槲皮素通过抑制MIP-1α/CCR1/CCR5信号通路减轻大鼠带状疱疹后神经痛的机制

doi:10.11958/20221587

天津医药 ›› 2024, Vol. 52 ›› Issue (3): 256-260.doi: 10.11958/20221587

槲皮素通过抑制MIP-1α/CCR1/CCR5信号通路减轻大鼠带状疱疹后神经痛的机制

田佳玉(), 冯丹^△(), 胡焓, 张书力, 童胜雄, 李少军

武汉市第一医院疼痛科（邮编430000）

收稿日期:2023-09-27 修回日期:2023-12-06 出版日期:2024-03-15 发布日期:2024-03-13
通讯作者: ^△E-mail：ht3bxv@163.com
作者简介:田佳玉（1989），女，主治医师，主要从事疼痛方面研究。E-mail：az8mjy@163.com
基金资助:
湖北省卫生健康委员会科研项目(WX19C31);湖北省卫生健康委员会科研项目(WX21Q41)

Mechanism of quercetin alleviating postherpetic neuralgia in rats by inhibiting MIP-1α/CCR1/CCR5 signaling pathway

TIAN Jiayu(), FENG Dan^△(), HU Han, ZHANG Shuli, TONG Shengxiong, LI Shaojun

Department of Pain, Wuhan First Hospital, Wuhan 430000, China

Received:2023-09-27 Revised:2023-12-06 Published:2024-03-15 Online:2024-03-13
Contact: ^△E-mail: ht3bxv@163.com

田佳玉, 冯丹, 胡焓, 张书力, 童胜雄, 李少军. 槲皮素通过抑制MIP-1α/CCR1/CCR5信号通路减轻大鼠带状疱疹后神经痛的机制[J]. 天津医药, 2024, 52(3): 256-260.

TIAN Jiayu, FENG Dan, HU Han, ZHANG Shuli, TONG Shengxiong, LI Shaojun. Mechanism of quercetin alleviating postherpetic neuralgia in rats by inhibiting MIP-1α/CCR1/CCR5 signaling pathway[J]. Tianjin Medical Journal, 2024, 52(3): 256-260.

摘要/Abstract

摘要：

目的探讨槲皮素（Que）对大鼠带状疱疹后神经痛（PHN）及趋化因子配体3（CCL3，即MIP-1α）/C-C趋化因子受体（CCR）1/CCR5信号通路的影响。方法将60只大鼠分为对照组（Con组）、PHN组、L-Que组（30 mg/kg）、M-Que组（60 mg/kg）、H-Que组（120 mg/kg）以及H-Que+MIP-1α组（120 mg/kg Que+0.4 μg/kg重组MIP-1α）。检测各组大鼠机械痛阈值（PWT）、热痛阈值（TWL）；试剂盒检测外周组织液腺苷、腺嘌呤核糖核苷酸（AMP）、腺苷二磷酸（ADP）以及脊髓背角样本肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平；通过HE染色观察脊髓背角病理切片；免疫荧光染色检测脊髓背角小胶质细胞活化情况；Western blot检测MIP-1α/CCR1/CCR5信号通路蛋白表达。结果 PHN组脊髓背角组织出现破裂现象，神经束排列混乱，炎性细胞浸润、水肿，神经元轻微萎缩现象。与Con组相比，PHN组PWT值、腺苷、AMP、ADP水平降低（P<0.05），TWL值、TNF-α、IL-1β水平、Iba1阳性小胶质细胞数量以及MIP-1α、CCR1、CCR5蛋白水平均升高（P<0.05）；Que治疗后，大鼠神经束排列杂乱现象有所改善，炎性细胞浸润减少，神经元萎缩现象减轻；与PHN组相比，L-Que组、M-Que组、H-Que组的PWT值、腺苷、AMP、ADP水平升高（P<0.05），TWL值、TNF-α、IL-1β水平、Iba1阳性小胶质细胞数量以及MIP-1α、CCR1、CCR5蛋白水平均降低（P<0.05），且Que作用效果呈剂量依赖性；与H-Que组相比，H-Que+MIP-1α组的PWT值、腺苷、AMP、ADP水平降低（P<0.05），TWL值、TNF-α、IL-1β水平、Iba1阳性小胶质细胞数量以及MIP-1α、CCR1、CCR5蛋白水平均升高（P<0.05）。结论 Que可能通过抑制MIP-1α/CCR1/CCR5信号通路减轻大鼠炎症反应，进而减轻PHN。

关键词: 槲皮素, 神经痛, 带状疱疹后, 趋化因子CCL3, 受体, CCR1, 受体, CCR5

Abstract:

Objective To investigate the impact of quercetin (Que) on postherpetic neuralgia (PHN) and chemokine ligand 3 (CCL3, namely MIP-1α)/C-C chemokine receptor 1 (CCR1)/C-C chemokine receptor 5 (CCR5) signaling pathway in rats. Methods Sixty rats were divided into the control group (Con), the PHN group (model group), the L-Que (30 mg/kg) group, the M-Que (60 mg/kg) group, the H-Que (120 mg/kg) group and the H-Que+pathway activator MIP-1α (120 mg/kg Que+0.4 μg/kg recombinant MIP-1α) group. The mechanical paw withdrawal threshold (PWT) and thermal pain threshold (TWL) of rats were detected in each group. The kit was used to detect adenosine, Adenine ribonucleotide (AMP), adenosine diphosphate (ADP) and tumor necrosis factor in spinal dorsal horn samples- α (TNF-α), and interleukin-1 β (IL-1 β) levels in spinal dorsal horn samples. HE staining was applied to observe the pathological sections of spinal dorsal horn. Immunofluorescence staining was used to detect the activation of microglia in spinal dorsal horn. Western blot assay was applied to detect MIP-1α/CCR1/CCR5 signaling pathway protein expression. Results In the PHN group, the dorsal horn of the spinal cord was ruptured, the arrangement of nerve bundles was disordered, and inflammatory cell infiltration, edema, and slight atrophy of neurons appeared. Compared with the Con group, the PWT value, adenosine, AMP and ADP levels were obviously decreased in the PHN group (P<0.05), and TWL value, TNF-α, IL-1β levels, the number of Iba1-positive microglia, MIP-1α, CCR1 and CCR5 protein levels were obviously increased (P<0.05). After treatment with Que, the disordered arrangement of nerve bundles was improved, the infiltration of inflammatory cells was reduced, and the phenomenon of neuronal atrophy disappeared. Compared with the PHN group, the PWT value, adenosine, AMP and ADP levels were obviously increased in the L-Que group, the M-Que group and the H-Que group (P<0.05). TWL value, TNF-α and IL-1β levels, the number of Iba1-positive microglia, and MIP-1α, CCR1 and CCR5 protein levels were obviously decreased (P<0.05). The effect of Que was dose dependent. Compared with the H-Que group, PWT value, adenosine, AMP and ADP levels were obviously decreased in the H-Que+MIP-1α group (P<0.05), and TWL value, TNF-α, IL-1β levels, the number of Iba1 positive microglia, MIP-1α, CCR1 and CCR5 protein levels were obviously increased (P<0.05). Conclusion Que may reduce the inflammatory response in rats by inhibiting the MIP-1α/CCR1/CCR5 signaling pathway, thereby reducing PHN.

Key words: Quercetin, neuralgia, postherpetic, chemokine CCL3, receptors, CCR1, receptors, CCR5

中图分类号:

R752.12

图/表 7

参考文献 23

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组别	PWT/g	TWL/s
Con组	25.64±2.56	10.08±1.00
PHN组	10.35±1.04^a	28.96±2.95^a
L-Que组	14.76±1.43^b	23.89±2.35^b
M-Que组	19.54±1.94^bc	17.76±1.76^bc
H-Que组	23.97±2.40^bcd	11.46±1.54^bcd
H-Que+MIP-1α组	11.24±1.26^e	27.00±2.71^e
F	72.742^＊＊	82.339^＊＊

组别	PWT/g	TWL/s
Con组	25.64±2.56	10.08±1.00
PHN组	10.35±1.04^a	28.96±2.95^a
L-Que组	14.76±1.43^b	23.89±2.35^b
M-Que组	19.54±1.94^bc	17.76±1.76^bc
H-Que组	23.97±2.40^bcd	11.46±1.54^bcd
H-Que+MIP-1α组	11.24±1.26^e	27.00±2.71^e
F	72.742^＊＊	82.339^＊＊

组别	腺苷	AMP	ADP
Con组	46.26±4.66	9.54±0.96	29.12±2.92
PHN组	10.98±1.10^a	3.01±0.31^a	6.65±0.67^a
L-Que组	21.78±2.18^b	4.69±0.46^b	13.54±1.36^b
M-Que组	32.65±3.22^bc	6.89±0.69^bc	20.87±2.09^bc
H-Que组	43.23±4.40^bcd	8.98±0.89^bcd	28.34±2.85^bcd
H-Que+MIP-1α组	11.95±1.19^e	4.03±0.41^e	7.33±0.73^e
F	143.547^＊＊	98.655^＊＊	151.134^＊＊

组别	腺苷	AMP	ADP
Con组	46.26±4.66	9.54±0.96	29.12±2.92
PHN组	10.98±1.10^a	3.01±0.31^a	6.65±0.67^a
L-Que组	21.78±2.18^b	4.69±0.46^b	13.54±1.36^b
M-Que组	32.65±3.22^bc	6.89±0.69^bc	20.87±2.09^bc
H-Que组	43.23±4.40^bcd	8.98±0.89^bcd	28.34±2.85^bcd
H-Que+MIP-1α组	11.95±1.19^e	4.03±0.41^e	7.33±0.73^e
F	143.547^＊＊	98.655^＊＊	151.134^＊＊

组别	TNF-α/（μg/L）	IL-1β/（μg/L）	Iba1阳性小胶质细胞数量/个
Con组	16.43±1.66	40.78±4.77	200.21±2.03
PHN组	50.64±5.05^a	96.34±9.65^a	402.54±4.03^a
L-Que组	41.91±4.13^b	83.86±8.35^b	335.78±3.36^b
M-Que组	30.78±3.12^bc	70.53±7.06^bc	270.43±2.70^bc
H-Que组	18.74±1.88^bcd	54.21±5.44^bcd	203.65±2.04^bcd
H-Que+MIP-1α组	48.28±4.83^e	90.02±9.11^e	391.23±3.91^e
F	96.163^＊＊	48.592^＊＊	4 960.725^＊＊

槲皮素通过抑制MIP-1α/CCR1/CCR5信号通路减轻大鼠带状疱疹后神经痛的机制

Mechanism of quercetin alleviating postherpetic neuralgia in rats by inhibiting MIP-1α/CCR1/CCR5 signaling pathway

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参考文献 23

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组别	MIP-1α	CCR1	CCR5
Con组	1.06±0.11	0.37±0.36	0.68±0.07
PHN组	2.78±0.28^a	1.98±0.20^a	2.53±0.25^a
L-Que组	2.13±0.21^b	1.46±0.16^b	1.97±0.20^b
M-Que组	1.66±0.17^bc	0.93±0.09^bc	1.37±0.14^bc
H-Que组	1.13±0.12^bcd	0.45±0.05^bcd	0.74±0.08^bcd
H-Que+MIP-1α组	2.05±0.21^e	1.83±0.18^e	2.43±0.23^e
F	69.661^＊＊	72.296^＊＊	128.587^＊＊

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