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

Effect of macrolides on the syntheses of caveolin-1,PCNA and Bax in lung tissues of asthmatic rats

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 At （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 eomparod to those in the other groups （P = 0.001 for all）, and the synthetic level of PCNA decreased significantly in the interferenee 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-I and Bax （r = 0.837, P = 0.001）. Conclusions The single administration of macrolides or its combination with glucocortieoids 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.