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灵芝多糖肽(GLPP)通过抑制 NF-κB 和 MAPK 信号通路来减轻大鼠的风湿性关节炎。

Ganoderma lucidum polysaccharide peptide (GLPP) attenuates rheumatic arthritis in rats through inactivating NF-κB and MAPK signaling pathways.

机构信息

Department of Orthopaedics, the First Affiliated Hospital, Dalian Medical University, Dalian, China.

National Engineering Research Center of JUNCAO Technology, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

出版信息

Phytomedicine. 2023 Oct;119:155010. doi: 10.1016/j.phymed.2023.155010. Epub 2023 Aug 2.

DOI:10.1016/j.phymed.2023.155010
PMID:37586160
Abstract

BACKGROUND

Not many drugs with fewer side effects are available for the treatment of rheumatoid arthritis (RA). Ganoderma lucidum polysaccharide peptide (GLPP) has good immunomodulatory effects, but whether it is effective in managing RA is not clear.

PURPOSE

This study was conducted to examine the anti-RA activity and possible mechanisms of GLPP in collagen-induced arthritis (CIA) rats.

METHODS

Male Wistar rats were intradermally injected with bovine type II collagen in the tail base to establish the CIA model and were orally administered 100 or 200 mg/kg GLPP for 35 days. Paw thickness, clinical arthritis scores, gait analysis, organ index determination, blood cell counts, micro-CT imaging and pathological staining were performed on the rats. Liver and kidney function were measured by commercial kits, and antibody levels were measured by ELISA kits. RA-related protein levels were detected by Western blotting.

RESULTS

GLPP effectively alleviated CIA symptoms and reduced immune organ indexes, antibody levels and systemic organ injury. GLPP decreased the protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)2, MMP9, MMP13, BCL-2, OPN, β-Catenin, and hypoxia inducible factor (HIF)-1α and increased the protein expression of BAX in the joint tissues of CIA rats. Moreover, GLPP decreased the phosphorylation levels of p65, IκB-α and ERK1/2.

CONCLUSION

GLPP effectively alleviated RA symptoms in CIA rats by inhibiting the NF-κB and MAPK pathways. This study suggests a promising therapeutic effect of mushroom-derived polysaccharide peptides on RA.

摘要

背景

类风湿性关节炎(RA)的治疗药物副作用小的并不多。灵芝多糖肽(GLPP)具有良好的免疫调节作用,但它在治疗 RA 方面是否有效尚不清楚。

目的

本研究旨在探讨 GLPP 对胶原诱导性关节炎(CIA)大鼠的抗 RA 活性及可能机制。

方法

雄性 Wistar 大鼠尾根部皮内注射牛 II 型胶原建立 CIA 模型,连续灌胃给予 GLPP 100 或 200mg/kg 35 天。检测大鼠爪厚度、临床关节炎评分、步态分析、脏器指数测定、血细胞计数、Micro-CT 成像和病理染色。采用商业试剂盒测定肝肾功能,ELISA 试剂盒测定抗体水平。Western blot 法检测 RA 相关蛋白水平。

结果

GLPP 能有效缓解 CIA 症状,降低免疫器官指数、抗体水平及全身脏器损伤。GLPP 降低了 CIA 大鼠关节组织中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、基质金属蛋白酶(MMP)2、MMP9、MMP13、骨桥蛋白(OPN)、BCL-2、β-连环蛋白(β-Catenin)和缺氧诱导因子(HIF)-1α的蛋白表达,增加了 Bax 的蛋白表达。此外,GLPP 降低了 p65、IκB-α 和 ERK1/2 的磷酸化水平。

结论

GLPP 通过抑制 NF-κB 和 MAPK 通路有效缓解 CIA 大鼠的 RA 症状。本研究提示蘑菇来源的多糖肽对 RA 具有潜在的治疗作用。

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