哮喘大鼠肺组织Ca^2＋/CaN-NFATc活性及其与TH1/TH2失衡的关系

目的 探究哮喘大鼠肺组织Ca^2＋/CON-NFATc的活性及其与TH1/TH2失衡的关系.方法 24只Wistar大鼠随机分为哮喘组和对照组,12只/组.用鸡卵白蛋白（OVA）溶液致敏和激发复制大鼠哮喘模型.Maclab系统记录分析大鼠肺功能;HE染色观察气道炎症并测量气道管壁厚度;检测肺组织钙含量、CaN活性、去磷酸化NFATc蛋白的表达及IL-4、IL-2的含量.结果 与对照组相比,哮喘组大鼠支气管管壁厚度明显增加（t=-7.99,P〈0.01）;气道阻力和呼吸频率增加（t=2.59,P〈0.05;t=7.94,P〈0.01）,每分通气量减少（t=6.87,P〈0.01）;与对照组相比,哮喘组大鼠肺组织中IL-4含量和IL-4/IL-2比值增高（t=-8.69,11.40,P〈0.01）,而IL-2含量降低（t=8.29,P〈0.01）;与对照组相比,哮喘组大鼠肺组织中CaN活性和去磷酸化NFATc蛋白的相对表达量均增加（t=-2.91,-22.45,P〈0.01）,而肺组织钙含量降低（t=4.75,P〈0.01）;肺组织中CaN活性与去磷酸化NFATc蛋白的相对表达量呈正相关（r=0.39,P〈0.05）;去磷酸化NFATc蛋白的相对表达量与IL-4/IL-2比值呈正相关（r=0.83,P〈0.01）;而肺组织中IL-4/.IL-2比值与大鼠支气管管壁厚度成正相关（r=0.84,P〈0.01）.结论 哮喘大鼠肺组织中CaN-NFATc的活性增加,其活性的增加可促进IL-4/IL-2比值增加,推测CaN-NFATc信号通路可能参与了哮喘大鼠肺组织TH1/TH2失衡的形成.

The activity of Ca2+ /CaN-NFATc and its association with the imbalance of TH1/ TH2 in asthmatic rat lungs

Objective To evaluate the activity of Ca2+ /CaN-NFATc, and study its association with the imbalance of TH1/ TH2 in asthmatic rat lungs. Methods Twenty-four Wistar rats were random divided to the asthma group and control group, twelve rats each group. The rats were sensitized and challenged with ovalbumin to establish the asthmatic model. The pulmonary function of rats was surveyed and evaluated u-sing Maclab system. Airway inflammation and the thickness of bronchial wall ( WAt/Pi) were observed by H. E staining. The quantity of Ca2+ , the activity of CaN , the protein expression of dephosphorylated NFATc and the level of IL-4 and IL-2 were assayed.Results Compared with control group, the thickness of bronchial wall was significantly increased ( t = -7. 99, P <0. 01), the airway resistance was higher( t = 2.59, P <0.05) and the respiration frequency was faster( t =7.94, P <0.01) ,but the minute ventilation volume was lower( t =6. 87, P <0.01) in asthma group. The levels of IL-4 and the IL-4/ IL-2 ratio in rat lungs of asthma group were significantly higher than those in control group ( t = -8.69, P <0. 01; t = 11.40, P <0. 01 .respectively) , however, the levels of IL-2 in asthma group were lower than that in control group ( t =8. 29, P <0. 01). The activity of CaN and the protein expression of dephosphorylated NFATc in asthma group were higher than those in control group( t = -2. 91, P <0.01; t = -22.45, P <0.01,respectively) ,but the quantity of Ca2+ in asthma group was lower than that in control group( t =4. 747, P < 0.01). There wag a positive correlation between the activity of CaN and the protein expression of dephos-phorylated NFATc( r =0. 39, P <0.05) ,so did between the protein expression of dephosphorylated NFATc and the IL-4/ IL-2 ratio( r =0. 83-, P <0.01) ,and the same between the thickness of bronchial wall and the IL-4/ IL-2 ratio( r = 0. 84, P < 0.01). Conclusions The activity of CaN-NFATc was increased in rat lungs of asthma group, and the rising of which might increase the ratio IL-4/ IL-2. Thus, the signal of CaN-NFATc probably took part in the imbalance of TH1/ TH2 in asthmatic rat lungs.