白藜芦醇对哮喘小鼠气道炎症及肺组织高迁移率族蛋白B1和基质金属蛋白酶-9表达的影响

Effects of resveratrol on airway inflammation and expression of high mobility group protein B1 and matrix metalloproteinase-9 in lung tissue of asthmatic mice

目的探讨白藜芦醇(RES)对哮喘小鼠气道炎症及肺组织高迁移率族蛋白B1(HMGB1)、基质金属蛋白酶(MMP)-9表达的影响。方法将36只C57BL/6雌性小鼠随机分为对照组、哮喘组和RES干预组,每组各12只。采用卵清蛋白混合液腹腔注射致敏并雾化吸入激发建立哮喘小鼠模型。采用苏木素-伊红染色和过碘酸-雪夫染色观察小鼠气道炎症及黏液分泌情况;酶联免疫吸附试验检测肺泡灌洗液(BALF)中HMGB1和MMP-9蛋白表达水平;分别采用免疫组化染色、逆转录-聚合酶链反应检测肺组织中HMGB1和MMP-9蛋白、mRNA表达水平。结果RES干预组小鼠肺组织炎症病理学评分和基底膜周径标准化的PAS+杯状细胞面积(Apas+/Pbm)均明显低于哮喘组(P<0.05)。哮喘组小鼠BALF中炎症细胞总数、嗜酸性粒细胞计数、巨噬细胞计数、淋巴细胞计数、HMGB1及MMP-9表达水平均高于对照组(P<0.05),而RES干预组小鼠上述指标均低于哮喘组(P<0.05)。对照组小鼠肺组织中HMGB1和MMP-9蛋白及mRNA的表达较少,而哮喘组小鼠肺组织中的表达明显增多,但RES干预组小鼠肺组织中HMGB1和MMP-9蛋白及mRNA的表达水平均明显低于哮喘组(P<0.05)。结论RES可减轻哮喘小鼠气道炎症和气道重塑,其可能机制为通过调节肺组织HMGB1和MMP-9的表达。

Objective To explore the effects of resveratrol on airway inflammation and expression of high mobility group protein B1(HMGB1),matrix metalloproteinase(MMP)-9 in lung tissue of asthmatic mice.Methods Thirty-six C57BL/6 female mice were randomly divided into control group,asthma group and RES treated group,with 12 mice in each group.Asthmatic mice model was established by intraperitoneal injection of ovalbumin mixture to cause allergies and atomization inhalation of ovalbumin mixture to excite.Airway inflammation and mucus secretion condition were observed by hematoxylin-eosin(HE)staining and iodic acid-schiff(PAS)staining.Expression levels of HMGB1 and MMP-9 protein in alveolar lavage fluid(BALF)were detected by enzyme linked immunosorbent assay.Expression levels of HMGB1 and MMP-9 protein,mRNA in lung tissue were examined by immunohistochemical staining and reverse transcription polymerase chain reaction respectively.Results Inflammatory pathology score and the area of goblet cells standarded by perimeter of basement membarane(Apas+/Pbm)in RES treated group were significantly decreased than those in asthma group(P<0.05).Counts of total inflammation cells,eosinophil cells,macrophage cells,lymphocytes,expression levels of HMGB1 and MMP-9 protein in BALF of asthma group were higher than those of control group(P<0.05),while above indexs in RES treated group were lower than those in asthma group(P<0.05).There was a low expression of HMGB1 and MMP-9 protein,mRNA in lung tissue of control group,while expression of above indexes significantly increased,but expression levels of HMGB1 and MMP-9 protein,mRNA in lung tissue of RES treated group were significantly lower than those of asthma group(P<0.05).Conclusion RES can alleviate airway inflammation and airway remodeling in asthmatic mice,the possible mechanism is by regulating expression of HMGB1 and MMP-9 in lung tissue.