氨溴索对吸烟大鼠肺组织激活蛋白-1、铜锌超氧化物歧化酶表达的影响

Effect of ambroxol on expression of AP-1 and CuZn-SOD in lung of smoking rats

目的通过研究氨溴索对吸烟大鼠肺组织中激活蛋白-1(AP-1)、铜锌超氧化物歧化酶(CuZn-SOD)表达的影响,探讨氨溴索在慢性阻塞性肺疾病(COPD)抗氧化治疗中的作用及其机制。方法健康雄性Wistar大鼠30只随机分为对照组、吸烟组、氨溴索组,分别采用原位杂交半定量技术、免疫组织化学法和免疫细胞化学法检测支气管上皮细胞及肺泡巨噬细胞中AP-1(c-jun和c-fos亚单位)和CuZn-SOD mRNA及其蛋白的表达水平。结果吸烟组大鼠支气管上皮细胞和肺泡巨噬细胞c-jun、c-fos、CuZn-SOD mRNA及其蛋白表达水平明显高于对照组(均P<0.05);氨溴索组c-jun、c-fos mRNA及其蛋白、CuZn-SOD mRNA表达水平明显低于吸烟组(均P<0.01),而CuZn-SOD蛋白表达水平与其他两组相比无统计学差异(P>0.05)。结论氨溴索可以降低吸烟大鼠肺组织AP-1 mRNA及其蛋白和CuZn-SOD mRNA的表达,其可能通过降低AP-1的表达在COPD治疗中发挥一定的抗氧化作用。

Objective To explore the role of ambroxol in the course of antioxidant therapy in chronic obstructive pulmonary disease（COPD）by investigating its effect on expression of active protein-1（AP-1）and CuZn-superoxide dismutase（CuZn-SOD）in lung of smoking rats.Methods Thirty Wistar rats were divided into 3 groups：control group,smoking group and ambroxol treatment group.The expression of AP-1,CuZn-SOD mRNA and their proteins were detected by in situ hybridization,immunohistochemical method and immunocytochemical method,respectively.Results The expression of c-jun,c-fos,CuZn-SOD mRNA and their proteins in bronchial epithelia and alveolar macrophage in smoking group increased significantly as compared to control group（P〈0.05）.While the expression of c-jun,c-fos mRNA and their proteins,CuZn-SOD mRNA in ambroxol treatment group decreased significantly as compared to smoking group（P〈0.01）.But the expression of CuZn-SOD protein had no significant difference between ambroxol treatment group and smoking group.Conclusion The results indicate that ambroxol may play a role in the antioxidant therapy of COPD through downregulating the expression of AP-1.