摘要
目的 探究沉默SLC26A4对哮喘大鼠气道炎症的影响,并分析其机制。方法 SD大鼠随机分为对照组(Control组)、哮喘组(Asthma组)、哮喘+沉默对照组(Asthma+si-NC组)和哮喘+沉默SLC26A4组(Asthma+si-SLC26A4组),每组10只,采用卵清蛋白致敏和激发建立哮喘大鼠模型,计数大鼠BALF中白细胞总数以及巨噬细胞数、嗜酸性粒细胞数、淋巴细胞数和中性粒细胞数;RT-qPCR检测大鼠肺组织中SLC26A4表达;Western blot检测大鼠肺组织中SLC26A4、PI3K/Akt/NF-κB信号通路相关蛋白、NLRP3炎症小体相关蛋白以及GSDMD-N蛋白表达;HE染色观察大鼠肺组织病理形态变化;ELISA检测大鼠血清和BALF中IL-1β和IL-18水平。结果 沉默SLC26A4改善哮喘大鼠肺组织结构损伤,降低大鼠肺组织中浸润的炎性细胞数量以及BALF中白细胞总数、巨噬细胞数、嗜酸性粒细胞数、淋巴细胞数和中性粒细胞数,并降低大鼠血清和BALF中IL-1β和IL-18水平,下调大鼠肺组织中SLC26A4 mRNA和蛋白以及p-PI3K、p-AKT、p-NF-κB、NLRP3、ASC、cleaved caspase-1和GSDMD-N蛋白表达。结论 沉默SLC26A4改善哮喘大鼠气道炎症,其机制与抑制PI3K/Akt/NF-κB信号通路介导的NLRP3炎症小体激活诱导的焦亡相关蛋白GSDMD-N上调有关。
Objective To explore the effect of silent SLC26A4 on airway inflammation in asthmatic rats and ana-lyze its mechanism.Methods SD rats were randomly divided into control group(control group),asthma group(Asthma group),asthma+silent control group(Asthma+si-NC group)and asthma+silent SLC26A4 group(Asthma+si-SLC26A4 group),with 10 rats in each group.Asthma rat model was established by ovalbumin sensitization and stimula-tion,and the total number of white blood cells,macrophages,eosinophils,lymphocytes and neutrophils in BALF of rats were counted.RT-qPCR was used to detect the expression of SLC26A4 mRNA in rat lung tissue.Western blot was used to de-tect the expressions of SLC26A4,PI3K/Akt/NF-κB signaling pathway related proteins,NLRP3 inflammasome related proteins and GSDMD-N protein in lung tissue of rats.HE staining was used to observe the pathological changes in lung tissues of rats.ELISA was used to detect the levels of IL-1βand IL-18 in serum and BALF of rats.Results Silencing SLC26A4 could improve the structural damage of lung tissue in asthmatic rats,reduce the number of inflammatory cells in-filtrated in lung tissue and the total number of white blood cells,macrophages,eosinophils,lymphocytes and neutrophils in BALF,reduce the levels of IL-lβand IL-18 in serum and BALF,and down-regulate the expressions of SLC26a4 mR-NA and protein and the expressions of p-PI3K、p-AKT、p-NF-κB、NLRP3、ASC、cleaved caspase-1 and GSDMD-N protein in lung tissue of rats.Conclusion Silencing SLC26A4 improves airway inflammation in asthmatic rats,and its mechanism may be related to inhibiting the up-regulation of focal death-related protein GSDMD-N induced by activa-tion of NLRP3 inflammatory corpuscles mediated by PI3K/Akt/NF-κB signaling pathway.
作者
李冬斌
赵睿暄
杨微
曾庆为
LI Dong-bin;ZHAO Rui-xuan;YANG Wei;ZENG Qing-wei(Department of Respiratory and Critical Care Medicine,General Hospital of Northern Theater Command of PLA,Shenyang 110016,China)
出处
《解剖科学进展》
2025年第6期749-752,760,共5页
Progress of Anatomical Sciences
基金
辽宁省科学技术计划项目(2021JH2/10300102)。
