ASIC1a对急性肺损伤大鼠内质网应激的影响  

Effects of ASIC1a on the endoplasmic reticulum stress in acute lung injury rats

作　　者：朱月琴 潘学胜 杜娜 刘敬浩 刘兰 吴县 王媛媛[4] 胡成穆[1,2,3] 黄艳 Zhu Yueqin;Pan Xuesheng;Du Na(School of Pharmacy,Anhui Medical Uniersity,Hefei 230032;Anhui Province Key Laboratory of Major Autoimmune Diseases,Hefei 230032;Anhui Institute of Innovative Drugs,Hefei 230032)

机构地区：[1]安徽医科大学药学院,合肥230032 [2]安徽医科大学重大自身免疫性疾病安徽省重点实验室,合肥230032 [3]安徽省创新药物产业共性技术研究院,合肥230032 [4]安徽医科大学第二附属医院药剂科,合肥230601

出　　处：《安徽医科大学学报》2020年第3期396-401,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金杰出青年项目(编号:1908085J30);2019年大学生创新创业训练计划省级立项。

摘　　要：目的探讨酸敏感离子通道-1a对脂多糖(LPS)诱导的急性肺损伤大鼠肺组织内质网应激相关蛋白表达的影响。方法将40只体质量180~220 g的SPF级雄性Sprague Dawley大鼠随机均分为4组:对照组、模型组、阿米洛利组和地塞米松组。观察大鼠的肺组织病理学变化,ELISA法检测血清中白细胞介素-6(IL-6)的表达;实时荧光定量PCR检测葡萄糖调节蛋白78(GRP78)、CCAAT/增强子结合蛋白同源蛋白(CHOP)和丝氨酸/苏氨酸-蛋白激酶/内切核糖核酸酶肌醇需要酶1(IRE-1)、人X盒结合蛋白1(XBP-1)的表达水平;Western blot检测肺组织中GRP78、剪切的半胱胺酸蛋白酶蛋白-12(c-caspase-12)、IRE-1和XBP-1表达水平。结果与对照组相比,模型组肺组织肺泡塌陷,间质性水肿;IL-6的表达上调(P<0.01)。阿米洛利组以及地塞米松组肺组织相关指标改善。Western blot结果提示,模型组的内质网应激相关基因的蛋白表达相比于对照组增加,阿米洛利组内质网应激相关基因的蛋白表达相比于模型组降低(P<0.01)。实时荧光定量PCR结果显示模型组的内质网应激相关基因的mRNA表达相比于对照组增加,阿米洛利组内质网应激相关基因的mRNA表达相比于模型组降低(P<0.01)。结论LPS诱导的大鼠急性肺损伤中ASIC1a的上调可能介导内质网应激反应。Objective To investigate the effect of acid-sensitive ion channel-1 a on the expression of endoplasmic reticulum stress-related protein in rats with acute lung injury induced by lipopolysaccharide(LPS).Methods 40 SPF male Sprague Dawley rats weighing 180~220 g were randomly divided into 4 groups(10 in each group):Control group,Model group,Amiloride group and Dexamethasone(Dex)group.The pathological changes of lung tissue were observed in rats,and the expression of interleukin-6(IL-6)in serum was detected by ELISA.The expres-sion levels of glucose-regulated protein 78(GRP78),C/EBP-homologous protein(CHOP),Inositol-requiring kinase 1(IRE-1)and X box binding protein 1(XBP-1)were detected by Real-time quantitative PCR.GRP78,ccaspase-12,IRE-1αand XBP-1 in lung tissue were detected by Western blot.Results Compared with the Control group,lung tissues in the Model group showed alveolar collapse and interstitial edema;the expression of IL-6 was up-regulated(P<0.01).The expression of indicators related to lung tissue decreased in the amiloride group and the Dex group.Western blot results showed that the protein expression of endoplasmic reticulum stress-related genes in the Model group was increased compared with the Control group,and the protein expression of endoplasmic reticulum stress-related genes in the Amiloride group was lower than that in the Model group(P<0.01).Real-time quantitative PCR results showed that the mRNA expression of endoplasmic reticulum stress-related genes in the Model group was increased compared with the Control group,and the mRNA expression of endoplasmic reticulum stress-related genes in the Amiloride group was lower than that in the Model group(P<0.01).Conclusion Upregulation of ASIC1 a in LPS-induced acute lung injury rats may mediate endoplasmic reticulum stress response.

关 键 词：急性肺损伤 酸敏感离子通道 脂多糖 阿米洛利 内质网应激 

分 类 号：R320.2415[医药卫生—人体解剖和组织胚胎学] R350.99[医药卫生—基础医学]