CpG ODN对卵清蛋白致敏的哮喘小鼠模型的免疫调节作用研究

Effect of CpG oligodeoxynucleotides in OVA antigen induce allergic airway reaction in mice

[目的]研究寡核苷酸免疫刺激序列CpGODN(CpGOligodeoxyneucleotide)对卵清蛋白(OVA)致敏哮喘小鼠的免疫调节作用,探讨哮喘的非激素治疗方法。[方法]以OVA免疫BALB/c小鼠,致敏前和致敏阶段腹腔注射CpGODN ,分别用地塞米松和生理盐水作为激素治疗组和哮喘对照组。流式细胞仪检测各组哮喘小鼠的外周血T淋巴细胞亚群;ELISA法检测各组小鼠血清IL - 4 ,IFN -γ,Ig -E水平;HE染色观察各组哮喘小鼠肺组织病理变化。[结果]与哮喘对照组相比,CpG组能明显降低血清IL - 4水平,NS组:(10 6 .97±13.4 0 ) pg/mL ,CpG组:(87.6 9±13.2 5 )pg/mL ;降低血清Ig -E水平,NS组:(4.78±1.6 5 )IU/mL ,CpG组:(3.5 2±0 .2 3)IU/mL(P <0 .0 5 ) ;增加血清IFN -γ含量,NS组:(34.76±1.5 1) pg/mL ,CpG组:(49.93±9.18) pg/mL(P <0 .0 5 ) ;上调CD4 /CD8的比值,NS组:(3.5 3±0 .37) ,CpG组:(3.73±0 .5 5 ) (P <0 .0 5 ) ;CpG组和地塞米松组均能抑制肺组织中嗜酸细胞的浸润(P <0 .0 5 )。[结论]CpGODN能有效促进哮喘小鼠体内TH2反应向TH1反应,可作为哮喘的预防和治疗的非激素手段。

Objective To investigate the effect of CpG-motifoligodeoxy nucleotides (CpG ODN) on the antigen (OVA) induced allergic airway reaction in mice. [Methods] The asthma model was set up in the BALB/c mice with OVA, Before the antigen insensitization stage, CpG ODN、Anaflogistico and NS were used intra peritoneal. During the state of antigen insensitization,three groups did the same processing. [Results] Compared with the NS control, coadministration of CpG ODN insensitization phase significant reduced the serologic concentrations of IL-4, NS group:(106.97±13.40) pg/mL, CpG group: (87.69±13.25) pg/mL;reduce the serologic concentrations of Ig-E, NS group:(4.78±1.65) IU/mL,CpG group:(3.52±0.23) IU/mL(P<0.05)and increased of IFN-γ level in serum, NS group: (34.76±1.51) pg/mL, CpG group: (49.93±9.18) pg/mL (P<0.05). CpG ODN group updated the serologic CD4/CD8 ratio from (3.53±0.37) to (3.73±0.55)(P<0.05). Coadministration of CpG ODN also reduced the percent of EOS in lung tissue (P<0.05). [Conclusion] This study suggests that in-traperitoneal coadministration of CpG ODN enhances Th1 cytokine such as IL-4 and Ig-E expression, down-regulates Th2 cytokine (IFN-γ) expression. It plays an important role of immunomodulation on Th1/Th2. This study also suggests that CpG ODN immunization can be an effective non-hormone therapy for asthma.