烟雾所致轻度稳定期COPD小鼠肺组织中MRP1表达增加与Nrf2信号通路有关

目的探讨Nrf2信号通路对烟雾致轻度稳定期COPD小鼠肺组织中MRP1表达的影响。方法被动香烟烟吸法建立轻度COPD小鼠模型,检测肺功能;病理切片观察肺组织病理学改变;免疫组化及Western blot检测相关蛋白在肺组织中的表达水平。结果与正常组相比,野生型(WT)及Nrf2^-/-模型组各肺功能指标明显降低;并且Nrf2^-/-模型组与WT模型组相比,各肺功能指标的下降更为明显。HE染色结果显示,WT及Nrf2^-/-模型小鼠肺泡中均发生弥漫性炎症反应,肺泡支气管结构受损,并且在Nrf2^-/-模型小鼠中病理改变更为明显。免疫组化及Western blot结果显示,与WT正常组相比,MRP1在Nrf2^-/-正常组小鼠肺组织中的表达明显减少;被动香烟烟吸后,与WT正常组相比,MRP1、Nrf2、HO-1在WT模型组中的表达明显增多,但是与Nrf2^-/-正常组相比,在Nrf2^-/-模型组中MRP1的表达并未发生明显改变。结论

MRP1 is up-regulated in lung tissues of mildly stable COPD mice induced by smoke,Nrf2 pathway may be involved

Aim To investigate the effect of Nrf2 pathway on the expression of MRP1 in mildly stable COPD mice. Methods The mild COPD mouse model was established by passive cigarette smoking. The pathological changes of lung tissues were examined by HE staining. Immunohistochemistry and Western blot were used to detect the protein expression of MRP1, Nrf2 and HO-1. Results Compared with normal group, each lung function index of the mild-moderate COPD model group was significantly lower, but compared with wide type(WT) model group, the reduction was more significant in Nrf2^-/- model group. HE results showed diffuse inflammatory reaction and alveolar bronchial structure damage in alveolar of WT and Nrf2^-/- model mice, and it was more pronounced in Nrf2^-/- mice. Immunohistochemistry and Western blot results showed that the expression of MRP1 in lung tissue of Nrf2^-/- normal mice was significantly reduced compared with the normal WT group. After passive cigarette smoking, The expression of MRP1, Nrf2 and HO-1 in WT model group increased significantly, but compared with Nrf2^-/- normal mice, there was no significant change in the expression of MRP1 in Nrf2^-/- model group. Conclusions Mildly stable COPD mice may counteract the xenobiotic damage caused by cigarette smoke through up-regulating the expression of MRP1 protein, which may be associated with Nrf2 signaling activation.