TAM受体酪氨酸激酶在溃疡性结肠炎中的相关性研究  

Correlation Analysis of TAM Subfamily of Receptor Tyrosine Kinases in Ulcerative Colitis

作　　者：叶艳 顾丹丹 魏文娟 缪佳蓉[1] YE Yan;GU Dandan;WEI Wenjuan;MIAO Jiarong(Department of Gastroenterology,First Affiliated Hospital of Kunming Medical University,Yunnan Province Clinical Research Center for Digestive Diseases,Kunming,650032)

机构地区：[1]昆明医科大学第一附属医院消化内科、云南省消化系统疾病临床医学研究中心,650032

出　　处：《胃肠病学》2022年第5期257-262,共6页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金(82260107);云南省兴滇英才支持计划“名医”专项(RLMY20220010);云南省高层次卫生技术人才培养项目(H-2018040)。

摘　　要：背景:TAM受体(Tyro3、Axl和Mertk)作为受体酪氨酸激酶亚家族之一,是一种细胞内负反馈调节因子,在调节炎症和免疫反应中发挥重要作用。目的:研究溃疡性结肠炎(UC)患者的血清和肠黏膜TAM受体表达及其临床价值。方法:纳入昆明医科大学第一附属医院2020年6月—2021年5月初诊活动期UC患者45例,同期健康体检者15例作为对照组。在中度UC患者和健康对照者中各随机选取8例,以ELISA、real-time PCR和蛋白质印迹法检测TAM受体的血清水平及其在肠黏膜组织中的表达,以Pearson相关系数分析血清Tyro3水平与UC常用临床指标的相关性。进一步以免疫组化法检测所有研究对象的TAM受体在肠黏膜组织中的表达水平。结果:Axl和Mertk在UC患者血清和肠黏膜中的表达不完全一致。中度UC组血清Tyro3水平以及肠黏膜Tyro3 mRNA和蛋白表达均较健康对照组显著升高(P均<0.05);血清Tyro3水平与血小板计数、C反应蛋白呈显著正相关,与白蛋白呈显著负相关(r=0.97,r=0.96,r=-0.86,P均<0.05)。肠黏膜Tyro3阳性细胞率与UC疾病严重程度呈正相关(P均<0.05)。结论:Tyro3与UC密切相关,且与疾病严重程度呈正相关,有望成为UC的新型分子标志物和治疗靶点。TAM receptors(Tyro3,Axl and Mertk),as subfamily of receptor tyrosine kinases,are intracellular negative feedback regulators and play a crucial role in regulating inflammation and immune response.Aims:To study the expressions and clinical value of TAM receptors in serum and intestinal mucosa of patients with ulcerative colitis(UC).Methods:Forty⁃five patients who were initially diagnosed as active UC from June,2020 to May,2021 at the First Affiliated Hospital of Kunming Medical University were enrolled prospectively.Fifteen healthy subjects were served as the control group.Eight cases each in moderate UC group and healthy control group were selected randomly for detection of TAM receptors in serum and intestinal mucosa by ELISA,real⁃time PCR and Western blotting.The correlations of serum Tyro3 with routine clinical indicators of UC were analyzed by Pearson correlation coefficient.Furthermore,immunohistochemistry was used to detect the expression level of TAM receptors in intestinal mucosa in all UC patients and the healthy controls.Results:Expressions of Axl and Mertk were not fully consistent in serum and intestinal mucosa in UC patients.While the serum Tyro3 level,as well as the intestinal Tyro3 mRNA and protein expressions were consistently increased in moderate UC patients than in controls(all P<0.05).Serum level of Tyro3 was positively correlated with platelet count and C⁃reactive protein,and negatively correlated with albumin in moderate UC patients(r=0.97,r=0.96,r=-0.86,all P<0.05).Positivity rate of Tyro3 in intestinal mucosa of UC patients was positively correlated with the disease severity(all P<0.05).Conclusions:Tyro3 is closely related to UC and positively correlated with the disease severity.It might be a promising novel molecular marker and therapeutic target of UC.

关 键 词：结肠炎 溃疡性 TAM受体酪氨酸激酶 Tyro3 AXL Mertk 

分 类 号：R574.62[医药卫生—消化系统]