基于内质网应激PERK-eIF2α-ATF4-CHOP信号通路 探讨平喘宁对寒哮大鼠气道炎症的影响  

Effect of Pingchuanning on Airway Inflammation in Rats with Cold-induced Asthma:A Study Based on the Endoplasmic Reticulum Stress PREK-elF2α-ATF4-CHOP Signaling Pathway

作　　者：乔佳乐 刘家鑫 王月阳 叶卫东 袁亚美[1] 方向明[1] QIAO Jiale;LIU Jiaxin;WANG Yueyang;YE Weidong;YUAN Yamei;FANG Xiangming(Anhui University of Chinese Medicine,Anhui Hefei 230012,China)

机构地区：[1]安徽中医药大学,安徽合肥230012

出　　处：《安徽中医药大学学报》2025年第2期93-99,共7页Journal of Anhui University of Chinese Medicine

基　　金：安徽省高校自然科学研究重大项目(2024AH040157);2021年高校学科(专业)拔尖人才学术资助项目(gxbjZD2021054)。

摘　　要：目的探讨平喘宁基于蛋白激酶R样内质网激酶(protein kinase R like endoplasmic reticulum kinase,PERK)-真核翻译起始因子2α亚基(eukaryotic translation initiation factor 2 subnit alpha,eIF2α)-活化转录因子4(activating transcription factor 4,ATF4)-CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)信号通路改善寒哮大鼠气道炎症的机制。方法将70只SD大鼠随机分为空白组、模型组、平喘宁组、抑制剂组、平喘宁+抑制剂组、地塞米松组、桂龙咳喘宁组,每组10只;除空白组外,其余6组大鼠采用卵清蛋白+AL(OH)3联合冷刺激复制寒哮大鼠模型;空白组、模型组大鼠给予生理盐水灌胃,其余各治疗组给予相应药物溶液灌胃。观察和记录大鼠的呼吸、精神状态、毛色、活动量、食量、大便形态等情况;HE染色法观察大鼠肺组织病理变化,PAS染色法观察大鼠肺组织杯状细胞及黏液变化;ELISA法检测大鼠肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中白细胞介素(interleukin,IL)-5和免疫球蛋白E(immunoglobulin E,IgE)水平;Western blot法检测大鼠肺组织中PERK-eIF2α-ATF4-CHOP信号通路相关蛋白表达水平;RT-PCR法检测大鼠肺组织PERK-eIF2α-ATF4-CHOP信号通路相关蛋白mRNA表达水平。结果与空白组比较,模型组大鼠出现呼吸频次加快、精神状态不佳、聚集蜷缩、毛色枯槁无光泽、食量下降、大便溏薄等表现;支气管管腔狭窄,炎症细胞浸润明显,分泌物增多,气道上皮杯状细胞增生明显;BALF中IL-5、IgE水平显著升高(P<0.05);肺组织中PERK-eIF2α-ATF4-CHOP信号通路相关蛋白及其mRNA表达水平显著升高(P<0.05)。与模型组比较,各治疗组大鼠呼吸频次稍减,精神状态良好,活动增多,食量增加;支气管管腔狭窄,炎症细胞浸润,分泌物增多和杯状细胞增生等情况均好转;BALF中IL-5、IgE水平显著降低(P<0.05);肺组织中PERK-eIF2α-ATF4-CHOP信号通路相关蛋白及Objective To investigate the mechanism of Pingchuanning improving airway inflammation in rats with cold-induced asthma based on the protein kinase R like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2 subunit alpha(eIF2α)-activating transcription factor 4(ATF4)-CCAAT/enhancer-binding protein homologous protein(CHOP)signaling pathway.Methods A total of 70 Sprague-Dawley rats were randomly divided into blank group,model group,Pingchuanning group,inhibitor group,Pingchuanning+inhibitor group,dexamethasone group,and Guilong Kechuanning group,with 10 rats in each group.All rats except those in the blank group were given ovalbumin(OVA)+AL(OH)3 combined with cold stimulation to establish a rat model of cold-induced asthma;the rats in the blank group and the model group were given normal saline by gavage,and those in the other groups were given the corresponding drug solution by gavage.General status was recorded for the rats in each group,including respiration,spirit,hair color,activity,food consumption,and stool;HE staining was used to observe lung histopathological changes,and PAS staining was used to observe the changes in goblet cells and mucus in lung tissue;ELISA was used to measure the levels of interleukin-5(IL-5)and immunoglobulin E(IgE)in bronchoalveolar lavage fluid(BALF);Western blot was used to measure the expression levels of proteins associated with the PERK-eIF2α-ATF4-CHOP signaling pathway,and RT-PCR was used to measure the mRNA expression levels of these proteins in lung tissue.Results Compared with the blank group,the model group had increased respiratory frequency,poor mental status,huddling and curling up,withered and dull hair,reduced food consumption,and thin sloppy stool,as well as bronchial lumen stenosis,marked inflammatory cell infiltration,increased secretions,and obvious goblet cell hyperplasia in the airway epithelium,and there were significant increases in the levels of IL-5 and IgE in BALF(P<0.05)and the protein and mRNA expression levels of the proteins a

关 键 词：寒哮 平喘宁 内质网应激 PERK-eIF2α-ATF4-CHOP信号通路 气道炎症 

分 类 号：R256.12[医药卫生—中医内科学] R562.25[医药卫生—中医学]