基于GRP78-PERK-CHOP信号通路探讨参芪调肾方对COPD肺肾气虚证大鼠内质网应激的影响OA

Objective To explore the mechanism by which Shenqi Tiaoshen Formula(参芪调肾方,SQTSF)regulates the GRP78/PERK/CHOP pathway to alleviate inflammatory response,endoplasmic reticulum stress,and apoptosis in rats with COPD and lung-kidney qi deficiency syndrome.Methods Thirty-six male SD rats were randomly divided into normal group,COPD model group,low/medium/high-dose SQTSF groups,and aminophylline group.The COPD lung-kidney qi deficiency syndrome model was established by cigarette smoke along with LPS airway instillation and swimming combined with sodium hydrocortisone succinate injection.The corre-sponding drugs were administered to each group from day 30,once daily for 3 weeks.HE staining was used to observe morphological changes in lung tissue;lung function was measured;levels of TNF-α,IL-1β,CXCL1,and CCL22 were detected by ELISA;expression levels of GRP78,PERK,and CHOP proteins were assessed by immunohistochemistry(IHC);morphological changes of the endoplas-mic reticulum in lung tissue were observed by transmission electron microscopy(TEM);expression of GRP78,p-PERK,p-eIF2α,ATF4,and CHOP proteins was detected by Western blot(WB);and the apoptosis rate of lung cells was determined by TUNEL staining.Results Compared with the normal group,the model group showed inflammatory infiltration,disappearance of alveolar septa,decreased lung function-related indicators,increased inflammatory factors,expanded and degranulated endoplasmic reticulum,high expression of GRP78,p-PERK,p-eIF2α,ATF4,and CHOP proteins by IHC and WB,and increased apoptosis rate(P<0.05);all the above indi-cators were alleviated in the SQTSF groups(P<0.05).Conclusion The SQTSF may alleviate the inflammatory response in COPD rats,possibly by regulating the GRP78/PERK/CHOP pathway to inhibit endoplasmic reticulum stress and apoptosis.