Effect of electroacupuncture on JAK2/STAT3 pathway in synovial tissues of rats with rheumatoid arthritis
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To observe the effect of electroacupuncture (EA) on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in knee joint synovial tissues of rats with rheumatoid arthritis (RA) and to explore the action mechanism of EA on RA.
Twelve of the 48 SPF male Sprague-Dawley (SD) rats were assigned to a normal group by the random number table method. The remaining 36 rats were subjected to RA model preparation by intradermal injection of the Freund’s complete adjuvant into the right hind foot pad of each rat under sterile conditions. After the model was successfully prepared, rats were then divided into a model group, a drug group and an EA group according to a random number table method (n=12). Rats in the drug group were treated with 2 mL aqueous solution of tripterygium glycosides [8.1 mg/(kg·bw)]; rats in the EA group were treated with EA at bilateral Yanglingquan (GB 34) and Zusanli (ST 36), for 30 min each time; rats in the normal group and the model group were placed in a special rat fixation tank for 30 min each time, and received the same dose of normal saline as those in the drug group. Rats in all groups received intervention once a day for 4 weeks. Diameter of rat ankle joint and rat arthritis index were measured before and after the intervention. At the end of the experiment, the expressions of phospho-JAK2 and phospho-STAT3 were determined by immunohistochemistry. Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect JAK2 and STAT3 mRNAs expressions.
After the model was produced, the arthritis index <2 was considered successful in model preparation. Compared with the model group, the ankle joint diameters and arthritis indexes of rats in the drug group and the EA group were significantly lower (all P>0.01); immunohistochemical staining cells with phospho-JAK2 and phospho-STAT3 were significantly decreased (all P>0.01); the expression levels of JAK2 and STAT3 mRNAs were decreased with statistical differences (all P>0.01). There were no significant differences between the EA group and the drug group (all P<0.05).
EA can alleviate the inflammatory response of RA rats, improve their pathological conditions, reduce the expressions of phospho-JAK2 and phospho-STAT3 in the synovial tissue of knee joint, and decrease the expressions of JAK2 and STAT3 mRNAs. The therapeutic effect of EA is comparable to that of the tripterygium glycosides. The mechanism of EA treatment may be related to the inactivation of the JAK2/STAT3 pathway.
KeywordsAcupuncture Therapy Electroacupuncture Point, Yanglingquan (GB 34) Point, Zusanli (ST 36) Arthritis, Rheumatoid Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT 3) Pathway Rats
采用随机数字表法从48只SPF级雄性SD大鼠中取12只为正常组, 其余36只大鼠无菌条件下右后足跖皮内注射弗氏完全佐剂复制RA模型, 造模成功后再按照数字表随机分为模型组、药物组和电针组, 每组12只。 药物组大鼠接受2 m L雷公藤多苷片水溶液灌胃[8.1 mg/(kg·bw)]; 电针组大鼠接受电针双侧阳陵泉和足三里治疗, 电针刺激每次持续30 min。 正常组和模型组大鼠被置于特制大鼠固定筒中, 每次持续30 min, 并接受与药物组同等剂量的生理盐水灌胃。 每组大鼠每天干预1次, 连续干预4周。 在干预前后检测大鼠踝关节直径数值和大鼠关节炎指数。 实验结束后免疫组化法观察磷酸化JAK2(phospho-JAK2)和磷酸化STAT3(phospho-STAT3)的表达, 实时荧光定量聚合酶链反应(RT-qPCR)法检测JAK2和STAT3 mRNA表达。
模型复制后, 关节炎指数大于2视为模型制备成功。 与模型组比较, 药物组和电针组大鼠踝关节直径数值和关节炎指数明显降低, 组间具有统计学差异(均P<0.01); phospho-JAK2及phospho-STAT3免疫组化阳性染色细胞减少, 组间具有统计学差异(均P<0.01); JAK2和STAT3 mRNA表达量下降, 组间具有统计学差异(均P<0.01)。 电针组与药物组比较, 均无统计学差异(均P>0.05)。
电针可以减轻 RA 大鼠的炎性反应, 改善其病理状况, 减少膝关节滑膜组织 phospho-JAK2 和 phospho-STAT3 的表达, 降低 JAK2 及 STAT3 mRNA 表达量, 其治疗作用与雷公藤多苷片相当, 电针治疗作用机制可能与抑制 JAK2/STAT3 通路激活有关。
【关键词】针刺疗法 电针 穴, 阳陵泉 穴, 足三里 关节炎 类风湿 Janus 激酶 2/STAT3 通路 大鼠
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This work was supported by Research Fund Project for Introduced Talents of Yijishan Hospital (弋矶山医院引进人才科研基金项目, No. YR201809).
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