槲皮素促进应激颗粒G3BP1解聚改善HIV-1 gp120诱导的星形胶质细胞神经毒性  

Quercetin mitigates HIV-1 gp120-induced rat astrocyte neurotoxicity via promoting G3BP1 disassembly in stress granules

作　　者：黄鹏伟 陈洁 邹金虎 高雪锋 曹虹 HUANG Pengwei;CHEN Jie;ZOU Jinhu;GAO Xuefeng;CAO Hong(Department of Microbiology,Guangdong Provincial Key Laboratory of Tropical Disease Research//School of Public Health,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学公共卫生学院//广东省热带病研究重点实验室//微生物学系,广东广州510515

出　　处：《南方医科大学学报》2025年第2期304-312,共9页Journal of Southern Medical University

基　　金：国家自然科学基金(82172259);广东省自然科学基金(2023A1515012231,2024A1515010606);南方医科大学公卫学院院长基金(GW202329)。

摘　　要：目的探究槲皮素(QC)在HIV-1 gp120诱导的星形胶质细胞神经毒性中的抑制作用及机制。方法分离原代星形胶质细胞作为细胞模型,将细胞分为对照组、QC组、HIV-1 gp120组和梯度剂量QC治疗组。免疫荧光法观察应激颗粒(SGs)形成。氧化应激标志物水平和相关蛋白表达水平分别使用特异性试剂盒和Western blotting测定。HIV-1 gp120转基因小鼠(Gp120 tgm)灌胃50 mg/kg QC治疗4周。随后进行行为学评价实验,取血清进行氧化应激指标检测,取脑组织进行免疫组化染色与Western blotting分析。结果体外实验中,QC减少星形胶质细胞中的SGs(P<0.05),提高抗氧化指标水平(P<0.05),同时降低氧化物质水平(P<0.001),并且上调与SGs解聚相关的蛋白水平(P<0.05)。在体内,QC改善了Gp120 tgm的认知功能障碍表现,缓解氧化应激(P<0.05),促进SGs解聚相关蛋白表达(P<0.05)。结论QC通过抑制氧化应激,促进SGs解聚蛋白表达和SGs解聚,减轻HIV-1 gp120诱导的星形胶质细胞毒性和改善认知功能。提示QC具备作为HIV-1相关神经认知障碍的治疗药物的潜力。Objective To explore the effect of quercetin for mitigating HIV-1 gp120-induced astrocyte neurotoxicity and its underlying mechanism.Methods Primary rat astrocytes were isolated and treated with quercetin,HIV-1 gp120,or gradient concentrations of quercetin combined with HIV-1 gp120.The formation of stress granules(SGs)in the treated cells was observed with immunofluorescence assay,and the levels of oxidative stress markers and protein expressions were measured using specific assay kits and Western blotting.HIV-1 gp120 transgenic mice were treated with quercetin(50 mg/kg)by gavage for 4 weeks,and the changes in cognitive functions and oxidative stress levels were examined by behavioral assessments,oxidative stress index analysis in serum,and immunohistochemical and Western blotting of the brain tissue.Results In primary rat astrocytes,treatment with quercetin significantly reduced HIV-1 gp120-induced SG formation,increased the levels of antioxidant indexes,decreased the levels of oxidative substances,and up-regulated protein level associated with SG depolymerization.In the transgenic mouse models,quercetin obviously improved the cognitive function of the rats,reduced oxidative stress levels,and promoted the expression of proteins associate with SG depolymerization in the brain tissues.Conclusion Quercetin mitigates HIV-1 gp120-induced astrocyte neurotoxicity and cognitive function impairment by inhibiting oxidative stress,enhancing expressions of SG depolymerization-related proteins,and promoting SG disassembly,suggesting the value of quercetin as a potential therapeutic agent for neuroprotection in HIV-associated neurocognitive disorders.

关 键 词：槲皮素 星形胶质细胞 应激颗粒 氧化应激 HIV-1 gp120 

分 类 号：R285.5[医药卫生—中药学]