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艾灸通过白细胞介素-4/信号转导子和转录激活子6通路调节类风湿关节炎中巨噬细胞的极化。

Moxibustion regulates the polarization of macrophages through the IL-4/STAT6 pathway in rheumatoid arthritis.

作者信息

Zhong Yu-Mei, Zhang Lin-Lin, Lu Wen-Ting, Shang Ya-Nan, Zhou Hai-Yan

机构信息

Chengdu Integrated TCM & Western Medicine Hospital/Chengdu First People's Hospital, Chengdu 610041, China; Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

出版信息

Cytokine. 2022 Apr;152:155835. doi: 10.1016/j.cyto.2022.155835. Epub 2022 Feb 28.

DOI:10.1016/j.cyto.2022.155835
PMID:35240467
Abstract

OBJECTIVE

To observe the effects of moxibustion on "Shenshu" and "Zusanli" on macrophage polarization and IL-4/STAT6 signaling pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA.

METHODS

The rats' right hind paws were injected with freund's complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The researchers measured the thickness of the foot pad. ELISA and Histological Analysis were performed to observe the anti-inflammatory effect of moxibustion. Then researchers detected the expression of macrophage phenotype and the expression of IL-4/STAT6 signaling pathway related molecules.

RESULTS

It was observed that after the injection of FCA, the rats' feet showed obvious symptoms of redness and swelling. But the symptoms were significantly improved when moxibustion was employed. The study found lower IL-23 and higher IL-4 level in the serum of FCA-injected rats after moxibustion treatment. HE staining showed that the synovium of the RA group was hyperemia and edema, with a large number of inflammatory cells infiltration and vascular dilatation. In the moxibustion group, the degree of synovial hyperemia and edema was improved, and the infiltration of inflammatory cells and vascular dilation were reduced. The study also found that there wer differences among the expressions of macrophage phenotypes in RA, and this was shown by the high expression of CD86 and low expression of CD206. However, the polarization of macrophages in the moxibustion group changed, and that was manifested by enhanced M2-polarized Mφs and inhibited M1-polarized Mφs. Meanwhile, moxibustion suppressed the activation of JAK1, JAK3 and STAT6 in the IL-4/STAT6 signaling pathway, which contributed to the polarization of M2 .

CONCLUSION

The results demonstrate that moxibustion not only suppresses the polarization of M1, but also promotes the polarization of M1. The anti-inflammatory effect of moxibustion may be related to the regulation of macrophage polarization through IL-4/STAT6 signaling pathway.

摘要

目的

观察艾灸“肾俞”和“足三里”对类风湿关节炎(RA)大鼠巨噬细胞极化及IL-4/STAT6信号通路的影响。进一步探讨艾灸治疗RA可能的抗炎机制。

方法

将弗氏完全佐剂(FCA)注射到大鼠右后足建立RA模型。注射FCA 7天后,对肾俞(BL23)和足三里(ST36)穴位进行艾灸治疗,每日1次,共3周。研究人员测量足垫厚度。采用ELISA和组织学分析观察艾灸的抗炎作用。然后检测巨噬细胞表型的表达及IL-4/STAT6信号通路相关分子的表达。

结果

观察到注射FCA后,大鼠足部出现明显的红肿症状。但采用艾灸后症状明显改善。研究发现艾灸治疗后,注射FCA大鼠血清中IL-23水平降低,IL-4水平升高。HE染色显示,RA组滑膜充血水肿,有大量炎性细胞浸润和血管扩张。艾灸组滑膜充血水肿程度改善,炎性细胞浸润和血管扩张减少。研究还发现RA中巨噬细胞表型表达存在差异,表现为CD86高表达和CD206低表达。然而,艾灸组巨噬细胞极化发生改变,表现为M2极化的巨噬细胞增强,M1极化的巨噬细胞受到抑制。同时,艾灸抑制了IL-4/STAT6信号通路中JAK1、JAK3和STAT6的激活,这有助于M2极化。

结论

结果表明,艾灸不仅抑制M1极化,还促进M2极化。艾灸的抗炎作用可能与通过IL-4/STAT6信号通路调节巨噬细胞极化有关。

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