广藿香酮对COPD小鼠肺部损伤保护作用机制研究

Protective mechanism of pogostone on lung injury in COPD mice

目的研究广藿香酮对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)小鼠肺损伤的保护作用及其机制。方法采用反复香烟烟熏法复制小鼠COPD模型。随机将60只ICR实验小鼠分为对照组、模型组、地塞米松组(1mg/kg)、低剂量广藿香酮组(40mg/kg)、高剂量广藿香酮组(80 mg/kg)。观察各组肺组织的病理学改变,血清白介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α,肺组织中超氧化物歧化酶(SOD)、丙二醛(MDA)的含量。Western blot检测肺组织中Nrf-2内源性抗氧化信号和炎症相关蛋白的表达。结果与模型组比较,地塞米松组和广藿香酮高、低剂量组血清中TNF-α、IL-6、IL-1β和MDA的含量均降低,SOD含量均增加;高剂量广藿香酮组炎症相关蛋白p-IκBα、p-NF-κBp65的表达减少,抗氧化相关蛋白Nrf-2、HO-1的表达增加,差异均有统计学意义(P<0.05)。结论广藿香酮对COPD小鼠肺损伤具有一定的保护作用,其机制可能与抑制氧化应激诱导的炎症反应相关。

Objective To evaluate the protective mechanism of pogostone on lung injury in COPD mice.Methods Firstly,smoking method with cigarette smoke was used to establish the COPD mice model.Secondly,60 ICR mice were randomly divided into five groups,namely,control group,model group,dexamethasone group(1 mg/kg),pogostone small-dose group(40 mg/kg),and pogostone large-dose group(80 mg/kg).Next,all groups were closely followed for pathological changes in the lung tissue.Then the serum interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),lung superoxide dismutase(SOD),and malondialdehyde(MDA)of all groups were measured.Western blot was applied to evaluate the Nrf-2 endogenous antioxidant signaling and inflammation related proteins in lung.Results Compared with those of the model group,the levels of TNF-α,IL-6,IL-1βand MDA in the serum of the dexamethasone group and the pogostone large-dose and small-dose group became lowered,the level of SOD content became higher.The differences were statistically significant(P<0.05).Compared with those of the model group,the expression of inflammatory-related proteins p-IκBαand p-NF-κBp65 decreased in pogostone large-dose group,the expression of Nrf-2 and HO-1 increased in pogostone large-dose group.The differences were statistically significant(P<0.05).Conclusions Pogostone possesses protective effect on lung injury induced by COPD in mice.The underlying mechanism may be related to the regulation of oxidative stress induced inflammation.