基于RIP1/RIP3/MLKL通路探讨芝麻素对阿尔茨海默病大鼠学习记忆能力及神经炎症的影响*

doi:10.3870/j.issn.1672-0741.25.03.013

摘要/Abstract

摘要： 目的基于RIP1/RIP3/MLKL通路探讨芝麻素对阿尔茨海默病(AD)大鼠学习记忆能力及神经炎症的影响。方法注射淀粉样蛋白-β1-42(Aβ1-42)溶液建立AD大鼠模型,并随机分为AD组、芝麻素低剂量(芝麻素-低,80 mg/kg)组、芝麻素高剂量(芝麻素-高,160 mg/kg)组、吡拉西坦(500 mg/kg)组、芝麻素-高+rRIP1(8 μg/kg)组,并以注射生理盐水的10只大鼠为空白组。干预后,检测各种大鼠行为学以评估空间学习和记忆能力;ELISA法检测各组海马组织中Aβ1-42、白介素(IL)-1β、肿瘤坏死因子(TNF)-α、IL-6水平;制备海马组织切片,检测病理形态、神经元凋亡及胶质纤维酸性蛋白(GFAP)表达;Western blot检测RIP1/RIP3/MLKL通路相关蛋白表达。结果与空白组比较,AD组逃避潜伏期、Aβ1-42、IL-1β、TNF-α、IL-6、神经元凋亡、GFAP表达、RIP1、RIP3、MLKL表达增加,穿越平台次数降低(均P<0.05);与AD组相比,芝麻素-低组、芝麻素-高组、吡拉西坦组逃避潜伏期、Aβ1-42、IL-1β、TNF-α、IL-6、神经元凋亡、GFAP表达、RIP1、RIP3、MLKL表达降低,穿越平台次数增加(均P<0.05);与芝麻素-高组相比,芝麻素-高+rRIP1组逃避潜伏期、Aβ1-42、IL-1β、TNF-α、IL-6、神经元凋亡、GFAP表达、RIP1、RIP3、MLKL表达增加,穿越平台次数减少(均P<0.05)。结论芝麻素抑制RIP1/RIP3/MLKL通路减轻AD大鼠神经炎症,提高学习记忆能力。

关键词: 阿尔茨海默病, 学习记忆能力, 神经炎症, 芝麻素, RIP1/RIP3/MLKL通路

Abstract: Objective To investigate the effects of sesamin on learning,memory and neuroinflammation in Alzheimer's disease(AD)rats based on RIP1/RIP3/MLKL pathway.Methods AD rats models were established by injecting amyloid beta 1-42(Aβ1-42)solution.The rats were randomly divided into AD group,low-dose sesamin(sesamin-low,80 mg/kg)group,high-dose sesamin(sesamin-high,160 mg/kg)group,piracetam(500 mg/kg)group,and sesamin-high+rRIP1(8 μg/kg)group.Ten rats injected with normal saline served as the blank group.After intervention,behavioral tests were conducted to evaluate spatial learning and memory abilities in the rats.ELISA was used to detect the levels of Aβ1-42,interleukin(IL)-1β,tumor necrosis factor(TNF)-α,and IL-6.Tissue sections were prepared to examine pathological morphology,neuronal apoptosis,and glial fibrillary acidic protein(GFAP)expression.Western blot was performed to detect the expression of proteins realted to the RIP1/RIP3/MLKL pathway.Results Compared with blank group,AD group showed increased escape latency,elevated levels of Aβ1-42,IL-1β,TNF-α,and IL-6,increased neuronal apoptosis,enhanced GFAP expression,and upregulated expression of RIP1,RIP3,and MLKL,along with reduced platform crossing frequency(all P<0.05).Compared with AD group,sesamin-low group,sesamin-high group,and piracetam group exhibited decreased escape latency,reduced levels of Aβ1-42,IL-1β,TNF-α,and IL-6,decreased neuronal apoptosis,diminished GFAP expression,downregulated expression of RIP1,RIP3,and MLKL,and increased platform crossing frequency(all P<0.05).Compared with sesamin-high group,sesamin-high+rRIP1 group shouwed increased escape latency,elevated levels of Aβ1-42,IL-1β,TNF-α,and IL-6,increased neuronal apoptosis,enhanced GFAP expression,upregulated expression of RIP1,RIP3,and MLKL,and reduced platform crossing frequency(all P<0.05).Conclusion Sesamin alleviates neuroinflammation and improves learning and memory abilities in AD rats by inhibiting the RIP1/RIP3/MLKL pathway.

Key words: Alzheimer's disease, learning and memory abilities, neuroinflammation, sesamin, RIP1/RIP3/MLKL pathway

中图分类号:

R749.16
R741

高月娟, 王慧然, 李佳欣, 金春花, 李海燕. 基于RIP1/RIP3/MLKL通路探讨芝麻素对阿尔茨海默病大鼠学习记忆能力及神经炎症的影响^*[J]. 华中科技大学学报（医学版）, 2026, 55(4): 534-540.

Gao Yuejuan, Wang Huiran, Li Jiaxin, et al. Exploring the Effects of Sesamin on Learning and Memory Abilities and Neuroinflammation inAlzheimer's Disease Rats Based on RIP1/RIP3/MLKL Pathway[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(4): 534-540.

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基于RIP1/RIP3/MLKL通路探讨芝麻素对阿尔茨海默病大鼠学习记忆能力及神经炎症的影响^*

Exploring the Effects of Sesamin on Learning and Memory Abilities and Neuroinflammation inAlzheimer's Disease Rats Based on RIP1/RIP3/MLKL Pathway

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