乌司他丁对脓毒症晚期大鼠肠黏膜屏障功能的影响  

Effect of Ulinastatin on barrier function of intestinal mucosa of rats with advanced sepsis

作　　者：张萌[1] 曾志芬[1] 梁淑敏 杨世亮 周天恩 ZHANG Meng;ZENG Zhi-fen;LIANG Shu-min;YANG Shi-liang;ZHOU Tian-en(Sun Yat-sen Memorial Hospital,Guangzhou,Guangdong 510289,China;不详)

机构地区：[1]中山大学孙逸仙纪念医院全科医学科,广东广州510289 [2]佛山市第一人民医院急诊科,广东佛山528000

出　　处：《中华医院感染学杂志》2022年第5期679-683,共5页Chinese Journal of Nosocomiology

基　　金：广东省医学科学基金资助项目(A2020307)。

摘　　要：目的 探讨乌司他丁对脓毒症晚期大鼠肠黏膜屏障功能的影响。方法 选取18只SD雄性大鼠随机分为假手术组、脓毒症组和治疗组,每组6只。盲肠结扎穿孔术(CLP)建立脓毒症模型。假手术组切开腹壁后缝合,其余两组行CLP术。治疗组在建模后20 min经尾静脉注射乌司他丁,其余两组于相同时间点注射等容积生理盐水。各组大鼠于CLP后24 h处以安乐死。取心脏血、股动脉血及小肠标本。分别检测小肠病理光镜、空肠组织紧密连接蛋白(ZO-1)、血浆二胺氧化酶(DAO)、小肠微管相关蛋白质轻链3(LC3)和降解底物P62。结果 脓毒症组大鼠小肠绒毛顶端上皮脱落,固有层崩解,毛细血管出血和溃疡形成,乌司他丁治疗组显著减轻了上述病理改变;与假手术组相比,脓毒症组ZO-1水平降低(P<0.05),乌司他丁治疗组可提升其水平(P<0.05);与假手术组相比,脓毒症组DAO浓度升高(P<0.05),乌司他丁治疗组可降低其浓度(P<0.05);与假手术组相比,脓毒症组P62表达增加,LC3Ⅱ/LC3Ⅰ下降(P<0.05);与脓毒症组比较,乌司他丁治疗组p62表达下降,LC3Ⅱ/LC3Ⅰ上升(P<0.05)。结论 脓毒症晚期大鼠的肠上皮自噬功能受损;乌司他丁可通过提升其水平改善脓毒症大鼠肠黏膜屏障功能障碍。OBJECTIVE To explore the effect of Ulinastatin in barrier function of intestinal mucosa of rats with advanced sepsis. METHODS Totally 18 SD male rats were randomly divided into the sham surgery group, the sepsis group and the treatment group, with 6 rats in each group. Cecal ligation and puncture(CLP) method was used to establish sepsis model. The abdominal wall was cut and sutured without CLP in the sham surgery group, and the CLP was conducted in other 2 groups. The treatment group was treated with tail vein injection of Ulinastatin after modeling for 20 min, the rest of two groups were treated with injection of same volume of normal saline at the same time points. All of the rats were euthanized 24 hours after CLP. The heart blood, femoral artery blood and small intestine specimens were collected. The pathological light microscopy of small intestine, expression of tight junction protein(ZO-1), plasma diamine oxidase(DAO), intestinal microtubule associated protein light chain 3(LC3) and degradation substrate P62 were detected. RESULTS In the sepsis group, the epithelium on the top of intestinal villi fell off, lamina propria disintegrated, capillary hemorrhage and ulcer formed. The above pathological changes were significantly alleviated in the treatment group. As compared with the sham surgery group, the ZO-1 level of the sepsis group was reduced significantly(P<0.05), the ZO-1 level of the treatment group was elevated significantly(P<0.05). As compared with the sham surgery group, the DAO concentration of the sepsis group was elevated significantly(P<0.05), the DAO concentration of the treatment group was reduced significantly(P<0.05). As compared with the sham surgery group, the expression level of P62 of the sepsis group was increased significantly, and the expression level of LC3Ⅱ/LC3Ⅰ was reduced(P<0.05);as compared with the sepsis group, the expression level of p62 of the treatment group was reduced significantly, while the expression level of LC3Ⅱ/LC3Ⅰ was elevated significantly(P<0.05). CONCLUS

关 键 词：脓毒症晚期 肠上皮细胞 乌司他丁 自噬 肠黏膜屏障功能 大鼠 

分 类 号：R631[医药卫生—外科学]