目的 探討蜂毒肽對(duì)膠原誘導(dǎo)關(guān)節(jié)炎大鼠模型免疫調(diào)節(jié)的影響。方法 成功建立膠原誘導(dǎo)關(guān)節(jié)炎大鼠模型，隨機(jī)分為模型組、蜂毒肽（0.5 mg/kg）組、甲氨蝶呤（1 mg/只）組，每組6只，另選取未造模大鼠為對(duì)照組；造模第14天起，隔日1次ip蜂毒肽，每周1次ip甲氨蝶呤，對(duì)照組、模型組ip等量生理鹽水，給藥21 d。觀察關(guān)節(jié)腫脹程度、進(jìn)行關(guān)節(jié)炎指數(shù)（AI）評(píng)分；給藥結(jié)束后，收集血清，ELISA法檢測(cè)血清中免疫球蛋白G （IgG）、IgG1、IgG2a、干擾素-γ（IFN-γ）、白細(xì)胞介素-4（IL-4）水平；分離大鼠脾臟，提取淋巴細(xì)胞，流式細(xì)胞術(shù)檢測(cè)Th1、Th2細(xì)胞比例。結(jié)果 蜂毒肽組大鼠關(guān)節(jié)皮膚發(fā)紅，關(guān)節(jié)腫脹明顯減輕；與模型組比較，蜂毒肽顯著抑制AI評(píng)分（P<0.05）；顯著降低血清中IgG、IgG2a、IFN-γ濃度（P<0.05），升高IgG1、IL-4濃度（P<0.05）；顯著下調(diào)Th1細(xì)胞比例、Th1/Th2比值（P<0.05），上調(diào)Th2細(xì)胞比例（P<0.05）。結(jié)論 蜂毒肽能通過調(diào)節(jié)Th1/Th2平衡抑制膠原誘導(dǎo)關(guān)節(jié)炎大鼠的炎癥。

Objective To investigate the effect of melittin on the immune regulation of arthritis rat model induced by collagen.Methods The arthritis rat model was successfully established and randomly divided into model group,melittin group and methotrexate group with six rats in each group.In addition,rats without modeling were selected as control group.After 14 d,the melittin were ip injected once every other day and methotrexate were ip given once a week for 21 d.The model group was given the same amount of normal saline,and the degree of joint swelling was observed and calculated.After drug administration,the serum was collected from rats,and the serum levels of IgG,IgG1,IgG2a,IFN-γ,and IL-4 were detected by ELISA.The spleen was isolated from rats and lymphocytes were extracted.The proportion of Th1 and Th2 cells was detected by flow cytometry.Results In the melittin group,there was redness in the joint skin,and the swelling of the joint was obviously alleviated.Compared with model group,melittin significantly inhibited joint swelling score (P< 0.05),reduced the concentrations of IgG,IgG2a,and IFN-γ in serum (P< 0.05),increased concentrations of IgG1 and IL-4(P< 0.05),down-regulated the ratio of Th1 cells and the ratio of Th1/Th2(P< 0.05),and up-regulated the ratio of Th2 cells (P< 0.05).Conclusion Melittin can inhibit the inflammation in the collageninduced arthritis by regulating Th1/Th2 balance.

國家自然科學(xué)基金（81271950）；深圳市科技計(jì)劃基礎(chǔ)研究項(xiàng)目（JCYJ20170307162827158、JCYJ20160429183052202）；深圳市衛(wèi)生計(jì)生科研項(xiàng)目（201506091、201606050）；深圳市南山區(qū)科技項(xiàng)目（2015021、2015043、2015047、2017016）