稳定脑肥大细胞减轻脂多糖诱导的肝脏炎症  

Stabilization of brain mast cells alleviates lipopolysaccharide-induced liver inflammation

作　　者：朱友 董洪权[3] 李梦羽 张姝 周希乔[1] ZHU You;DONG Hongquan;LI Mengyu;ZHANG Shu;ZHOU Xiqiao(Department of Gastroenterology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029;Department of Gastroenterology,Jiangbei District of the Affiliated Zhongda Hospital of Southeast University,Nanjing 210044;Department of Anesthesiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Clinical Research Center,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院消化科,江苏南京210029 [2]中大医院江北院区消化内科,江苏南京210044 [3]南京医科大学第一附属医院麻醉科,江苏南京210029 [4]南京医科大学第一附属医院临床医学研究院,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2021年第7期1015-1020,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81570522,81701375);江苏省卫建委强卫工程青年人才(QNRC2016568)。

摘　　要：目的:应用肥大细胞稳定剂观察中枢神经系统中肥大细胞在脂多糖(lipopolysaccharide,LPS)诱导的肝脏炎症中的作用。方法:利用脑立体定位仪在大鼠下丘脑定位注射色甘酸钠以稳定脑肥大细胞。采用苏木精和伊红染色观察肝脏组织的病理改变;酶联免疫吸附试验(ELISA)检测血清肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)和白细胞介素-6(interleukin 6,IL-6)、促甲状腺激素(thyroid stimulating hormone,TSH)、三碘甲状腺原氨酸(triiodothyronine,T3)和甲状腺素(thyroxine,T4)的水平;蛋白免疫印迹分析细胞信号蛋白的表达。结果:脂多糖能够诱导血清TNF-α和IL-6水平升高,导致肝脏病理改变和丝裂原活化蛋白激酶(mitogen activated protein kinases,MAPK)、丝/苏氨酸蛋白激酶(serine-threonine kinase,AKT)和核因子κB(nuclear factor-κB,NF-κB)的信号激活。脑立体定位注射肥大细胞稳定剂能够改善脂多糖诱导的肝脏炎症、抑制MAPK、AKT和NF-κB信号通路在体内的激活,减轻脂多糖引起的外周血和下丘脑中TSH和T3水平下降以及T4水平的升高。结论:中枢神经系统肥大细胞的稳定能够延缓脂多糖诱导的肝脏炎症,该延缓作用有下丘脑-垂体-甲状腺轴参与。Objective:Applied mast cell stabilizers to investigate the role of central nervous system(CNS) mast cells in lipopolysaccharide(LPS)-induced liver inflammation. Methods:Stabilized brain mast cells by site-directed injection of cromolyn in rat right hypothalamus using stereotaxic techniques in vivo. Liver histopathological changes were evaluated by hematoxylin and eosin staining. Tumor necrosis factor α(TNF-α),interleukin 6(IL-6),thyroid-stimulating hormone(TSH),triiodothyronine(T3),and thyroxine(T4)were measured with commercial ELISA kits. Cell signaling proteins were analyzed by Western blot. Results:LPS administration induced increase of serum TNF-α and IL-6 levels,liver pathology and mitogen activated protein kinases(MAPK),serine-threonine kinase(AKT),and nuclear factor-κB(NF-κB)signaling activation. Furthermore,stabilization of CNS mast cells can ameliorate LPS-induced liver inflammation and MAPK,AKT,and NF-κB signaling pathway activation in vivo. Stabilization of CNS mast cells also alleviated LPS-induced decrease of TSH and T3 levels,and increase of T4 level in the peripheral blood and brain hypothalamus. Conclusion:Stabilization of CNS mast cells can delay the pathogenesis of LPS-induced liver inflammation,which is participated by the hypothalamic-pituitary-thyroid axis.

关 键 词：肥大细胞 肝炎 下丘脑-垂体-甲状腺轴 

分 类 号：R575.1[医药卫生—消化系统]