目的：探讨早期给予草分枝杆菌F.U.36注射液干预对哮喘小鼠CD4+CD25+调节性T细胞及TLR4表达的影响。方法：将雌性BALB/c小鼠30只随机分为正常对照组、哮喘组和哮喘草分枝杆菌F.U.36治疗组(哮喘/Utilin组)，每组10只。通过注射和雾化吸入鸡卵蛋白(OVA)制备哮喘模型。哮喘/Utilin组第一次致敏前2周腹腔注射草分枝杆菌F.U.36注射液0.57 μg，隔日一次，共3次。于末次激发后24 h处死。取小鼠左肺组织作病理切片观察炎症改变；同时利用流式细胞检测技术检测各组小鼠脾单个核细胞CD4+CD25+调节性T细胞占CD4+T细胞的百分率及CD4+CD25+调节性T细胞上的TLR4平均荧光强度。结果：哮喘小鼠脾单个核细胞CD4+CD25+ 调节性T细胞百分率明显降低(P0.05)；经草分枝杆菌F.U.36早期干预的哮喘小鼠脾单个核细胞CD4+CD25+调节性T细胞百分率和该细胞上表达的TLR4平均荧光强度较哮喘组均明显升高(P<0.01)。结论：早期应用草分枝杆菌F.U.36干预性治疗，可通过促进CD4+CD25+细胞上TLR4的表达和该细胞数目的增加以纠正哮喘小鼠机体的免疫紊乱而发挥其治疗作用。
Abstract
OBJECTIVE: To study the effects of early intervention on CD4+CD25+ regulatory T cells and TLR4 expression with Mycobacterium phlei F.U.36 in asthmatic mice. METHODS: Thirty female BALB/c mice were randomly divided into three groups: control, asthma model and Mycobacterium phlei F.U.36 treated asthma groups. Asthma was induced by sensitization and challenges with ovalbumin (OVA) in the later two groups. Mycobacterium phlei F.U.36 was intraperitoneally injected 2 weeks before the first sensitization (0.57 μg/time, once every other day for three times) in the intervention group. After 24 hrs of the last challenge, the mice were sacrificed and the left lung tissues were obtained for the observation of lung pathological changes. Splenic mononuclear cells were isolated. The percentage of CD4+CD25+ regulatory T cells in CD4+ T cells and the mean fluorescence intensity of TLR4 on CD4+ CD25+ T cells were detected by flow cytometry. RESULTS: The percentage of CD4+CD25+ regulatory T cells in the asthma model group was significantly lower than that in the control group (P<0.01), but the mean fluorescence intensity of TLR4 on CD4+CD25+ regulatory T cells was not significantly different from the control group. The percentage of CD4+CD25+ regulatory T cells and the mean fluorescence intensity of TLR4 on CD4+CD25+ regulatory T cells increased significantly in asthmatic mice receiving Mycobacterium phlei F.U.36 treatment compared with the asthma group (P<0.01). CONCLUSIONS: Early intervention with Mycobacterium phlei F.U.36 can increase TLR4 expression on CD4+CD25+ cells and the number of CD4+CD25+ regulatory T cells, and thus provides therapeutic effects in asthmatic mice.
关键词
哮喘 /
CD4+CD25+调节性T细胞 /
Toll样受体4 /
草分枝杆菌F.U.36 /
小鼠
Key words
Asthma /
CD4+CD25+ regulatory T cells /
Toll-like receptor 4 /
Mycobacterium phlei F.U.36 /
Mice
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参考文献
［1］Tournoy KG, Provoost S, Van Hove C, Joos G. The role of immune tolerance in asthma pathogenesis［J］. Curr Allergy Asthma Rep, 2006, 6(5): 437-443.
［2］Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide［J］. J Exp Med, 2003,197 (4): 403-411.
［3］沈华浩,王苹莉.支气管哮喘小鼠模型应用评价［J］.中华结核和呼吸杂志,2005,28(4):284-286.
［4］Sakai K,Yokoyama A,Kohno N,Hiwada K.Effect of different sensitizing doses of antigen in a murine modle of atopic asthma［J］. Clin Exp Immune, 1999, 118(1): 9-15.
［5］van Oosterhout AJ,Bloksma N. Regulatory T-lymphocytes in asthma［J］.Eur Respir J, 2005, 26(5): 918-932.
［6］王娜，孔宪明，曹兰芳. CD4+CD25+T调节细胞及Foxp3在哮喘中的研究进展［J］.实用儿科临床杂志,2006,21(16): 1103-1105.
［7］李敏,宋丽,张建波,房俊,李兰.糖皮质激素对哮喘小鼠CD4+CD25+调节性T细胞的作用［J］.中国当代儿科杂志,2008,10(4):527-530.
［8］Holgate ST.The epidemic of allergy and asthma［J］.Nature, 1999, 402 (6760 Suppl): B2-B4.
［9］Zhou LF,Yin KS.Toll-like receptors: function and roles in asthma［J］. Chin Med J (Engl), 2004, 117(11): 1709-1715.
［10］苏苗赏,李昌崇.Toll样受体与支气管哮喘免疫调控［J］.国外医学儿科学分册, 2005, 32(2) :92-94.
［11］Shirakawa T,Enomoto T,Shimazu S,Hopkin JM.The inverse association between tuberculin responses and atopic disorder［J］.Science, 1997, 275(5296): 77-79.
［12］Guyot-Revol V, Innes JA, Hackforth S, Hinks T, Lalvani A. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis［J］.Am J Respir Care Med, 2006, 173(7): 803-810.
［13］Hanekom WA.The immune response to BCG vaccination of new-borns［J］.Ann N Y Acad Sci, 2005, 1062: 69-78.
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