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艾灸干预通过下调佐剂性关节炎大鼠滑膜组织 NLRP3/Caspase-1/IL-1β 信号通路改善滑膜炎。

Moxibustion intervention improves synovitis by down-regulating NLRP3/Caspase-1/IL-1β signaling of synovial tissue in rats with adjuvant arthritis.

机构信息

Graduate School of Anhui University of Chinese Medicine, Hefei 230031, China.

The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230061.

出版信息

Zhen Ci Yan Jiu. 2023 Nov 25;48(11):1111-1116. doi: 10.13702/j.1000-0607.20220801.

Abstract

OBJECTIVES

To observe the effect of moxibustion on activities of NOD-like receptor family protein 3 (NLRP3)/cysteine aspartic acid specific protease-1 (Caspase-1)/interleukin-1β (IL-1β) signaling pathway in rats with adjuvant arthritis (AA), so as to explore its mechanisms underlying improvement of rheumatoid arthritis (RA). Me-thods Thirty male Wistar rats were randomly divided into normal control, AA model and moxibustion groups, with 10 rats in each group. The AA model was replicated by raising in wind, cold and damp environment combined with complete Freund's adjuvant injection. In the moxibustion group, moxibustion was applied to bilateral "Shenshu" (BL23) and "Zusanli"(ST36) for 20 min each time, once daily for 21 days. Changes of joint swelling degree (JSD) and arthritis index (AI) in each group were observed. The ultrastructural changes of synovial cells in each group were observed by transmission electron microscopy. The protein expression levels of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, tumor necrosis factor-α (TNF-α) and IL-1β in the synovial tissues of the knee joint were measured by Western blot.

RESULTS

Compared with the normal control group, JSD, AI and the protein expressions of NLRP3, ASC, Caspase-1, TNF-α and IL-1β in the synovial tissues were significantly increased (<0.01) in the model group. In comparison with the model group, JSD, AI and the protein expression levels of NLRP3, ASC, Caspase-1, TNF-α and IL-1β were significantly decreased (<0.01) in the moxibustion group. Results of transmission electron microscope showed an irregular and vague nuclear membrane of synovial cells, and unclear mitochondrial membrane boundary with sparse, swelling crests in the model group, which was relatively milder in the damage degree in the moxibustion group.

CONCLUSIONS

Moxibustion can relieve the inflammatory response in the synovial membrane of AA rats, which may be related to its function in down-regulating synovial NLRP3/Caspase-1/IL-1β inflammatory signaling.

摘要

目的

观察艾灸对佐剂性关节炎(AA)大鼠 NOD 样受体家族蛋白 3(NLRP3)/半胱天冬氨酸特异性蛋白酶-1(Caspase-1)/白细胞介素-1β(IL-1β)信号通路活性的影响,探讨艾灸治疗类风湿关节炎(RA)的作用机制。

方法

30 只雄性 Wistar 大鼠随机分为正常对照组、AA 模型组和艾灸组,每组 10 只。采用风冷、寒湿环境联合完全弗氏佐剂注射复制 AA 模型。艾灸组双侧“肾俞”(BL23)和“足三里”(ST36)艾灸 20 min,每日 1 次,共 21 天。观察各组大鼠关节肿胀度(JSD)和关节炎指数(AI)的变化,透射电镜观察各组大鼠滑膜细胞的超微结构变化,Western blot 法检测各组大鼠膝关节滑膜组织 NLRP3、凋亡相关斑点样蛋白(ASC)、Caspase-1、肿瘤坏死因子-α(TNF-α)和 IL-1β 蛋白表达水平。

结果

与正常对照组比较,模型组大鼠 JSD、AI 及滑膜组织 NLRP3、ASC、Caspase-1、TNF-α和 IL-1β 蛋白表达均明显升高(P<0.01);与模型组比较,艾灸组大鼠 JSD、AI 及滑膜组织 NLRP3、ASC、Caspase-1、TNF-α和 IL-1β 蛋白表达均明显降低(P<0.01)。透射电镜结果显示,模型组滑膜细胞核膜不规则、模糊,线粒体膜边界不清,嵴稀疏肿胀,艾灸组损伤程度相对较轻。

结论

艾灸能缓解 AA 大鼠滑膜炎症反应,其作用机制可能与下调滑膜 NLRP3/Caspase-1/IL-1β 炎症信号通路有关。

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