内质网应激相关蛋白在溃疡性结肠炎患者肠黏膜组织中的表达及临床意义OA

Objective To investigate the expression and clinical significance of endoplasmic reticulum stress(ERS)related proteins in intestinal mucosal tissues of ulcerative colitis(UC)patients.Methods A total of 95 patients initially diagnosed with active UC at Beijing Puren Hospital and the Affiliated Hospital of Qingdao University from January 2020 to December 2023 were retrospectively selected as the UC group.Thirty healthy individuals who underwent colonoscopy at the Affiliated Hospital of Qingdao University during the same period served as the control group.Expression levels of ERS-related proteins in intestinal mucosal tissues,including glucose-regulated protein 78(GRP78),phosphorylated protein kinase R-like endoplasmic reticulum kinase(p-PERK),phosphorylated eukaryotic initiation factor 2α(p-eIF2α),activating transcription factor(ATF)4,phosphorylated inositol requiring enzyme 1α(p-IRE1α),and cleaved ATF6,were detected and compared between the two groups using Western blotting.Disease severity of UC was assessed using the modified Mayo score and the Mayo endoscopic score,and expression levels of ERS-related proteins were compared among patients with different disease severity.Prognosis was evaluated based on colonoscopy reexamination results after two months of standardized treatment.Multivariate logistic regression was used to analyze factors influencing the prognosis of UC patients,and ROC curve analysis was employed to assess the predictive performance of these factors for prognosis.Results The expression levels of GRP78,p-PERK,p-eIF2α,ATF4,p-IRE1α,and cleaved ATF6 in the intestinal mucosal tissues of the UC group were significantly higher than those in the control group(all P＜0.01).According to the modified Mayo score,the UC patients were classified into three groups:35 cases with a score of one,39 cases with a score of two,and 21 cases with a score of three.According to the Mayo endoscopic score,the UC patients were classified into three groups:34 cases with a score of one,41 cases with a score of two,and 20 cases with a score of three.The comparison of protein expression levels of GRP78,p-PERK,p-EIF2α,and ATF4 in patients with different disease severity evaluated based on the modified Mayo score or Mayo endoscopic score showed statistically significant differences(all P＜0.05).GRP78(OR=35.909),p-PERK(OR=78 009.922),p-eIF2α(OR=544.575),ATF4(OR=100.148)and C-reactive protein(CRP)(OR=1.254)were independent risk factors for poor prognosis in UC patients(P＜0.05).The AUCs for GRP78,p-PERK,p-eIF2α,ATF4,CRP alone,and their combination in predicting the prognosis of UC patients were 0.702,0.851,0.731,0.801,0.826,0.970,respectively,with the combined model showing the best predictive performance.Conclusion The ERS-related proteins GRP78,p-PERK,p-eIF2α,and ATF4 are upregulated in the intestinal mucosal tissues of UC patients and are associated with increased disease severity and poor prognosis.The combination of these markers with CRP measurement has high predictive value for the prognosis of UC patients.