IL-13对小鼠AGR2表达的影响及其在哮喘气道黏液过度分泌中的作用

Effects of IL-13 on AGR2 expression in lung and the role of AGR2 in mucus overproduction of airways in asthmatic mice

目的研究白细胞介素-13(IL-13)对AGR2mRNA和蛋白在哮喘小鼠肺组织中表达的影响,探讨AGR2在哮喘气道黏液过度分泌中的作用。方法 18只雌性小鼠随机分为哮喘组、对照组和IL-13组,IL-13组于26d-28d激发前经鼻滴入100μg重组小鼠IL-13。收集支气管肺泡灌洗液(BALF)计嗜酸性细胞分类计数。Real time-PCR方法检测肺组织AGR2mRNA表达。免疫组化法分别检测AGR2蛋白和Muc5ac蛋白在小鼠肺组织的表达。结果哮喘组BALF中嗜酸性细胞分类计数(19.1±6.34)%较正常组(0.28±0.29)%明显增多(P<0.01);IL-13组BALF中嗜酸性细胞分类计数(30.05±9.32)%较哮喘组明显升高(P<0.01)。IL-13组小鼠肺组织中AGR2mRNA(1.702±0.046)和蛋白(0.617±0.028)的表达较哮喘组(1.52±0.071,P<0.01;0.505±0.078,P<0.05)升高,IL-13组AGR2mRNA与Muc5ac蛋白的表达水平呈直线正相关(r=0.862,P<0.05);AGR2蛋白与Muc5ac蛋白水平呈直线正相关(r=0.847,P<0.05)。结论 AGR2可能参与了哮喘气道黏液过度分泌发病机制,IL-13可通过上调其表达,进一步促进黏蛋白Muc5ac表达。

Objective To investigate the effects of IL-13 on the expression of AGR2 in the lung,and the role of AGR2 in mucus overproduction of airways in asthmatic mice . Methods 18 BALB/c mice were divided randomly into control, asthmatic and IL-13 groups. The IL-13 group was treated with 100μg re- combinant murine IL-13 by nasal instillation on days 26, 27 and 28. The percentage of eosinophils in BALF of the 3 groups was counted. AGR2 mRNA was detected hy Real-time PCR. The expressions of AGR2 and Muc5ac proteins in the lung were detected by immunohistochemical assay. Results The eosino- phil percentage in BALF of the asthmatic group （19. 1±6.34） % was significantly higher than in the con- trol group （0.28%±0.29%,P〈0.01） ,and also significantly higher in the IL-13 group（30.05±9.32） than in the asthmatic group（P〈0.01）. The expression of AGR2 mRNA（1. 702±0. 046）and protein（0. 617±0. 028）in the IL-13 group were significantly higher than those of the asthmatic group （1.52±0.071 ,P〈 0.01 ;0. 505±0. 078,P〈0.05）. There were positive relationships between AGR2 mRNA and Muc5ac pro- tein （r=0. 862,P〈0.05） ,and between AGR2 protein and MucSac protein （r=0. 847,P〈0.05）. Conclu- sion AGR2 might play a role in mucus overproduction in asthmatic mice. AGR2 gene expression and pro- tein release are up-regulated by IL-13, which promotes the expression of Muc5ac protein.