Liu Lan, Zhang Yongcang, Tang Liang, Zhong Hua, Danzeng Dunzhu, Liang Cuiting, Liu Shanling
Medical College, Tibet University, Lhasa, Tibet 850000, China.
Department of Obstetrics & Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Evid Based Complement Alternat Med. 2021 Feb 27;2021:8879014. doi: 10.1155/2021/8879014. eCollection 2021.
Inflammatory factors play an important role in the pathogenesis of Alzheimer's disease (AD). 25 (BM25) has been suggested to have protective effects in the central nervous system. However, the effect of BM25 on AD has not been determined. This study aims to investigate the neuroprotective effect of BM25 in AD. A total of 40 AD model mice were randomly assigned to the following five groups ( = 8 per group): the AD + NS group, the AD + donepezil group, and three AD + BM25 groups treated with either 58.39 mg/kg (AD + BM25-L), 116.77 mg/kg (AD + BM25-M), or 233.54 mg/kg BM25 (AD + BM25-H). The Morris water maze test was performed to assess alterations in spatial learning and memory deficits. Nissl staining was performed to detect Nissl bodies and neuronal damage. The expression of IL-1 and TNF- was evaluated by ELISA. The protein expression of P-P38, P38, P-IB, caspase 1, COX2, and iNOS was determined by western blotting. The expression of A, p-Tau, and CD11b was measured by immunohistochemistry. The mRNA expression levels of IL-1, TNF-, COX2, and iNOS were measured by qRT-PCR. Spatial memory significantly improved in the AD + BM25-M and AD + BM25-H groups compared with the AD + NS group ( < 0.05). The expression of A and p-Tau significantly decreased in the AD + BM25-M and AD + BM25-H groups ( < 0.05). The neuron density and hierarchy and number of pyramidal neurons significantly increased in the AD + BM25-M and AD + BM25-H groups ( < 0.05). In addition, the expression levels of CD11b, IL-1, TNF-, COX2, iNOS, caspase 1, p-IB, and p-P38 significantly decreased in the AD + BM25-M and AD + BM25-H groups ( < 0.05). In conclusion, our findings suggest that BM25 may exert anti-inflammatory and neuroprotective effects in AD model mice by suppressing the activity of microglia and inhibiting the phosphorylation of IB and p38 MAPK.
炎症因子在阿尔茨海默病（AD）的发病机制中起重要作用。已有研究表明25（BM25）在中枢神经系统中具有保护作用。然而，BM25对AD的影响尚未确定。本研究旨在探讨BM25在AD中的神经保护作用。将40只AD模型小鼠随机分为以下五组（每组n = 8）：AD + NS组、AD + 多奈哌齐组以及三个分别用58.39 mg/kg（AD + BM25-L）、116.77 mg/kg（AD + BM25-M）或233.54 mg/kg BM25处理的AD + BM25组（AD + BM25-H）。进行莫里斯水迷宫试验以评估空间学习和记忆缺陷的改变。进行尼氏染色以检测尼氏体和神经元损伤。通过酶联免疫吸附测定（ELISA）评估白细胞介素-1（IL-1）和肿瘤坏死因子（TNF-）的表达。通过蛋白质印迹法测定磷酸化P38（P-P38）、P38、磷酸化IκB（P-IκB）、半胱天冬酶1（caspase 1）、环氧化酶2（COX2）和诱导型一氧化氮合酶（iNOS）的蛋白表达。通过免疫组织化学法测定淀粉样蛋白（Aβ）、磷酸化tau蛋白（p-Tau）和CD11b的表达。通过实时定量聚合酶链反应（qRT-PCR）测定IL-1、TNF-、COX2和iNOS的mRNA表达水平。与AD + NS组相比，AD + BM25-M组和AD + BM25-H组的空间记忆明显改善（P < 0.05）。AD + BM25-M组和AD + BM25-H组中Aβ和p-Tau的表达明显降低（P < 0.05）。AD + BM25-M组和AD + BM25-H组中锥体神经元的神经元密度、层次结构和数量明显增加（P < 0.05）。此外，AD + BM25-M组和AD + BM25-H组中CD11b、IL-1、TNF-、COX2、iNOS、caspase 1、P-IκB和P-P38的表达水平明显降低（P < 0.05）。总之，我们的研究结果表明，BM25可能通过抑制小胶质细胞的活性并抑制IκB和p38丝裂原活化蛋白激酶（MAPK）的磷酸化，在AD模型小鼠中发挥抗炎和神经保护作用。
