虾青素对慢性氧乐果中毒认知障碍小鼠的神经保护作用

发布时间：2018-05-20 04:21

本文选题：虾青素 + 慢性　；参考：《青岛大学》2017年硕士论文

【摘要】：目的:探讨虾青素(astaxanthin,AST)对慢性氧乐果中毒认知障碍小鼠的神经保护作用及可能的机制。方法:55只昆明小鼠随机挑选8只作为对照组,其余47只氧乐果5mg/Kg皮下注射,连续染毒4周建立慢性氧乐果中毒认知障碍模型,将造模成功的40小鼠随机分为模型组8只,AST组8只,依达拉奉(edaravone,EDA)组8只,氯化锂(lithium chloride,Li Cl)组8只,AST+Li Cl组8只。AST组将AST用花生油稀释至浓度为1mg/ml,每天按50μg/g/d给予灌胃,连续4周;EDA组:EDA每只给予3mg/kg腹腔注射,每日一次,连续4周;Li Cl组:将Li Cl每只给予2mmol/kg腹腔注射,隔日一次,连续4周;AST+Li Cl组:将AST用花生油稀释至浓度为1mg/ml,每天按50μg/g/d给予灌胃后,Li Cl每只给予2mmol/kg腹腔注射,隔日一次,连续4周;模型组与对照组:每天按50μg/g/d给予灌胃等体积的花生油,连续4周。应用Morris水迷宫检测小鼠的学习记忆能力;ELISA法检测脑组织活性氧(ROS)含量,比色法检测超氧化物歧化酶(SOD)与谷胱甘肽过氧化物酶(GSH-PX)活性;HE染色、刚果红染色及原位末端标记(TUNEL)染色观察小鼠海马组织形态学变化及细胞凋亡水平;免疫组织化学染色和Western blot检测p-PI3K、p-Akt、p-GSK3β与p-CREB在海马组织内的分布和表达水平。结果:模型组小鼠慢性氧乐果中毒后,学习记忆能力下降;脑组织海马区ROS含量升高,SOD和GSH-PX活性下降(均P0.05),神经元损伤明显,海马区及周围血管内壁出现明显的淀粉样物质沉积,神经细胞凋亡数量较对照组显著增多(P0.05),p-PI3K、p-Akt、p-GSK3β与p-CREB表达较对照组显著降低(均P0.05)。AST组小鼠学习记忆能力较模型组明显改善(P0.05),ROS含量较模型组明显降低,SOD和GSH-PX活性显著升高(均P0.05),海马区神经元损伤减轻,淀粉样物质的沉积和凋亡细胞数较模型组明显减少(P0.05),p-PI3K、p-Akt、p-GSK3β与p-CREB表达较模型组显著升高(均P0.05)。结论:AST通过上调Akt/GSK3β/CREB信号通路的磷酸化水平,对慢性氧乐果中毒认知障碍小鼠起到神经保护作用。
[Abstract]:Objective: to investigate the neuroprotective effect of astaxanthinum astaxanthin (AST) on cognitive impairment mice with chronic omethoate poisoning and its possible mechanism. Methods eight of 55 Kunming mice were randomly selected as control group, the other 47 mice were subcutaneously injected with omethoate 5mg/Kg, and the cognitive impairment model of chronic omethoate poisoning for 4 Zhou Jianli was administered continuously. 40 mice were randomly divided into model group (n = 8), Edaravone group (n = 8) and lithium chloride group (n = 8). The AST was diluted with peanut oil to a concentration of 1 mg / ml. In the control group, 3mg/kg was injected intraperitoneally once a day for 4 weeks, and every 2mmol/kg was injected intraperitoneally once every other day for 4 weeks. AST was diluted to 1 mg / ml with peanut oil for 4 weeks. After 50 渭 g/d per day, Li Cl was injected intraperitoneally with 2mmol/kg once every other day for 4 weeks. Model group and control group were given 50 渭 g/d daily with peanut oil of the same volume. 4 weeks in a row. Morris water maze was used to detect the learning and memory ability of mice. The content of Ros in brain tissue was detected by Elisa, and the activities of SOD and GSH-PX were detected by colorimetry. Congo red staining and in situ end labeling Tunel staining were used to observe the morphological changes and apoptosis level of hippocampal tissue in mice, and the distribution and expression of p-PI3Knp-Aktna-p-GSK3 尾 and p-CREB in hippocampal tissue were detected by immunohistochemical staining and Western blot. Results: after chronic omethoate poisoning, the learning and memory ability of model group mice decreased, the ROS content in hippocampus increased and the activities of sod and GSH-PX decreased (both P0.05A, P 0.05). Amyloid deposition was observed in the hippocampal area and the surrounding vascular wall. The number of neuronal apoptosis was significantly increased than that of the control group. The expression of P0.05, p-PI3KGN, p-Aktna-p-GSK3 尾 and p-CREB in the P0.05).AST group was significantly lower than that in the control group (all the mice in the P0.05).AST group significantly improved the learning and memory ability of the model group compared with the model group, and the Ros content in the model group was significantly lower than that in the model group. The injury of hippocampal neurons was alleviated. Compared with the model group, the number of apoptotic cells and the deposition of amyloid decreased significantly (P 0.05), and the expression of p-PI3K ~ (3) K _ (3) P _ (I) ~ (3) K _ (p-AktN) -GSK _ (3 尾) and p-CREB increased significantly compared with the model group (all P 0.05). Conclusion by upregulating the phosphorylation level of Akt/GSK3 尾 -CREB signaling pathway, brain aspartate plays a neuroprotective role in cognitive impairment mice with chronic omethoate poisoning.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R595.4;R747.9

【相似文献】