【摘要】 目的探究谷氨酰胺对过敏性哮喘小鼠气道重塑模型的治疗作用及其可能机制。方法本实验选取雌性Balb/c小鼠30只,并随机抽取10只为1组,共分为3组,分别为Control组、OVA慢性气道重塑模型组、谷氨酰胺治疗组(750 mg/kg)。在最后一次给药24 h后,给予不同剂量的乙酰胆碱激发并做小鼠气道反应评估;Diff-Quick染色对小鼠肺泡灌洗液BALF中的各类细胞进行细胞计数;HE染色方法观察小鼠肺部组织炎症情况;PAS染色方法查看小鼠肺组织杯状细胞变化;Masson染色方法检测小鼠肺部组织胶原纤维沉积状态;ELISA方法检测小鼠BALF中炎性及促炎细胞因子的含量;Western blot对肺组织中的PERK、eIF2α、ATF4、CHOP、ATF6、IRE1、XBP-1、GRP78含量进行定量分析。结果谷氨酰胺治疗组能够明显降低OVA诱导的哮喘小鼠气道高反应性;谷氨酰胺可以降低哮喘小鼠BALF总细胞及嗜酸性粒细胞、中性粒细胞、淋巴细胞的产生;谷氨酰胺减少哮喘小鼠肺组织炎症细胞渗出、杯状细胞增生以及胶原纤维的沉积;谷氨酰胺能够降低BALF中IL-4、IL-5、IL-13、TNF-α、IL-1β的水平;Western blot结果显示谷氨酰胺能够抑制p-PERK、eIF2α、ATF4、CHOP和ATF6核异位以及IRE1的磷酸化和XBP-1、GRP78的蛋白表达量。结论 OVA诱导的过敏性哮喘能够诱发肺组织产生内质网应激,谷氨酰胺能够通过抑制内质网应激从而减缓气道炎症以及气道重塑,对过敏性哮喘起到治疗保护的作用。更多还原

【Abstract】 To explore the therapeutic effect of glutamine on airway remodeling model of asthmatic mice and its possible mechanism, 30 female Balb/c mice were recruited and randomly divided into control group, OVA airway remodeling model group, and glutamine treatment group(750 mg/kg). Twenty four hours after the last administration,the mice were given different doses of acetylcholine to stimulate the airway reaction. HE, PAS and Masson staining were used to observe lung histopathological changes in mouse lung; the total cells and eosinophil, neutrophil,lymphocyte in BALF were counted by diff-quick staining; ELISA was used to detect the contents of IL-4, IL-5, IL-13, TNF-α, IL-1β in BALF; Western blot was used to quantitatively analyze the contents of PERK, eIF2α, ATF4,CHOP, ATF6, IRE1, XBP-1, GRP78 in lung tissues. Data showed that glutamine treatment significantly reduced the airway hyperresponsiveness induced by OVA in asthmatic mice; glutamine also reduced the exudation of inflammatory cells, proliferation of goblet cells and collagen deposition. Furthermore, glutamine inhibited the generation of eosinophil, neutrophil and lymphocyte, and reduced the levels of IL-4, IL-5, IL-13, TNF-α and IL-1β in bronchoalveolar lavage fluid.Western blot result showed that glutamine inhibited the protein expression of p-PERK, eIF2α, ATF4, CHOP,p-IRE1, XBP-1, GRP78 and nuclear ectopic of ATF6. In conclusion, glutamine can reduce airway inflammation and airway remodeling by inhibiting OVA-induced endoplasmic reticulum stress in allergic asthma, thus plays a protective role in the treatment of allergic asthma.更多还原