【摘要】 [目的]观察肠黏膜屏障损伤与溃疡性结肠炎(UC)的关系、糜蛋白酶联合锡类散保留灌肠疗法的临床疗效,探讨其对UC患者肠黏膜屏障的影响及作用机制。[方法]收集2013年1月～2017年6月在我院确诊为溃疡性结肠炎的158例患者,根据治疗方案不同随机分为治疗组和对照组,并选取20例在我院行肠镜检查的健康体检者的资料做参照。对照组给予美沙拉嗪肠溶片口服、保留灌肠,灌肠液为生理盐水,同时加入庆大霉素、氟美松,治疗组在对照组基础上加用糜蛋白酶、锡类散保留灌肠。2组患者根据Mayo评分,分为轻、中、重度3个亚组。以咬合蛋白(Occludin)和紧密连接蛋白1(Claudin-1)、血清β-防御素(β-defensin)和分泌型免疫球蛋白A(secretory immunoglobulin A,sIgA)分别代表肠道机械屏障、化学屏障、和免疫屏障,免疫组化法检测3种蛋白表达,并与相关临床指标进行统计学分析。[结果]与健康人群比较,UC患者Occludin、Claudin-1表达水平显著降低(P<0.05),血清β-defensin表达显著增加,sIgA表达显著减少,差异均有统计学意义(P<0.05)。2组UC患者综合分析:轻、中、重度亚组间肠黏膜Occludin、Claudin-1表达组间差异有统计学意义(P<0.05),随着UC分级增加表达明显减少,(r=-0.890,-0.888);轻、中、重度UC患者肠黏膜β-defensin表达组间差异有统计学意义(P<0.05),随着UC分级增加表达明显增多(r=0.596);sIgA在不同分级UC肠黏膜表达差异无统计学意义。治疗后2组患者症状均有改善,治疗组较对照组患者Mayo评分下降更为显著,差异有统计学意义;治疗后Occludin、Claudin-1表达上升,血清β-defensin表达下降,sIgA表达上升,治疗组较对照组更为明显,差异均有统计学意义(P<0.05)。[结论]UC患者肠黏膜屏障出现损伤,其中机械屏障、化学屏障与疾病的分级具有相关性;糜蛋白酶联合锡类散保留灌肠对UC患者的肠黏膜屏障有明显的保护作用,可显著提高临床效果。更多还原

【Abstract】 [Objective] To observe the relationship between intestinal mucosal barrier injury and ulcerative colitis(UC), and the clinical efficacy of chymotrypsin combined with Xileisan retention enema therapy, and to explore the effect on the intestinal mucosal barrier in UC patients and mechanism. [Methods]A total of 158 patients with ulcerative colitis diagnosed in our hospital from 2013.1 to 2017.6 were randomly divided into treatment group and control group according to different treatment schemes. Besides the data of 20 healthy people undergoing colonoscopy in our hospital were compared. Patients in control group were treated with mesalazine enteric-coated tablets orally and retention enema, meanwhile gentamicin and flumethasone were added into the enema solution. And patients in the treatment group were treated with chymotrypsin and Xileisan retention enema therapy based on treatment of the control group. According to the Mayo score, the two groups were divided into 3 subgroups: mild, moderate and severe groups. The clinical efficacy of each group was observed before and after treatment.Immunohistochemistrywas performed to examine the expression of Occludin and Claudin-1, β-defensin, sIgA, which respectively reflect the changes of mechanical barrier, chemical barrier and immune barrier in intestinal mucosa. The result and the clinical data were analyzed.[Results]Compared with healthy people, the expressionlevels of Occludin, Claudin-1 and sIgA in UC patients decreased significantly, while the expression of β-defensin increased significantly(P<0.05). There was a significant difference in Occludin and Claudin-1 levels among different active subgroups in UC patients(P<0.05),and the levels decreased significantly with the increase of UC classification(r=-0.890,-0.888). β-defensin levels were significant differently among different active subgroups(P<0.05),and the levels increased significantly with the increase of UC classification(r=0.596). There was no significant difference in the sIgA levels among the three stages. There was no significant difference in the sIgA levels among the three stages.Compared with before treatment the symptoms of the two groups were alleviated, and the treatment group had a more significant decrease in the Mayo score than the control group, and the difference was statistically significant. After treatment, the expression of Occludin Claudin-1 and sIgAincreased, while the expression of β-defensin decreased, and the changes of the thetreatment group were more obvious than that of the control group(P<0.05).[Conclusion]The intestinal mucosal barrier was damaged in UC patients, and the mechanical barrier and chemical barrier were correlated with UC grading. The retention enema therapy of chymotrypsin combined with xileisanhas obvious effect to protect the intestinal mucosal barrier in UC patients, which significantly improve the clinical effect.更多还原