电针对慢性炎性疼痛大鼠Wnt/β-catenin以及ERK/MAPK信号通路相关蛋白表达的影响  

Effects of Electroacupuncture on the Expression of Wnt/β-Catenin and ERK/MAPK Signaling Pathway in Chronic Inflammatory Pain Rats

作　　者：桑亚男[1] 郭现辉[1] 董升[1] 王权亮[2] 张安东[1] 闫瑞 Sang Yanan;Guo Xianhui;Dong Sheng;Wang Quanliang;Zhang Andong;Yan Rui(The Third Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Affiliated Hospital of Henan Academy of Traditional Chinese Medicine,Zhengzhou 450000,China;Fuwai Hua Central Vascular Disease Hospital,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学第三附属医院,郑州450000 [2]河南省中医药研究院附属医院,郑州450000 [3]阜外华中心血管病医院,郑州450000

出　　处：《世界科学技术-中医药现代化》2022年第11期4427-4434,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：河南省中医管理局普通课题(2019ZY2102):功能训练结合医用臭氧水穴位及关节腔注射治疗膝骨关节炎的疗效评价及机理研究,负责人:王权亮。

摘　　要：目的 探究电针(EA)对慢性炎性疼痛大鼠Wnt/β-catenin信号通路和ERK/MAPK信号通路的调控作用。方法 通过完全弗氏佐剂建立慢性炎性疼痛大鼠(CFA)模型。实验分为4组:对照组(NS组)、模型组(CFA组)、模型组+电针组(CFA+EA组)和模型组+假电针组(CFA+Sham EA组),每组6只大鼠。模型建立8天后进行EA治疗,每天1次,每次30 min。用Up-down法评价机械痛阈值,用丙酮刺激大鼠致炎足底观察冷刺激诱发痛的反应评分,用ELISA检测血清和左后足组织中前列腺素E2(Urinary prostaglandin E2,PGE2)、白介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白介素-1β(Interleukin-1β,IL-1β)和脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)的表达水平,用Western blot检测左后足组织中Wnt家族成员1蛋白(Wnt family member 1,Wnt-1)、β连环蛋白(catenin beta1,β-catenin)和糖原合酶激酶-3(Glycogen synthase kinase-3 beta,GSK-3β)的表达水平以及cAMP反应元件结合蛋白(cAMP response element binding protein,CREB)和细胞外信号调节激酶(Extracellular signal-regulated kinase,ERK)蛋白的磷酸化水平。结果 与CFA模型组相比,治疗后第5天及第7天,EA显著提高了CFA大鼠的机械痛阈值(P<0.05),并显著降低了CFA大鼠的冷刺激评分(P<0.05)。此外,EA显著降低了CFA大鼠血清和左后足组织中PGE2、IL-6、TNF-α、IL-1β和BDNF的表达水平和左后足组织中Wnt-1和β-catenin的蛋白表达水平以及CREB和ERK蛋白的磷酸化水平(均P<0.05),并显著升高了左后足组织中GSK-3β的蛋白表达水平(P<0.05)。结论 EA显著改善了大鼠慢性炎性疼痛,其机制可能与抑制Wnt/β-catenin信号通路和ERK/MAPK信号通路有关。Objective To explore the effect of electroacupuncture(EA) on the expression of Wnt/β-catenin and ERK/MAPK signaling pathway in rats with chronic inflammatory pain. Methods The model of chronic inflammatory pain(CFA) rats was established by using complete Freund’s adjuvant. There were four groups in the experiment: control group(NS group), model group(CFA group), model+electroacupuncture group(CFA+EA group) and model +Sham electroacupuncture group(CFA+Sham EA group), with 6 rats in each group. After 8 days of CFA model establishment,the EA group was treated once a day for 30min each time. The mechanical pain threshold was evaluated by up-down method. The response score of cold-induced pain was observed by stimulating the inflammatory plantar of rats with acetone. The expression levels of PGE2, IL-6, TNF-α, IL-1β, and BDNF in serum and left hindfoot tissue were detected by ELISA, and the expression levels of Wnt-1, β-catenin and GSK-3 and the phosphorylation levels of CREB and ERK proteins in left hindfoot tissue were detected by Western blot. Results Compared with the CFA group, 5 days and 7 days after treatment, the EA significantly improved the CFA mechanical pain threshold of rats(P<0.05), and significantly reduced the cold stimulation(P<0.05). In addition, EA significantly reduced the expression levels of PGE2,IL-6, TNF-α, IL-1β, and BDNF in serum and left hindfoot tissue, and decreased the protein expression levels of Wnt-1 and β-catenin and the phosphorylation levels of CREB and ERK proteinsin in left hindfoot tissue of CFA rats(P<0.05),and significantly increased the protein expression levels of GSK-3β in left hindfoot tissue(P<0.05). Conclusion EA significantly improved chronic inflammatory pain in rats, and the mechanism may be related to inhibit the Wnt/β-catenin and ERK/MAPK signaling pathway.

关 键 词：电针 WNT/Β-CATENIN信号通路 ERK/MAPK信号通路 慢性炎症 疼痛 完全弗氏佐剂 

分 类 号：R285.5[医药卫生—中药学]