首页|槲皮素缓解紫杉醇诱发外周神经病变小鼠模型的疼痛效应及其机制研究

槲皮素缓解紫杉醇诱发外周神经病变小鼠模型的疼痛效应及其机制研究

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目的 观察槲皮素对紫杉醇诱发外周神经病变小鼠模型疼痛症状、脊髓星形胶质细胞活化以及背根神经节中痛敏感瞬时感受器电位香草酸亚型1(transient receptor potential vanilloid 1,TRPV1)、嘌呤能配体门控离子通路3(purinergic ligand-gated ion channel 3,P2X3)的干预作用。方法 选取C57BL/6小鼠24只,随机分为空白组、模型组、模型+槲皮素组,每组8只。模型组与模型+槲皮素组分别注射累计剂量为8 mg/kg的紫杉醇进行造模,空白组在相应时间点注射对应溶剂。模型+槲皮素组在造模第8天开始,每天灌胃60 mg/kg的槲皮素溶液,其余两组分别给予相应体积溶剂。纤毛机械刺激针(von Frey)检测各组小鼠的机械痛痛阈,免疫荧光检测各组小鼠脊髓中星形胶质细胞的活化,免疫荧光和免疫印迹检测背根神经节中痛敏感TRPV1、P2X3的表达。结果 (1)与模型组相比,模型+槲皮素组小鼠的机械痛痛阈显著升高,疼痛症状得到明显缓解。(2)与模型组相比,模型+槲皮素组小鼠脊髓星形胶质细胞的活化明显降低,背根神经节中TRPV1、P2X3的表达显著减少(P<0。05)。结论 槲皮素能够有效缓解紫杉醇诱发外周神经病变小鼠的疼痛症状,其作用机制很可能与缓解脊髓星形胶质细胞活化以及减少背根神经节中TRPV1、P2X3表达有关。
Therapeutic effects and mechanisms of quercetin on pain responses in a mouse model of paclitaxel-induced peripheral neuropathy
Objective To observe the effect of quercetin on mechanical allodynia,astrocyte activation,and upregulation of pain-related transient receptor potential vanilloid 1(TRPV1)and P2X purinoceptor 3(P2X3)in mice with paclitaxel-induced peripheral neuropathy.Methods Twenty-four C57BL/6 mice were divided randomly into control,model,and model+quercetin groups(n=8 mice per group).Paclitaxel(total dose 8 mg/kg)was injected intraperitoneally into mice in the model and model+quercetin groups to establish the model.Mice in the control group were injected intraperitoneally with the same volume of vehicle.On day 8 after the first injection,mice in the model+quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle.Mechanical pain was measured by the von Frey test.Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence.Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot.Results(1)Compared with model group,the mechanical pain of mice in model+quercetin group were relieved.(2)Compared with model group,the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of model+quercetin group were alleviated(P<0.05).Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy.This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.

quercetinpaclitaxelpainastrocyteTRPV1P2X3

金婷、李沛奕、聂慧敏、尹诚语、潘宇霜、朱智慧、刘伯一、刘伯宇

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浙江中医药大学附属第三医院,杭州 310013

浙江中医药大学第三临床医学院针灸神经生物学实验室,杭州 310053

浙江中医药大学药学院,杭州 310053

槲皮素 紫杉醇 疼痛 星形胶质细胞 TRPV1 P2X3

国家自然科学基金浙江省自然科学基金

82305369LQ21H270004

2024

中国实验动物学报
中国实验动物学会,中国医学科学院医学实验动物研究所

中国实验动物学报

CSTPCD北大核心
影响因子:0.767
ISSN:1005-4847
年,卷(期):2024.32(9)