乙酰肝素酶在溃疡性结肠炎肠黏膜中的表达及在致病机制中的作用

Expression of heparanase in colonic mucosa of ulcerative colitis and its role in pathogenesis

目的 探讨乙酰肝素酶(heparanase,HPSE)在溃疡性结肠炎(ulcerative colitis,UC)患者肠黏膜中表达的改变,及其表达是否与不同临床分期和不同炎症程度相关。同时也讨论了 HPSE表达在UC致病机制中的作用。方法 正常对照组为13名健康成人,确诊的 28 例 UC患者中 25 例根据病情分为活动期11例、缓解期14例,并对 24 例的病理组织学炎症进行分级,Ⅲ、Ⅳ级 10 例,Ⅰ、Ⅱ级 14例。分别采用RT-PCR和Western印迹法对不同分组的HPSE表达水平进行检测。结果 HPSE在正常对照组肠黏膜中无表达,在缓解期和病理分级Ⅰ、Ⅱ级的肠黏膜中均呈现低表达,而在活动期和病理分级Ⅲ、Ⅳ级的肠黏膜中表达显著升高。结论 HPSE在UC肠黏膜中呈阳性表达,且其表达水平与病情轻重和炎症严重程度呈正相关,它可能在UC肠黏膜上皮重塑和疾病的发生和发展中起重要作用,而HPSE抑制剂则有可能用于UC的治疗。

Objective To investigate the alteration of heparanase expression in colonic mucosa of patients with ulcerative colitis (UC) and their correlation with clinical staging and the degree of inflammation in the colonic mucosa, and the possible roles of heparanase expression in the pathogenesis of UC. Methods Thirteen healthy adult volunteers were selected as normal control. Twenty-five of 28 patients with endoscopically and histologically confirmed UC were divided into active group (11 cases) and inactive group (14 cases) based on clinical activity index and inflammation index. Among them 24 patients were also classified histologically as inflammation grade Ⅲ, Ⅳ(10 cases) and inflammation grade Ⅰ, Ⅱ(14 cases). The expression of heparanase was determined by RT-PCR and Western blot. Results Heparanase was not detected in colonic mucosa of healthy controls. Meanwhile, active UC had much higher heparanase mRNA expression compared to inactive UC, and patients with inflammation grade Ⅲ, Ⅳ also exhibited higher expression of heparanase protein than those with inflammation grade Ⅰ, Ⅱ. Conclusions Heparanase was expressed in colonic mucosa in patients with UC, and the intensity of heparanase (expressions) was positively related with the degrees of inflammation and the activity of (disease). Therefore heparanase may directly contribute to the acute inflammation of colon mucosa and (mucosal) remodeling in UC.