MSR1对矽肺小鼠脂质蓄积和炎性因子分泌的影响研究  

The effect of MSR1 on the secretion of inflammatory factors and lipid accumulation in silicosis mice

作　　者：刘艺 李金城 周昱慧 何海兰 郭灵丽 郝小惠 王宏丽 刘和亮 Liu Yi;Li Jincheng;Zhou Yuhui;He Hailan;Guo Lingli;Hao Xiaohui;Wang Hongli;Liu Heliang(School of Public Health,North China University of Science and Technology,Tangshan 063210;Hebei Key Laboratory of Organ Fibrosis,Tangshan 063210)

机构地区：[1]华北理工大学公共卫生学院,唐山063210 [2]河北省器官纤维化重点实验室,唐山063210

出　　处：《安徽医科大学学报》2023年第11期1928-1933,共6页Acta Universitatis Medicinalis Anhui

基　　金：河北省自然科学基金(编号:H2022209021、H202220-9039);河北省重点研发计划项目(编号:192777129D)。

摘　　要：目的探究A类清道夫受体1(MSR1)在矽肺小鼠肺组织内的表达及其在小鼠单核巨噬细胞(RAW264.7)中介导的炎症和脂质代谢的作用。方法24只C57BL/6雄性小鼠随机分为对照组、染毒7 d组、染毒14 d组和染毒28 d组,每组6只。RAW264.7细胞分为对照组、siRNA-MSR1组、SiO_(2)组、siRNA-MSR1+SiO_(2)刺激组。通过苏木精-伊红(HE)染色和Van Gieson(VG)染色观察小鼠肺组织病理变化;油红O染色镜下观察脂质蓄积情况;免疫组织化学染色(IHC)检测MSR1的表达以及定位;免疫印迹法检测MSR1、炎症因子肿瘤坏死因子(TNF)-α、白介素(IL)-6、IL-1β的表达。结果与对照组相比,HE和VG染色结果显示矽肺小鼠肺组织中炎性细胞聚集,胶原分布增加;IHC结果显示,矽肺小鼠模型中MSR1的表达上调;油红O染色结果显示小鼠肺组织出现大量橙红色脂滴;免疫印迹结果显示,与对照组比较,矽肺小鼠肺组织中MSR1、TNF-α、IL-6、IL-1β表达均上调(P<0.05)。与对照组比较,SiO_(2)细胞刺激组MSR1的表达上调,siRNA-MSR1组的MSR1表达降低(P<0.05),SiO_(2)组细胞内出现橙红色脂滴,siRNA-MSR1+SiO_(2)刺激组脂滴蓄积程度低于SiO_(2)组(P<0.01);ELISA结果显示SiO_(2)细胞刺激组TNF-α、IL-6、IL-1β表达上调(P<0.05)。与SiO_(2)组比较,siRNA-MSR1+SiO_(2)刺激组的TNF-α、IL-6、IL-1β表达下调(P<0.05)。结论MSR1参与了矽肺小鼠肺组织和细胞内脂质成分的调控及炎症因子的释放;抑制MSR1的表达可以拮抗巨噬细胞的炎症反应和脂质异常蓄积。MSR1可能是今后干预矽肺病程进展的潜在治疗靶点。Objective To investigate the expression of class A scavenger receptor 1(MSR1)in the lungs of silicosis mice and its role in inflammation and lipid metabolism mediated by mouse mononuclear macrophages(RAW264.7).Methods 24 C57BL/6 male mice were randomly divided into control group,exposed 7 d group,exposed 14 d group,exposed 28 d group,with 6 mice in each group.RAW264.7 cells were divided into control group,siRNA-MSR1 group,SiO_(2)group and siRNA-MSR1+SiO_(2)stimulation group.The pathological changes of lung tissue in mice were observed by HE and VG staining.Lipid accumulation was observed under oil red O staining microscope.Immunohistochemical staining(IHC)was used to detect the expression and localization of MSR1.The expression of MSR1,tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1βwere detected by Western blot.Results Compared with the control group,HE and VG staining results showed that inflammatory cells gathered and collagen distribution increased in the lung tissue of silicosis mice.Oil red O staining showed that a large number of orange-red lipid droplets appeared in the lung tissue of mice.IHC results showed that the expression of MSR1 was up-regulated in silicosis inflammation stage.Western blot results showed that the expression of MSR1,TNF-α,IL-6 and IL-1βwas up-regulated in silicosis inflammation stage(P<0.05).The expression of MSR1 in the SiO_(2)cell stimulation group was up-regulated(P<0.05),and the expression of MSR1 in the siRNA-MSR1 group decreased(P<0.05),and lipid droplets also appeared in the SiO_(2)cell stimulation group.The accumulation of lipid droplets in siRNA-MSR1+SiO_(2)stimulation group was lower than that in SiO_(2)group(P<0.01).ELISA results showed that the expression of TNF-α,IL-6 and IL-1βin SiO_(2)cell stimulation group was up-regulated(P<0.05).Compared with SiO_(2)group,the expression of TNF-α,IL-6 and IL-1βin siRNA-MSR1+SiO_(2)stimulation group was down-regulated(P<0.05).Conclusion MSR1 is involved in the regulation of lipid components and the release of inflamma

关 键 词：矽肺 炎症反应 脂质代谢 A类清道夫受体 巨噬细胞 MSR1 

分 类 号：R135.2[医药卫生—劳动卫生]