髓系细胞TGF-β1基因缺失增加小鼠对结肠炎的易感性  

TGF-β1 gene deletion of myeloid cells increases the susceptibility to colitis in mice

作　　者：曾志琴 刘巍 罗双慧 胡楚鹏 许宁银 黄安 奚涛[1] 邢莹莹[1] ZENG Zhiqin;LIU Wei;LUO Shuanghui;HU Chupeng;XU Ningyin;HUANG An;XI Tao;XING Yingying(Jiangsu Key Laboratory of Carcinogenesis and Intervention&School of Life Science and Technology,China)

机构地区：[1]中国药科大学生命科学与技术学院中国药科大学江苏省肿瘤发生与干预重点实验室,南京210009

出　　处：《免疫学杂志》2020年第4期312-318,共7页Immunological Journal

基　　金：国家重点研发项目(2017YFD0400303);国家自然科学基金(81502970);江苏省高等学校重点学术项目(PAPD)。

摘　　要：目的探究髓系细胞中TGF-β1基因敲除对葡聚糖硫酸钠(dextran sulfate sodium,DSS)引发的小鼠结肠炎发病进程的影响以及与神经肽因子的关系。方法TGF-β1^+/+LysM-Cre及TGF-β1f/fLysM-Cre小鼠分别分成2组,饮用无菌水的小鼠命名为TGF-β1^+/+LysM-Cre water及TGF-β1f/fLysM-Cre water;饮用含2%DSS无菌水的小鼠命名为TGF-β1^+/+LysM-Cre DSS及TGF-β1f/fLysM-Cre DSS。检测小鼠质量;记录死亡率;测量结肠长度;HE染色检测结肠组织中炎症细胞浸润情况;QRT-PCR及免疫组化检测结肠组织中炎症因子,神经肽及其受体的表达水平。结果TGF-β1^+/+LysM-Cre water及TGF-β1f/fLysM-Cre water小鼠均表征正常;而TGF-β1^+/+LysM-Cre DSS及TGF-β1f/fLysM-Cre DSS小鼠的结肠炎症状明显,此外,相比TGF-β1^+/+LysM-Cre DSS小鼠,TGF-β1f/fLysM-Cre DSS小鼠的质量降低更多,死亡率增加了60%,结肠长度更短,结肠组织炎症细胞浸润更明显,且QRT-PCR及免疫组化结果均显示其炎症因子、神经肽因子及受体表达水平更高。结论髓系细胞敲除TGF-β1会增加小鼠对结肠炎的易感性,神经肽在其中发挥着一定的作用。To investigate the role of myeloid cells-derived TGF-β1 on the pathogenesis of experimental colitis and the roles of neuropeptide factors in this process.The colitis was induced in the littermate TGF-β1^+/+LysM-Cre and TGF-β1f/fLysM-Cre mice.The mice drinking sterile water were named as TGF-β1^+/+LysM-Cre water cohort or TGF-β1f/fLysM-Cre water cohort,while the mice treated with DSS were named as TGF-β1^+/+LysM-Cre DSS or TGF-β1f/fLysM-Cre DSS.The body weight,mortality rates,colon length of the mice were examined;the inflammatory cells infiltrated in colon tissues were detected by hematoxylin-eosin staining.QRT-PCR and immunohistochemistry were used to detect the expression levels of inflammatory factors,neuropeptide and their receptor in colon tissues.Data showed that both TGF-β1^+/+LysM-Cre water and TGF-β1f/fLysM-Cre water cohorts displayed normal phenotypes.The symptoms of colitis were severe in TGF-β1^+/+Lys M-C re DSS and TGF-β1f/fLys M-C re DSS mice.TGF-β1f/fLysMCre DSS cohort displayed more weight loose,mortality rates,colon length shortening and inflammation cells infiltration,as compared with the TGF-β1^+/+LysM-Cre DSS mice.Additionally,increased inflammatory factor,neuropeptide and their receptor were found on the intestinal tissue of TGF-β1f/fLysM-Cre DSS mice.This study highlights that TGF-β1 deletion of myeloid cell increases the susceptibility of mice to colitis,which is associated with the production of neuropeptide.

关 键 词：TGF-Β1 结肠炎 髓系细胞 神经肽因子 

分 类 号：R574.1[医药卫生—消化系统]