HSF1通过抑制中性粒细胞浸润减轻LPS诱导的小鼠急性肺损伤  

HSF1 attenuates LPS-induced acute lung injury in mice by suppressing neutrophil infiltration

作　　者：肖归 陈广文[1] 李涛[3] 张华莉[1] 王慷慨[1] 刘梅冬[1] 刘可[1] 肖献忠[1] XIAO Gui;CHEN Guang-wen;LI Tao;ZHANG Hua-li;WANG Kang-kai;LIU Mei-dong;LIU Ke;XIAO Xian-zhong(Department of Pathophysiology,Xiangya School of Medicine,Central South University,Changsha 410008,China;De-partment of International School of Nursing,Hainan Medical University,Haikou 571199,China;Department of Patho-physiology,Medical College of Jiaying University,Meizhou 514000,China)

机构地区：[1]中南大学湘雅医学院病理生理学系,湖南长沙410008 [2]海南医学院国际护理学院,海南海口571199 [3]嘉应学院医学院病理学与病理生理学教研室,广东梅州514000

出　　处：《中国病理生理杂志》2022年第1期26-32,共7页Chinese Journal of Pathophysiology

基　　金：海南省自然科学基金资助项目(No.819QN229);国家自然科学基金资助项目(No.81671895,No.81871610)。

摘　　要：目的:探讨热休克因子1(HSF1)是否通过抑制中性粒细胞浸润减轻LPS诱导的小鼠急性肺损伤(ALI)及其分子机制。方法:采用气管滴注脂多糖(LPS)的方法制备小鼠ALI模型,采用流式细胞术检测HSF1野生型(HSF1^(+/+))小鼠和HSF1敲除(HSF1^(-/-))小鼠LPS处理后12、24和36 h支气管肺泡灌洗液(BALF)中性粒细胞比例和表达趋化因子受体XCR-1的中性粒细胞比例;采用免疫荧光法检测HSF1^(+/+)和HSF1^(-/-)小鼠上述时点肺组织中性粒细胞含量;运用ELISA方法检测不同时点血清、肺组织及BALF中趋化因子配体XCL-1的浓度。结果:流式细胞术结果显示,HSF1^(-/-)+LPS组BALF中的中性粒细胞百分率和中性粒细胞表面XCR-1表达水平均高于HSF1+/++LPS组,LPS处理后24 h达到高峰(P<0.05);肺组织免疫荧光观察结果显示,HSF1^(-/-)+LPS组的中性粒细胞数目均多于HSF1^(+/+)+LPS组,以LPS处理后24 h最多;HSF1^(-/-)+LPS组血清、BALF和肺组织中XCL-1浓度均显著高于HSF1^(+/+)+LPS组(P<0.05)。结论:HSF1可能通过抑制XCL-1/XCR-1这对趋化因子配体/受体的表达,抑制了中性粒细胞的浸润,从而减轻LPS所致的小鼠ALI。AIM:To explore whether heat shock factor 1(HSF1)reduces acute lung injury(ALI)induced by lipopolysaccharide(LPS)in mice by inhibiting neutrophil infiltration and its molecular mechanism.METHODS:The model of ALI in mice was prepared by endotracheal infusion of LPS. The percentages of neutrophils and chemokine receptor XCR-1-expressing neutrophils in bronchoalveolar lavage fluid(BALF)of HSF1 wild-type(HSF1^(+/+))mice and HSF1 knockout(HSF1^(-/-))mice at 12 h,24 h and 36 h after LPS treatment were analyzed by flow cytometry. Immunofluorescence staining was used to observe neutrophil content in lung tissues of HSF1^(+/+)and HSF1^(-/-)mice at the above time points.The concentrations of chemokine XCL-1 in serum,lung tissue and BALF at the above time points were measured by ELISA.RESULTS:The results of flow cytometry showed that the percentage of neutrophils and the expression of XCR-1 on neutrophils in BALF of the mice in HSF1^(-/-)+LPS group were higher than those in HSF1^(+/+)+LPS group,and reached the peak at 24 h after LPS treatment(P<0. 05). The results of immunofluorescence showed that the number of neutrophils in lung tissue of the mice in HSF1^(-/-)+LPS group was larger than that in HSF1^(+/+)+LPS group,and was the largest at 24 h after LPS treatment. The concentrations of XCL-1 in serum,BALF and lung tissue of the mice in HSF1^(-/-)+LPS group were significantly higher than those in HSF1^(+/+)+LPS group(P<0. 05).CONCLUSION:Transcription factor HSF1 may inhibit the infiltration of neutrophils by inhibiting the expression of XCL-1/XCR-1,thereby reducing ALI in mice caused by LPS.

关 键 词：急性肺损伤 热休克因子1 中性粒细胞 XCR-1蛋白 XCL-1蛋白 

分 类 号：R363[医药卫生—病理学] R563[医药卫生—基础医学]