糖蛋白非转移性黑色素瘤B在小鼠慢性肠道纤维化中的表达及意义  

Expression and significance of glycoprotein nonmetastatic melanoma protein B in mice with chronic intestinal fibrosis

作　　者：鲍淑梅 李卉[1] 张亚杰[1] 周林妍[1] 解莹[1] 田丰[1] Bao Shumei;Li Hui;Zhang Yajie;Zhou Linyan;Xie Ying;Tian Feng(Department of Gastroenterology,Shengjing Hospital,China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院消化内科,沈阳110004

出　　处：《中华炎性肠病杂志（中英文）》2022年第4期335-340,共6页Chinese Journal of Inflammatory Bowel Diseases

基　　金：辽宁省高等学校基本科研项目(LFWK201707);辽宁省博士启动基金(2021-BS-114)。

摘　　要：目的探讨糖蛋白非转移性黑色素瘤B(Gpnmb)在小鼠慢性肠道纤维化中的作用。方法12只BALB/c小鼠随机平均分为模型组和对照组,模型组给予含2.5%葡聚糖硫酸钠(DSS)的饮用水建立慢性肠道纤维化模型,对照组不做处理。计算小鼠的体质量、结肠长度、结肠组织形态学评分和组织学损伤评分。采用HE染色评估结肠炎症程度,Masson染色评估结肠纤维化程度,免疫组织化学法和Western blot测定结肠组织中Ⅰ型胶原蛋白α2(Col1α2)、Gpnmb及其受体CD44蛋白表达水平,荧光定量PCR检测Col1α2和Gpnmb mRNA表达水平。采用t检验比较两组上述指标的差异。结果与对照组相比,模型组小鼠的结肠更短,结肠组织形态学评分更高,差异均具有统计学意义(均P<0.05)。HE染色显示,模型组结肠黏膜中肠腺排列紊乱,萎缩减少,杯状细胞减少,黏膜和黏膜下层可见水肿,中性粒细胞和淋巴细胞浸润;对照组黏膜正常,无炎症发生。与对照组相比,模型组小鼠结肠的组织学损伤评分更高,纤维化面积更大,Col1α2、Gpnmb、CD44蛋白的表达更高,Col1α2和Gpnmb mRNA的表达更高,差异均具有统计学意义(均P<0.05)。结论Gpnmb可能通过CD44促进DSS诱导的小鼠慢性肠道纤维化的发生发展。Objective To explore the role of glycoprotein nonmetastatic melanoma protein B(Gpnmb)in chronic intestinal fibrosis of mice induced by dextran sodium sulfate(DSS).Methods Twelve BALB/c mice were randomly and equally divided into model group and control group.The mice in model group received water containing 2.5%dextran sodium sulfate(DSS)to establish a chronic intestinal fibrosis model,while the mice in control group were not treated.The body mass,colon length,colonic histomorphology score and histological damage score of mice were calculated.The inflammatory degree of colitis was assessed by HE staining and the degree of colonic fibrosis was assessed by Masson staining.The protein expression of collagen typeⅠalpha 2(Col1α2),Gpnmb and its receptor CD44 in colonic tissues was determined by immunohistochemistry and Western blot.The mRNA expression of Col1α2 and Gpnmb was detected by fluorescent quantitative PCR.The differences of the above indexes between the two groups were compared by t test.Results Compared with the control group,the colon length of the model group was shorter and the colonic histomorphology score was higher(all P<0.05).HE staining results showed that the intestinal glands in the colonic mucosa were disorderly arranged,atrophic and reduced,the goblet cells were less,and edema,neutrophil and lymphocyte infiltration were seen in the mucosa and submucosa in the model group.The mucosa of the control group was normal without inflammation.Compared with the control group,the histological damage score of the colon in the model group was higher and the fibrotic area was larger,the protein expression of Col1α2,Gpnmb and CD44 was higher,the mRNA expression of Col1α2 and Gpnmb were higher(all P<0.05).Conclusion Gpnmb may promote the occurrence and development of DSS-induced chronic intestinal fibrosis in mice through CD44.

关 键 词：炎症性肠病 糖蛋白非转移性黑色素瘤B 葡聚糖硫酸钠 肠纤维化 小鼠 

分 类 号：R735.3[医药卫生—肿瘤]