大环内脂类药物对哮喘大鼠肺组织窖蛋白-1、细胞增殖核抗原和Bax表达的影响

摘要

目的 研究大环内脂类药物对哮喘大鼠肺组织窖蛋白-1(caveolin-1,Cav-1)、细胞增殖核抗原(PCNA)和Bax表达的影响,以及Cav-1与PCNA、Bax表达的关系.方法 以卵蛋白致敏制作大鼠哮喘模型,将大鼠分为5 组:对照组、哮喘模型组、干预组A1(红霉素)、干预组A2(地塞米松)及干预组A3(红霉素 + 地塞米松).应用量子点免疫荧光组织化学方法对Cav-1、PCNA和Bax蛋白表达进行定量检测.结果 模型组Cav-1蛋白表达与其他各组相比均显著下降(P ＜ 0.01),干预组A3上调Cav-1蛋白表达的效果显著优于干预组A1、A2(P ＜ 0.01).模型组与其他各组分别相比,PCNA蛋白阳性表达均显著增加(P ＝ 0.001);干预组A3与对照组相比,PCNA 蛋白阳性表达显著降低(P ＝ 0.006).干预组A1、A2、A3分别与对照组、模型组相比,Bax蛋白阳性表达的差异均有统计学意义(P ＝ 0.001),但干预组A1、A2、A3之间分别相比,差异均无统计学意义 (P ﹥0.05).Cav-1蛋白与 PCNA蛋白表达之间呈显著负相关(r ＝ -0.803,P ＝ 0.001);Cav-1和Bax蛋白表达之间呈显著正相关(r ＝ 0.837,P ＝ 0.001).结论 大环内脂类药物可单用或协同糖皮质激素通过上调肺组织Cav-1的表达来促进细胞凋亡和抑制增殖而发挥抗炎作用.%Objective To investigate the effect of macrolides on the synthetic levels of caveolin-1 ( Cav-1).PCNA and Bax in the lung tissue of asthmatic rats， and the relationship of Cav-1 with the syntheses of either PCNA or Bax.Methods SD rats were divided into five groups, and consisting of the control group, the model group, the interference group A, ( erythromycin) , the interference group A2 ( dexamesone) and the interference group A3 (erythromycin + dexamesone).Asthmatic rat models were established by the repeated ovalbumin sensitivity.The synthetic levels of Cav-1.PCNA and Bax were detected by the quantum dots immunofluorescence histochemistry.Results The synthetic level of Cav-1 in the model group was obviously lower than those in the other groups (P ＜ 0.01 for all).The synthetic level of Cav-1 was significantly up-regulated in the interference group A3 compared to those in the interference groups A1 and A2 (P ＜ 0.01 for all).The synthetic level of PCNA increased significantly in the model group compared to those in the other groups (P = 0.001 for all) , and the synthetic level of PCNA decreased significantly in the interference group A3 compared to that in the control group (P = 0.006).The differential synthetic level of Bax was observed between three interference groups and either the control group (P = 0.001 for all) or the model group (P =0.001 for all) , respectively.There were a negative correlation between the syntheses of Cav-1 and PCNA (r = -0.803.P = 0.001) , and a positive correlation between the syntheses of Cav-1 and Bax (r = 0.837, P = 0.001).Conclusions The single administration of macrolides or its combination with glucocorticoids play an anti-inflammatory role by up-regulating the synthesis of Cav-1 in the lung tissue , which can promote the cell apoptosis and inhibit the cell proliferation.