VIP对LPS应激的小鼠成纤维细胞TREM-2表达的影响及其机制  

Effect of VIP on the expression of TREM-2 in mouse fibroblasts with LPS stress and its mechanism

作　　者：李淑芬[1] 宋卓慧[1] 杨慧慧 刘永平[2] 熊建兵 管茶香[2] 孙国瑛[2,3] LI Shu-fen;SONG Zhuo-hui;YANG Hui-hui;LIU Yong-ping;XIONG Jian-bing;GUAN Cha-xiang;SUN Guo-ying(Department of Physiology,Changzhi Medical College,Changzhi 046000,Shanxi Province,China;Department of Physiology,Xiangya Medical School,Central South University,Changsha 410078,China;Department of Histology and Embryology,School of Medicine,Hunan Normal University,Changsha 410013,China)

机构地区：[1]长治医学院生理学教研室,山西长治046000 [2]中南大学湘雅医学院生理学系,长沙410078 [3]湖南师范大学医学院组织学与胚胎学教研室,长沙410013

出　　处：《中国临床解剖学杂志》2018年第4期402-407,共6页Chinese Journal of Clinical Anatomy

基　　金：国家自然科学基金(81670014);湖南省自然科学基金(2018JJ3368);中南大学博士后基金(160320001);长治医学院科研启动基金项目(QDZ201518)

摘　　要：目的观察血管活性肠肽（vasoactive intestinal peptide,VIP）对脂多糖（lipopolysaccharides,LPS）应激的小鼠成纤维细胞髓样细胞表达触发受体-2（TREM-2）表达的影响,并初步探讨其信号转导通路。方法利用LPS腹腔注射建立急性肺损伤（ALI）小鼠模型;采用VIP慢病毒气管滴注,q PCR检测肺组织TREM-2的表达。选用q PCR和流式细胞术检测VIP对LPS应激的小鼠成纤维细胞TREM-2表达的影响;并观察PKC信号通路阻断剂（H-7）、PKA信号通路阻断剂（H-89）、MAPK信号通路阻断剂（PD98059）和Ca M信号通路阻断剂（W-7）对VIP调控TREM-2表达的影响。结果 ALI时小鼠肺组织TREM-2 m RNA表达降低,而VIP可上调肺组织TREM-2 m RNA的表达。LPS下调小鼠成纤维细胞TREM-2 m RNA的表达,VIP可呈时间依赖性上调TREM-2 m RNA的表达（0、3、6、12和24 h）,且在6 h达到峰值;并呈剂量相关性上调TREM-2 m RNA的表达（10^（-10）、10^（-9）、10^（-8）和10^（-7）mol/L）,以10^（-8）mol/L作用最明显。VIP对LPS应激6 h增加小鼠成纤维细胞TREM-2 m RNA和蛋白表达的效应可被H-7、PD98059以及W-7所阻断。结论 LPS下调小鼠成纤维细胞TREM-2的表达,而VIP可上调LPS应激的小鼠成纤维细胞TREM-2 m RNA的表达,其胞内信号转导途径可能与PKC、MAPK及Ca M有关。Objective To observe the effect of VIP（vasoactive intestinal peptide） on TREM-2 expression in mouse fibroblasts induced by LPS（lipopolysaccharides） and to explore its possible signaling pathway. Methods ALI animal model was established by intraperitoneal injection of LPS, and VIP lentivirus tracheal infusion was used, and the expression of TREM-2 in lung tissue was detected by q PCR.q PCR and flow cytometry were used to detect the effect of VIP on TREM-2 expression in LPS-induced fibroblasts, and to observe the effects of PKC signal pathway blocker（H-7）, PKA signal pathway blocker（H-89）, MAPK signal pathway blocker（PD98059） and Ca M signal pathway blocker（W-7） on the regulation of VIP expression TREM-2. Results The TREM-2 m RNA expression of lung tissue in mice decreased in ALI, while VIP could increase TREM-2 m RNA expression in lung tissue. LPS down-regulated the expression of TREM-2 m RNA in mice fibroblast, and VIP up-regulated the expression of TREM-2 m RNA in a timedependent manner（0 h, 3 h, 6 h, 12 h, 24 h）, and reached the peak at 6 h. VIP dose related with the TREM-2 m RNA expression（10-10 mol/L, 10-9 mol/L, 10-8 mol/L, 10-7 mol/L）. The up-regulation effect of VIP on TREM-2 m RNA and protein expression in mouse fibroblasts（stress by LPS for 6 h） could be blocked by H-7,PD98059, and W-7. Conclusion LPS can down-regulate the TREM-2 expression of mouse fibroblasts,while VIP can up-regulate the expression of TREM-2 in LPS induced fibroblasts, and the intracellular signal transduction pathway may be related to PKC, MAPK and Ca M.

关 键 词：急性肺损伤 髓样细胞表达的触发受体-2 血管活性肠肽 脂多糖 成纤维细胞 

分 类 号：R332.2[医药卫生—人体生理学]