针刺治疗Cx43基因敲除鼠胶原性关节炎的免疫学研究(英文)

IMMUNOLOGICAL STUDY ON ACUPUNCTURE TREATMENT OF COLLAGEN-INDUCED ARTHRITIS IN CX43-KNOCK-OUT RATS

目的:探讨针刺治疗Cx43基因敲除鼠胶原性关节炎(Ⅱcollagen-induced arthritis,CIA)的疗效及免疫学机制。方法:以Cx43基因敲除杂合型(Cx43^(+/-))和野生型(Cx43^(+/+))小鼠为研究对象,用牛Ⅱ型胶原诱导成CIA模型。在初次免疫后第4周开始针刺治疗,连续3周。观察关节炎分数,流式细胞术检测脾淋巴细胞中Th细胞亚群含量。结果:Cx43^(+/-)小鼠CIA发病率及关节炎分数明显低于Cx43^(+/+)小鼠;针刺抑制Cx43^(+/+)CIA小鼠Th1细胞分泌,降低Th1/Th2比值,对Th2细胞的分泌无明显影响;而针刺对Cx43^(+/-)CIA小鼠Th细胞亚群含量无明显影响。结论:针刺对Cx43^(+/+)CIA小鼠疗效明显优于Cx43^(+/-) CIA小鼠,提示针刺疗效与Cx43基因相关,其疗效可能是通过调节Th1/Th2使之接近动态平衡而起作用的,针刺疗效与这种调节作用成正相关。

Objective To observe the therapeutic effect of acupuncture for collagen-induced arthritis （CIA） in Cx43 knock-out mice and its underlying immunological mechanism.Methods Heterozygote （Cx43^＋/-） mice （n=64） and wild-type （Cx43^＋/＋） mice （n=46） were used in the present study.CIA model was es- tablished by intracutaneous injection of bovine collagenⅡ（immunonization）.Acupuncture of Zúsānlǐ（足三里ST36） was carried out from the 4^th week on after the initial immunization,once a day for 3 weeks.Arthritis score and days of onset of CIA were recorded.Intracellular contents of Th subgroups of splenic lymphocytes were detected with flow cytometry.Results The incidence rate of CIA and arthritis score in Cx43^＋/- mice were significantly lower than those in Cx43^＋/＋ mice （P〈0.05）.In Cx43^＋/＋ mice,3 weeks after acupuncture treatment,the score of arthritis symptoms and signs in acupuncture group was significantly lower than that in model group （P〈0.01）,while in Cx43^＋/- mice,no significant difference was found between model group and acupuncture group in arthritis score （P〉0.05）.In comparison with control group,percentages of both Thl and Th2 and Th1/Th2 increased significantly in 0x43^＋/＋ CIA model group （P〈0.05）,while compared with model group,the percentage of Th1,Th2 and Th1/Th2 in acupuncture group decreased evidently （P〈0.05） or moderately,showing that acupuncture can effectively suppress arthritis-induced increase of Thl in Cx43^＋/＋ mice.In 0x43^＋/- mice,Th1 level and Th1/Th2 of CIA model group increased considerably in comparison with control group （P〈0.05）,while compared with model group,the Th1,Th2 and Th1/Th2 of acupuncture group had no significant changes （P〉0.05）,indicating that the effect of acupuncture in suppressing increase of Th1 percent and Th1/Th2 was eliminated.Conclusion Acupuncture of Zúsānlǐ（足三里ST 36） can effectively relieve CIA symptoms and signs and inhibit increase of splenic Th1 in Cx43^＋/＋ mice but has no any effect on CIA score,Th1,Th2 and Th1/Th2 in Cx43^＋/- mice.It shows the effect of acupuncture in improving CIA is closely related to Cx43 gene.