Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses
Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses
复制标题
DOI：
10.1007/s12035-014-9012-2
复制
发表时间：
2016-04-01
影响因子：
5.1
通讯作者：
Cho, Ik-Hyun
中科院分区：
文献类型：
--
作者：
Lee, Min Jung;Jang, Minhee;Cho, Ik-Hyun
蜂毒针刺(BVA)对神经退行性疾病的防治机制尚不清楚。我们研究了在胫骨前缘外侧的足三里穴给予BVA(0.25和0.8 mg/kg)是否对髓鞘碱性蛋白(MBP)(68-82)诱导的急性实验性自身免疫性脑脊髓炎(EAE)大鼠有有利影响。在急性EAE大鼠的临床体征(神经功能障碍和体重减轻)方面，BVA预处理(从免疫前1h起每隔3天一次)比BVA治疗后(每天免疫后1次)更有效。正常大鼠经ST36穴位注射BVA后，未出现临床体征。BVA可抑制急性EAE大鼠脊髓脱髓鞘、胶质细胞活化、细胞因子[干扰素-γ、IL-17、IL-17A、肿瘤坏死因子-α、IL-1β]、趋化因子[RANTES、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1α]、诱导型一氧化氮合酶(INOS)的表达，以及p38丝裂原活化蛋白激酶(MAPK)和核因子-kappaB(p65和磷酸化-I kappa Bα)信号通路的激活。BVA可降低急性EAE大鼠脊髓和淋巴结中的CD4(+)、CD4(+)/干扰素-γ(+)和CD4(+)/IL-17(+)T细胞的数量，而增加CD4(+)/Foxp3(+)T细胞的数量。BVA在6个安慰剂穴位(SP9、GB39和4个非穴位)对急性EAE大鼠的治疗没有积极的效果。有趣的是，与在6个安慰剂穴位使用BVA相比，在ST36穴位开始和治疗后，BVA显著减轻了髓鞘少突胶质细胞糖蛋白(MOG)(35-55)诱导的慢性EAE小鼠的神经损伤。我们的研究结果有力地表明，BVA配合ST36穴位治疗可以通过上调调节性T细胞和抑制T辅助细胞(Th)17和Th1反应来延缓或减弱EAE的发展和进展。这些结果值得进一步研究BVA作为治疗中枢神经系统自身免疫性疾病的方法。
The protective and therapeutic mechanism of bee venom acupuncture (BVA) in neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36) acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a myelin basic protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of body weight) of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial activation, expression of cytokines [interferon (IFN)-gamma, IL-17, IL-17A, tumor necrosis factor-alpha (TNF-alpha), and IL-1 beta], chemokines [RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1 alpha], and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B (p65 and phospho-I kappa B alpha) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-gamma(+), and CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36 acupoint markedly attenuated neurological impairment in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo acupoints. Our findings strongly suggest that treatment with BVA with ST36 acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and suppressing T-helper (Th) 17 and Th1 responses. These results warrant further investigation of BVA as a treatment for autoimmune disorders of the central nervous system.