HPAA在艾灸调控类风湿性关节炎大鼠滑膜组织NF-kB信号通路中的作用Involvement of the Hypothalamus-pituitary-adrenal Axis in Moxibustion-induced Changes of NF-kB Signaling in the Synovial Tissue in Rheumatic Arthritis Rats
高骏;刘旭光;黄迪君;唐勇;周海燕;尹海燕;陈婷;
GAO Jun,LIU Xu-guang,HUANG Di-jun,TANG Yong,ZHOU Hai-yan,YIN Hai-yan,CHEN Ting (Department of Acu-moxibustion,Chengdu University of Chinese Medicine,Chengdu 610075,China)
摘要(Abstract):
目的:通过对下丘脑-垂体-肾上腺轴(HPAA)在艾灸调控类风湿性关节炎(RA)大鼠滑膜组织核转录因子(NF-kB)信号通路中的作用分析,深入挖掘艾灸治疗RA抗炎效应的细胞信号转导作用机制。方法:雄性SD大鼠50只,随机分为空白组、模型组、艾灸组、摘肾上腺组、假手术组,每组各10只。右后足足垫部皮内注入福氏完全佐剂0.1mL制作RA模型。造模成功后第6天手术摘除摘肾上腺组大鼠双侧肾上腺。造模第7天开始艾灸大鼠"肾俞""足三里"两穴各5壮,每日1次,治疗18d。观测计算大鼠足跖肿胀度,采用ELISA双抗夹心法检测大鼠血浆促肾上腺皮质激素(ACTH)和血清皮质醇(CS)含量,运用免疫组化法测定大鼠滑膜NF-kBp65活性。结果:造模后大鼠右后足容积,模型组、艾灸组、摘肾上腺组和假手术组显著大于空白组(P<0.01);艾灸后大鼠右后足容积,艾灸组、假手术组显著小于模型组(P<0.01),摘肾上腺组显著大于空白组、艾灸组(P<0.01,P<0.05)。大鼠夜间血浆ACTH水平,模型组显著低于空白组(P<0.05),艾灸组、假手术组显著高于模型组(P<0.05),摘肾上腺组显著低于空白组、模型组、艾灸组(P<0.01)。大鼠夜间血清CS水平、滑膜NF-kBp65活性,模型组显著高于空白组(P<0.01),艾灸组、假手术组显著低于模型组(P<0.01),摘肾上腺组CS水平显著低于空白组、模型组、艾灸组(P<0.05),而滑膜NF-kBp65活性显著高于空白组、艾灸组(P<0.01)。结论:艾灸治疗实验性RA大鼠具有确切的抗炎效应,其抗炎效应的发挥需依赖于HPAA的完整。艾灸可能通过调节HPAA功能,从而抑制NF-kB炎性信号通路而发挥抗炎作用。
Objective To observe the effect of moxibustion of "Shenshu" (BL 23) and "Zusanli" (ST 36) on synovial nuclear factor (NF)-kB p 65 expression,and plasma adrenocorticotropic hormone (ACTH) and serum cortisol (CS) contents in rheumatic arthritis (RA) rats with adrenalectomy (ADX) so as to study the underlying mechanism in ameliorating RA. Methods Fifty male SD rats were randomly divided into control (n=10),model (n=10),moxibustion (n=10),ADX (n=10) and false ADX (n=10) groups according to SPSS-aided random digits table. RA model was established by injecting 0.1 mL Freund's complete adjuvant into the right paw. ADX operation was performed on the sixth day after successful establishment of RA model. Moxibustion was given to "Shenshu" (BL 23) and "Zusanli" (ST 36) from the 7th day on,five moxa cones each session,and once daily for 18 days. Then plasma ACTH and serum CS contents,for which the blood was collected during night,were detected by ELISA,and NF-kB p 65 immunoactivity in synovial tissue was detected by immunohistochemistry. Results In comparison with control group,the foot volumes (swelling degree) of model,moxibustion,ADX,and false ADX groups increased significantly (P<0.01),while compared with model group,the swelling degrees of moxibustion and false ADX groups were decreased remarkably after the treatment (P<0.01). No significant difference was found between ADX and model groups in the foot volume (P>0.05). Compared with control group,plasma ACTH content in RA model group decreased obviously (P<0.05),while serum CS level and NF-kB p 65 immunoactivity increased apparently in model group (P<0.01). Compared with model group,serum CS contents in moxibustion,ADX and false ADX groups and synovial NF-kB p 65 immunoactivity in moxibustion and false ADX groups reduced considerably (P<0.01,P<0.05). No significant difference was found between ADX and model groups in synovial NF-kB p 65 immunoactivity (P>0.05). Conclusion Moxibustion treatment can reduce inflammation reactions in RA rats,which is closely associated with its effects in upregulating plasma ACTH,downregulaing serum CS level and synovial NF-kB p 65 immunoactivity,and the intact hypothalamus-pituitary-adrenal axis (HPAA).
关键词(KeyWords):
艾灸;类风湿性关节炎;HPAA;滑膜NF-kBp65
Moxibustion; Rheumatoid arthritis; HPAA; Synovial NF-kB p 65
基金项目(Foundation): 国家自然科学基金(No.30672722);; 教育部新世纪优秀人才计划资助
作者(Authors):
高骏;刘旭光;黄迪君;唐勇;周海燕;尹海燕;陈婷;
GAO Jun,LIU Xu-guang,HUANG Di-jun,TANG Yong,ZHOU Hai-yan,YIN Hai-yan,CHEN Ting (Department of Acu-moxibustion,Chengdu University of Chinese Medicine,Chengdu 610075,China)
DOI: 10.13702/j.1000-0607.2010.03.007
参考文献(References):
- [1]杨馨,李继书,杨慎峭,等.艾灸对实验性类风湿性关节炎家兔滑膜细胞JAK-STAT信号通路影响的研究[J].针刺研究,2007,32(2):75-82.Yang X,Li J S,Yang S Q,et al.In-fluence of moxibustion on JAK-STAT signal transduction pathways of syno-vial cells in rheumatoid arthritis rab-bits[J].Zhen Ci Yan Jiu(Acupunct Res,Chin),2007,32(2):75-82.
- [2]刘旭光,黄迪君,郝亮,等.艾灸对类风湿性关节炎大鼠下丘脑-垂体-肾上腺皮质轴的影响[J].中国中医基础医学杂志,2003,9(2):57-59.Liu X G,Huang D J,Hao L,et al.Effect of the moxibustion on hypotha-lamic-pituitary-adrenal cortex axis in the rheumatoid arthritis rats[J].Zhongguo Zhong Yi Ji Chu Yi Xue Za Zhi(Chin J Basic Med Trad Chin Med,Chin),2003,9(2):57-59.
- [3]侯春风,梁宏达,王吉波.核转录因子kB和类风湿关节炎[J].中国组织工程研究与临床康复,2008,12(7):1304-1308.Hou C F,Liang H D,Wang J B.Nuclear transcription factor kappa B and rheumatoid arthritis[J].Zhong-guo Zu Zhi Gong Cheng Yan Jiu Yu Lin Chuang Kang Fu(J Clin Rehabil Tissue Engin Res,Chin),2008,12(7):1304-1308.
- [4]姚茹冰.核因子-kB与类风湿关节炎相关性的研究进展[J].医学研究生学报,2006,19(3):5-7.Yao R B.Research progress of the correlation between nuclear factor-kappa B and rheumatoid arthritis[J].Yi Xue Yan Jiu Sheng Xue Bao(J MedPostgraduates,Chin),2006,19(3):5-7.
- [5]林振和.核因子-kB信号转导途径的调节研究进展[J].国外医学.免疫学分册,2004,27(4):234-238.Lin Z H.Progress of research on the signal pathway of nuclear factor-kappa B[J].Guo Wai Yi Xue.Mian Yi Xue Fen Ce(Foreign Med Sci.Section I mmunol,Chin),2004,27(4):234-238.
- [6]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,1993:357.Cheng Q.Pharmacological Methodology of Chinese Drugs[M](Chin).Beijing:People’s Medical Publishing House,1993:357.
- [7]Harkness A L,Richter MB,Panayi G S,et al.Circadian vari-ationin disease activity in rheumatoid arthritis[J].Br Med J,1982,284(20):551-554.
- [8]Jorgensen C,Bressot N,Bologna C,et al.Dysregulation of the hypothalamus-pituitary axis in rheumatoid arthritis[J].J Rheumatol,1995,22(10):1829-1833.
- [9]孙丽丽,王志文,赵文毅.类风湿关节炎与下丘脑-垂体-肾上腺轴关系的研究概况[J].中国医药导报,2007,4(15):11-12.Sun L L,Wang Z W,Zhao W Y.Progress of research on the correlation between rheumatoid arthritis and hypothalamus-pi-tuitary-adrenal axis[J].Zhongguo Yi Yao Dao Bao(Chin Med Herald,Chin),2007,4(15):11-12.
- [10]李梢.类风湿性关节炎从络辨治及寒热方剂作用机理研究[D].北京:北京中医药大学,2001.Li S.Studies on the treat ment of rheumatoid arthritis based on collateral theory differentiation and on the underlying mechanismof the curative effects of the cold-and heat-Chinesemedical formula[D](Chin).Beijing:Beijing University of TCM,2001.
- [11]李晶,吴忠,张梅棣,等.类风湿关节炎患者白细胞介素-6与皮质醇节律的研究[J].中华风湿病学杂志,2002,6(4):252-254.Li J,Wu Z,Zhang M D,et al.Circadian variation of interleu-kin-6and cortisol in rheumatoid arthritis[J].Zhonghua Feng Shi Bing Xue Za Zhi(Chin J Rheumatol,Chin),2002,6(4):252-254.
- [12]何海艳,姚欣,黄茂.糖皮质激素抗炎作用的基因调控机制[J].国际呼吸杂志,2007,27(13):997-1000.He H Y,Yao X,Huang M.The Mechanism of gene regula-tion on glucocorticoids suppressing inflammation[J].Guo Ji Hu Xi Za Zhi(Int J Respir,Chin),2007,27(13):997-1000.
- [13]唐照亮,宋小鸽,章复清,等.艾灸治疗类风湿性关节炎抗炎免疫作用机理的研究[J].针刺研究,2003,28(4):292-298.Tang Z L,Song X G,Zhang F Q,et al.Study on the action mechanismof moxibustion in anti-inflammation and i mmuno-regulationin rheumatoid arthritis rats[J].Zhen Ci Yan Jiu(Acupunct Res,Chin),2003,28(4):292-298.
- [14]唐照亮,余新欣,陈全珠,等.6-羟多巴胺化学损毁小鼠外周交感神经对艾灸免疫调节作用的影响[J].针刺研究,2001,26(4):299-302.Tang Z L,Xu X X,Chen Q Z,et al.Effect of sympathectic nerve lesion on moxibustion induced i mmunoregulation in the mouse[J].Zhen Ci Yan Jiu(Acupunct Res,Chin),2001,26(4):299-302.
- 高骏
- 刘旭光
- 黄迪君
- 唐勇
- 周海燕
- 尹海燕
- 陈婷
GAO Jun- LIU Xu-guang
- HUANG Di-jun
- TANG Yong
- ZHOU Hai-yan
- YIN Hai-yan
- CHEN Ting (Department of Acu-moxibustion
- Chengdu University of Chinese Medicine
- Chengdu 610075
- China)
- 高骏
- 刘旭光
- 黄迪君
- 唐勇
- 周海燕
- 尹海燕
- 陈婷
GAO Jun- LIU Xu-guang
- HUANG Di-jun
- TANG Yong
- ZHOU Hai-yan
- YIN Hai-yan
- CHEN Ting (Department of Acu-moxibustion
- Chengdu University of Chinese Medicine
- Chengdu 610075
- China)