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姜黄素通过 HMGB1/TLR4/NF-ΚB 通路在心理应激大鼠咬肌中发挥局部抗炎和抗氧化作用。

Curcumin plays a local anti-inflammatory and antioxidant role via the HMGB1/TLR4/NF-ΚB pathway in rat masseter muscle under psychological stress.

机构信息

State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Air Force Medical University, Xi'an, China.

Department of Stomatology, Seventh Medical Center of Chinese, PLA General Hospital, Beijing, China.

出版信息

J Oral Rehabil. 2022 Feb;49(2):249-257. doi: 10.1111/joor.13289. Epub 2021 Dec 13.

DOI:10.1111/joor.13289
PMID:34865233
Abstract

BACKGROUND AND OBJECTIVE

Psychological stress causes structural and metabolic dysfunction of masseter muscles. The anti-inflammatory and anti-oxidative polyphenol curcumin plays a local antioxidant role in rat masseter muscles under psychological stress by an as-yet-unknown mechanism. The present study aimed to assess curcumin anti-inflammatory and anti-oxidative effects on masseter muscle and its possible molecular mechanisms.

METHODS

We constructed a rat model of chronic unpredictable moderate stress (CUMS). Psychological stress was assessed by determining the levels of adrenocorticotropic hormone (ACTH) and cortisol in serum. Enzyme-linked immunosorbent assays measured inflammatory cytokines and markers of oxidative stress in masseter muscles. Levels of high-mobility group box 1 (HMGB1), interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were determined using quantitative PCR analyses and immunofluorescent staining. Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) activation were examined using western blotting.

RESULTS

The CUMS group showed increased serum cortisol and ACTH levels. Pathological changes in the ultrastructure, oxidative stress and inflammatory cytokines in the masseter muscles were also observed. Curcumin treatment (50, 100 mg/kg) ameliorated these changes significantly by varying degrees. Mechanistically, increased levels of phosphorylated NF-κB, toll-like receptor 4 and HMGB1 were observed, which were also ameliorated by curcumin treatment.

CONCLUSION

Curcumin can reduce local pathological changes, levels of oxidative stress and inflammatory factors in masseter muscles. Psychological stress activates HMGB1 expression and increases the expression of downstream TLR4 and p-NF-κB, which could be reduced by curcumin. Thus, curcumin might exert anti-inflammatory and antioxidant effects in masseter muscles via the HMGB1/TLR4/NF-κB pathway.

摘要

背景与目的

心理应激会导致咬肌的结构和代谢功能障碍。姜黄素是一种具有抗炎和抗氧化作用的多酚,其通过一种未知的机制在心理应激下对大鼠咬肌发挥局部抗氧化作用。本研究旨在评估姜黄素对咬肌的抗炎和抗氧化作用及其可能的分子机制。

方法

我们构建了慢性不可预测轻度应激(CUMS)大鼠模型。通过测定血清中促肾上腺皮质激素(ACTH)和皮质醇的水平来评估心理应激。酶联免疫吸附试验测定咬肌中炎症细胞因子和氧化应激标志物。采用定量 PCR 分析和免疫荧光染色测定高迁移率族蛋白 1(HMGB1)、白细胞介素(IL)-1β、IL-6 和肿瘤坏死因子-α(TNF-α)的水平。采用 Western blot 检测 Toll 样受体 4(TLR4)和核因子 kappa B(NF-κB)的激活。

结果

CUMS 组血清皮质醇和 ACTH 水平升高。咬肌的超微结构、氧化应激和炎症细胞因子也发生了病理变化。姜黄素(50、100mg/kg)治疗可不同程度地改善这些变化。机制上,观察到磷酸化 NF-κB、Toll 样受体 4 和 HMGB1 水平升高,姜黄素治疗也改善了这些变化。

结论

姜黄素可减轻咬肌局部病理变化、氧化应激和炎症因子水平。心理应激激活 HMGB1 表达,并增加下游 TLR4 和 p-NF-κB 的表达,姜黄素可减少这些变化。因此,姜黄素可能通过 HMGB1/TLR4/NF-κB 途径发挥对咬肌的抗炎和抗氧化作用。

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