摘要
目的探讨瞬时感受器电位香草酸受体4(TRPV4)在脂多糖(LPS)诱导的急性肺损伤(ALI)的病理生理中的作用。方法采用腹腔注射LPS建立小鼠ALI模型。6~8周BALB/c雌性小鼠随机分为4组:对照组、LPS组、LPS+GSK2193874组和LPS+DMSO组。测定肺湿/干重比值、肺泡灌洗液中白细胞计数;酶联免疫吸附试验检测肺组织及肺泡灌洗液中白介素6(IL-6)、IL-1β、肿瘤坏死因子α、IL-18;使用免疫组织化学方法和蛋白印迹法检测肺组织中TRPV4的表达。结果与对照组比较,LPS组小鼠肺组织中TRPV4表达增多;TRPV4特异性抑制剂GSK2193874可以减轻LPS诱导的ALI小鼠模型的肺部炎症,使肺湿/干重比值、肺泡灌洗液中白细胞计数降低,下调IL-6、IL-1β、肿瘤坏死因子α、IL-18等细胞因子。结论阻断TRPV4信号可以减轻ALI/急性呼吸窘迫综合征炎症水平,TRPV4未来可能成为ALI治疗的一个新的靶点。
Objective To investigate the role of transient receptor potential vanilloid 4 (TRPV4) in the pathophysiology of acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Methods ALI model was established by intraperitoneal injection of LPS.Female 6-8 weeks old BALB/c mice were randomly divided into four groups: control group, LPS group, LPS+ GSK2193874 group and LPS+ DMSO group.The wet/dry weight ratio of lung and white blood cell count in bronchoalveolar lavage fluid (BALF) were detected.Interleukins-6 (IL-6), IL-1β, tumor necrosis factor-α, and IL-18 in lung tissue and BALF were detected by enzyme linked immunosorbent assay.Immunohistochemistry and Western blot were used to detect the expression of TRPV4 in lung tissue. Results Compared with control group, the expression of TRPV4 was increased in the lung tissue of LPS group.GSK2193874, TRPV4 specific inhibitor, could alleviate lung inflammation induced by LPS, reduce the count of white blood cells in BALF, the wet/dry weight ratio of lung, and decrease the levels of IL-6, IL-1β, tumor necrosis factor-α, IL-18 in BALF and lung tissue. Conclusions Blockade of TRPV4 signaling can attenuate the inflammation of ALI/acute respiratory distress syndrome and TRPV4 may become a new target for ALI therapy in the future.
作者
钟景良
姚慧文
林锦锋
梁锦堂
李姝君
Zhong Jingliang;Yao Huiwen;Lin Jinfeng;Liang Jintang;Li Shujun(Department of Intensive Care Unit, Xinhui People' s Hospital, Jiangmen 529100, China;Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China)
出处
《国际呼吸杂志》
2019年第13期968-972,共5页
International Journal of Respiration
