒康胶囊对高原缺氧小鼠学习记忆障碍的改善作用。方法:将 60只Balb/C雄性小鼠随机分为正常对照组、缺氧模型组、红景天胶囊组:400mg/(kg.d)、利舒康胶囊低、中、高剂量组:400mg/(kg.d)、600mg/(kg.d)、800mg/(kg.d),每组10只。各组灌胃给药7d,第4d给药结束后,正常对照组饲养于当地海拔(1500m),其余各组置于低压低氧动物实验舱模拟高原海拔7500m缺氧3d,期间每天灌胃给药一次,正常对照组和缺氧模型组给予生理盐水,末次给药后1h,采用八臂迷宫检测小鼠在模拟高原缺氧状态下空间记忆能力;HE染色观察小鼠脑组织海马区的形态学变化;Western blot 法检测海马组织中Keap1/Nrf2/HO-1信号通路蛋白含量变化及凋亡相关蛋白含量变化。结果:与正常对照组相比,缺氧模型组小鼠空间记忆能力明显损伤(P<0.01);HE染色观察小鼠海马神经元损伤严重; Keap1蛋白含量及凋亡相关蛋白Bax、Caspase-3含量均上升(P<0.01);Nrf2、HO-1及凋亡相关蛋白Bcl-2含量下降(P<0.01)。与缺氧模型组相比,利舒康胶囊高剂量组小鼠在八臂迷宫行为学实验中错误率显著降低(P<0.05,P<0.01);HE染色观察神经元细胞排列整齐,细胞形态较好;Keap1蛋白含量及凋亡相关蛋白Bax、Caspase-3含量均下降(P<0.01);Nrf2、HO-1及凋亡相关蛋白Bcl-2含量上升(P<0.01)。结论:高原缺氧可以导致小鼠氧化应激损伤、诱导凋亡相关基因的表达,从而加重了小鼠认知功能的障碍;利舒康胶囊能有效改善缺氧引起的小鼠学习记忆障碍,其作用机制可能与调控Keap1/Nrf2/HO-1信号通路、降低凋亡有关。
中文关键词:高原缺氧  利舒康胶囊  学习记忆能力  Keap1/Nrf2/HO-1通路  形态学变化  凋亡。
 
Study on the Effect of Lishukang Capsule on Learning and Memory Impairment in Mice with High Altitude Hypoxia Based on Keap1/Nrf2/HO-1 Signal Pathway
Abstract:[Abstract] Objective: Study on the Effect of Lishukang Capsule on Learning and Memory Impairment in Mice with High Altitude Hypoxia Based on Keap1/Nrf2/HO-1 Signal Pathway.Methods: Sixty male Balb/C mice were randomly divided into normal control group, hypoxia model group, Rhodiola capsule group :400mg/(kg.d), low, medium and high dose groups of Lishukang capsule: 400mg/(kg.d), 600mg/(kg.d), 800mg/(kg.d)), with 10 mice in each group. The normal control group was fed at the local altitude (1500m) after 7 days of intragastric administration in each group, and the rest groups were fed at the low pressure and hypoxia animal experimental cabin to simulate the altitude of 7500m for hypoxia for 3 days. During this period, the normal control group and the hypoxia model group were given physiological saline once a day, and 1 hour after the last administration,Eight arm maze was used to test the spatial memory ability of mice under simulated high altitude hypoxia; HE staining was used to observe the morphological changes of hippocampus in mice; Western blot was used to detect the changes of protein content of Keap1/Nrf2/HO-1 signal pathway and apoptosis related protein in hippocampus of mice.Results: Compared with the normal control group, the spatial memory ability of mice in the hypoxia model group was significantly impaired (P<0.01); HE staining showed that hippocampal neurons in mice were seriously injured; the content of brain tissue Keap1 protein and apoptosis related protein Bax and Caspase-3 increased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 decreased (P<0.01). Compared with the hypoxia model group, the error rate of mice in the high dose group of Lishukang capsule in the eight arm maze behavior experiment was significantly reduced (P<0.05, P<0.01); HE staining showed that the neurons were arranged orderly and the cell morphology was good; the content of Keap1 protein and apoptosis related protein Bax and Caspase-3 decreased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 increased (P<0.01).Conciusion: High altitude hypoxia can lead to oxidative stress injury in mouse brain tissue and induce the expression of apoptosis related genes, thus aggravating the cognitive dysfunction of mice; Lishukang capsule can effectively improve the learning and memory impairment of mice caused by hypoxia, and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signal pathway and reducing apoptosis.
keywords:high altitude hypoxia  Lishukang capsule  Learning and memory ability  Keap1 / Nrf2 / HO-1 signaling pathway  Morphological changes  Apoptosis.
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