基于IRE1α/NF-κB信号通路探讨芪蛭皱肺颗粒对慢性阻塞性肺疾病模型大鼠肺组织炎症损伤的影响OA

Objective To observe the effects of Qizhi Zhoufei Granules on the expression of IRE1α/NF-κB signaling pathway related proteins and inflammatory injury in rats with chronic obstructive pulmonary disease(COPD);To explore its mechanism.Methods The study used a modeling method of cigarette smoke stimulation combined with intratracheal instillation of lipopolysaccharide.Totally 60 SPF-grade Wistar rats were divided into blank group,model group,Bufei Huoxue Capsule group(0.34 g/kg)and Qizhi Zhoufei Granules low-,medium-and high-dosage groups(0.81,1.62,3.24 g/kg)according to the random number table method,with 10 rats in each group.After modeling,Qizhi Zhoufei Granules low-,medium-and high-dosage groups and Bufei Huoxue Capsule group were gavaged with corresponding drug solution respectively,and the blank group and model group were gavaged with normal saline for 28 days.The morphology of lung tissue in rats was observed by HE staining,the serum contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 were detected by ELISA,the mRNA expressions of glucose regulated protein 78(GRP78),inositol demand enzyme 1α(IRE1α)and nuclear factor-κB(NF-κB)p65 were detected by q-PCR,the expressions of GRP78,IRE1α,NF-κBp65 and p-NF-κBp65 proteins in lung tissue were detected by Western blot,immunohistochemical staining was used to detect the distribution and expression of GRP78 in lung tissue.Results Compared with the blank group,the alveolar septum was widened in the model group,local alveolar septum was broken,lymphocyte infiltration was obvious,some alveoli were reduced or even disappeared,the alveolar cavity was compensated for expansion,pulmonary bullae were formed,and obvious lymphocyte infiltration was observed in the bronchial and perivascular fibrous tissues,the scores of peribronchitis,intrabronchial exudation,alveolar injury and total score significantly increased(P<0.01),the contents of TNF-α and IL-6 in serum significantly increased(P<0.05),the mRNA expressions of GRP78,IRE1α and NF-κBp65 in lung tissue significantly increased(P<0.05),the protein expressions of GRP78,IRE1α and p-NF-κBp65 significantly increased(P<0.01),and the positive expression of GRP78 significantly increased(P<0.01).Compared with the model group,pathological injury of lung tissue in rats was reduced in Qizhi Zhoufei Granules medium-and high-dosage groups and Bufei Huoxue Capsule group,the scores of peribronchitis,intrabronchial exudation,alveolar injury and total score decreased(P<0.05,P<0.01),the contents of TNF-α and IL-6 in serum significantly decreased(P<0.05),the mRNA expressions of GRP78,IRE1α and NF-κBp65 in lung tissue significantly decreased(P<0.05),the protein expressions of GRP78,IRE1α and p-NF-κBp65 significantly decreased(P<0.01),and the positive expression of GRP78 significantly decreased(P<0.01).Conclusion Qizhi Zhoufei Granules can inhibit the expression of IRE1α/NF-κB pathway related factors,block the inflammatory cascade mediated by endoplasmic reticulum stress,and improve the lung injury in COPD rats.