基于NLRP3-NF-κB-MMP-9通路探讨白藜芦醇对铝暴露致大鼠颅脑神经损伤的保护作用

职业与健康 ›› 2025, Vol. 41 ›› Issue (11): 1469-1476.

基于NLRP3-NF-κB-MMP-9通路探讨白藜芦醇对铝暴露致大鼠颅脑神经损伤的保护作用

张波, 石勇

重庆市荣昌区人民医院神经外科,重庆 402460

收稿日期:2024-08-02 修回日期:2024-08-19 出版日期:2025-06-01 发布日期:2025-12-12
通信作者: 石勇,副主任医师,E-mail：1548121935@qq.com
作者简介:张波,男,主治医师,主要从事颅脑神经损伤救治工作。
基金资助:
重庆市卫生健康委员会医学科研项目（2023047）

Exploring the protective effect of resveratrol on aluminum induced cranial nerve injury in rats based on the NLRP3-NF-κB-MMP-9 pathway

ZHANG Bo, SHI Yong

Department of Neurosurgery, Chongqing Rongchang District People's Hospital, Chongqing 402460, China

Received:2024-08-02 Revised:2024-08-19 Online:2025-06-01 Published:2025-12-12
Contact: SHI Yong,Associate chief physician,E-mail：1548121935@qq.com

摘要/Abstract

摘要： 目的基于NOD样受体家族含吡啶结构域3蛋白（nod-like receptor family pyrin domain containing 3,NLRP3）-核因子 kappa-beta（nuclear factor kappa-beta,NF-κB）-基质金属蛋白酶 9（metalloproteinase 9,MMP-9）通路,探讨白藜芦醇对铝暴露致大鼠颅脑神经损伤的保护作用。方法 40只成年大鼠分为正常对照组、铝暴露组、白藜芦醇低、高剂量组（100、200 mg/kg）。铝暴露组、白藜芦醇低高剂量组大鼠通过暴露三氯化铝以建立颅脑神经功能损伤模型,铝暴露期间,白藜芦醇低高剂量组大鼠每日予以白藜芦醇灌胃干预,正常对照组和铝暴露组给予等体积生理盐水。试验结束后测定神经功能指标、颅脑血脑屏障渗漏水平、颅脑组织神经细胞凋亡水平、颅脑组织NLRP3、NF-κB、基质金属蛋白酶 9（metalloproteinase 9,MMP-9）mRNA蛋白表达水平、颅脑组织炎症因子肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、白介素-1β（interleukin-1 beta,IL-1β）、一氧化氮合酶（nitric oxide synthase,iNOS）水平。结果与正常对照组比较,铝暴露组神经行为评分、游泳距离、逃避潜伏期、颅脑血脑屏障渗漏率、颅脑神经细胞凋亡指数、颅脑组织NLRP3、NF-κB、MMP-9 mRNA蛋白水平（0.86±0.09 vs 3.58±0.29、0.75±0.08 vs 4.20±0.22、0.97±0.06 vs 4.12±0.18,0.29±0.05 vs 1.74±0.19、0.38±0.07 vs 1.86±0.18、0.34±0.08 vs 1.79±0.20）、颅脑组织炎症因子TNF-α、IL-1β、iNOS水平升高,穿过原始平台位置的次数降低,差异均有统计学意义（均P<0.05）。与铝暴露组相比,白藜芦醇低、高剂量组神经行为评分、游泳距离、逃避潜伏期、颅脑血脑屏障渗漏率、颅脑神经细胞凋亡指数、颅脑组织NLRP3、NF-κB、MMP-9 mRNA蛋白水平（3.58±0.29 vs 2.68±0.19、1.62±0.13,4.20±0.22 vs 2.55±0.17、1.72±0.17,4.12±0.18 vs 3.14±0.13、2.01±0.10;1.74±0.19 vs 1.04±0.13、0.73±0.10,1.86±0.18 vs 1.53±0.16、1.02±0.10,1.79±0.20 vs 1.27±0.18、0.74±0.11）、颅脑组织炎症因子TNF-α、IL-1β、iNOS水平降低,穿过原始平台位置的次数升高,差异均有统计学意义（均P<0.05）。与白藜芦醇低剂量组相比,白藜芦醇高剂量组神经行为评分、游泳距离、逃避潜伏期、颅脑血脑屏障渗漏率、颅脑神经细胞凋亡指数、颅脑组织NLRP3、NF-κB、MMP-9 mRNA蛋白水平、颅脑组织炎症因子TNF-α、IL-1β、iNOS水平降低,穿过原始平台位置的次数升高,差异均有统计学意义（均P<0.05）。结论白藜芦醇对铝暴露对大鼠颅脑神经损伤具有明显治疗作用,其机制与白藜芦醇抑制铝暴露诱导的大鼠颅脑NLRP3、NF-κB、MMP-9 mRNA蛋白表达进而抑制NLRP3-NF-κB-MMP-9通路的激活有关。

关键词: NOD样受体家族含吡啶结构域3蛋白, 核因子 kappa-beta, 基质金属蛋白酶 9, 白藜芦醇, 铝, 颅脑神经损伤

Abstract: Objective To explore the protective effect of resveratrol on aluminum induced cranial nerve injury in rats based on the nod-like receptor family pyrin domain containing 3（NLRP3）- nuclear factor kappa-beta（NF-κB）- metalloproteinase 9（MMP-9） pathway. Methods Totally 40 adult rats were divided into a normal control group,an aluminum exposure group,and resveratrol low-dose and high-dose groups（100 and 200 mg/kg）. Rats in the aluminum exposure group and the low-dose and high-dose resveratrol group were exposed to aluminum trichloride to establish a model of cranial nerve function injury. During the exposure period,the rats in the low-dose and high-dose resveratrol groups were given daily resveratrol gavage intervention,while the normal control group and the aluminum exposure group were given an equal volume of normal saline. After the experiment,neurological function indicators,blood-brain barrier leakage level,neuronal apoptosis levels in brain tissue,brain tissue NLRP3,NF-κB,MMP-9 mRNA protein expression levels,tumor necrosis factor-α（TNF-α）,interleukin-1 beta（IL-1β）,nitric oxide synthase（iNOS） levels. Results Compared with the normal control group,the aluminum exposure group showed an increase in neurobehavioral scores,swimming distance,escape latency,blood-brain barrier leakage rate,apoptosis index of cranial nerve cells,NLRP3,NF-κB,and MMP-9 mRNA protein levels in cranial tissue（0.86 ±0.09 vs 3.58±0.29,0.75± 0.08 vs 4.20±0.22,0.97± 0.06 vs 4.12±0.18, 0.29± 0.05 vs 1.74± 0.19,0.38±0.07 vs 1.86± 0.18,0.34±0.08 vs 1.79±0.20）, as well as an increase in levels of inflammatory factors TNF-α, IL-1β, and iNOS in cranial tissue,and a decrease in the number of crossing the original platform position,and the differences were statistically significant（all P<0.05）. Compared with the aluminum exposure group,resveratrol low-dose and high-dose groups neurobehavioral scores,swimming distance,escape latency,blood-brain barrier leakage rate,apoptosis index of cranial nerve cells,cranial tissue NLRP3,NF-κB,MMP-9 mRNA protein levels（3.58±0.29 vs 2.68±0.19,1.62±0.13,4.20±0.22 vs 2.55±0.17,1.72±0.17,4.12±0.18 vs 3.14±0.13,2.01±0.10;1.74±0.19 vs 1.04±0.13,0.73±0.10,1.86±0.18 vs 1.53±0.16,1.02±0.10,1.79±0.20 vs 1.27±0.18,0.74±0.11）,cranial tissue inflammatory factor TNF-α,IL-1β,and iNOS levels decreased,and the number of crossing the original platform position increased,the differences were statistically significant（allP <0.05）. Compared with the resveratrol low-dose group, the resveratrol high-dose group showed a decrease in neurobehavioral scores,swimming distance,escape latency,blood-brain barrier leakage rate,apoptosis index of cranial nerve cells,cranial tissue NLRP3,NF-κB,MMP-9 mRNA protein levels and cranial tissue inflammatory factors TNF-α,IL-1β,iNOS levels,an increase in the number of crossing the original platform position,and the differences were statistically significant（all P<0.05）. Conclusion Resveratrol has a significant therapeutic effect on aluminum exposure induced cranial nerve injury in rats,and its mechanism is related to the inhibition of NLRP3,NF-κB,and MMP-9 mRNA protein expression induced by aluminum exposure,thereby inhibiting the activation of the NLRP3-NF-κB-MMP-9 pathway.

Key words: NLRP3, NF-κB, MMP-9, Resveratrol, Aluminum, Cranial nerve injury

张波, 石勇. 基于NLRP3-NF-κB-MMP-9通路探讨白藜芦醇对铝暴露致大鼠颅脑神经损伤的保护作用. [J]职业与健康, 2025, 41(11): 1469-1476.

ZHANG Bo, SHI Yong. Exploring the protective effect of resveratrol on aluminum induced cranial nerve injury in rats based on the NLRP3-NF-κB-MMP-9 pathway. [J]OCCUPATION AND HEALTH, 2025, 41(11): 1469-1476.

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