实验性血小板微粒对葡聚糖硫酸钠结肠炎小鼠肠黏膜通透性的影响  

ffects of platelet microparticles on intestinal mucosal permeability in mice with DSS colitis

作　　者：杨彬 李会会 张路遥 刘秋圆 王迪迪 胡静[1] 韩玮[1] 刘晓昌[1] 梅俏[1] Yang Bin;Li Huihui;Zhang Luyao;Liu Qiuyuan;Wang Didi;Hu Jing;Han Wei;Liu Xiaochang;Mei Qiao(Dept of Gastroenterology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院消化内科,合肥230022

出　　处：《安徽医科大学学报》2023年第8期1361-1366,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82170564)。

摘　　要：目的探讨血小板微粒(PMPs)对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠肠道炎症程度及肠黏膜通透性的影响。方法实验分为正常对照组(n=10,饮用无菌蒸馏水+腹腔注射0.9%氯化钠溶液)、PMPs组(n=10,饮用无菌蒸馏水+腹腔注射PMPs)、DSS模型组(n=10,饮用DSS溶液+腹腔注射0.9%氯化钠溶液)、实验组(n=15,饮用DSS溶液+腹腔注射PMPs)。收集炎症性肠病(IBD)患者外周血制备PMPs悬液。小鼠自由饮用5%DSS溶液1周构建结肠炎模型,连续7 d腹腔注射PMPs,每天记录疾病活动指数(DAI)评分,实验结束后取结肠标本,HE染色计算小鼠病理组织学评分(HI)评估肠道炎症的严重程度,结肠匀浆检测髓过氧化物酶(MPO)、中性粒细胞弹性蛋白酶(NE)、组蛋白H3(citH3)及游离DNA水平,透射电镜观察肠黏膜结构,采用异硫氰酸荧光素-葡聚糖(FITC-D)法检测肠黏膜通透性。结果与正常对照组相比,PMPs组小鼠结肠黏膜水肿、上皮结构破坏严重、炎细胞广泛聚集,总体HI升高(P<0.01);PMPs组小鼠结肠组织匀浆IL-1β、TNF-α等炎症因子水平升高(P<0.05),NETs表达增加(P<0.05);PMPs组小鼠血浆FITC-D水平明显增高(P<0.05),肠黏膜通透性增加。与DSS组相比,实验组小鼠血浆FITC-D水平更高(P<0.05)、电镜下结肠上皮损伤更重。结论PMPs可在小鼠体内诱导NETs形成,促进小鼠结肠炎症的产生,增加DSS结肠炎小鼠的肠黏膜通透性,加重肠道炎症。Objective To investigate the effect of platelet particles on the extent of intestinal inflammation and intestinal mucosal permeability in mice with dextran sodium sulfate induced colitis.Methods The experiment was divided into four groups:normal control group(n=10,drinking sterile distilled water+intraperitoneal injection of 0.9%sodium chloride solution),PMPs group(n=10,drinking sterile distilled water+intraperitoneal injection of PMPs),DSS model group(n=10,drinking DSS solution+intraperitoneal injection of 0.9%sodium chloride solution),and experimental group(n=15,drinking DSS solution+intraperitoneal injection of PMPs).Peripheral blood-derived PMPs suspension was collected from inflammatory bowel disease(IBD)patients.A colitis model was constructed in mice by allowing them to freely drink a 5%DSS solution for 1 week,followed by continuous intraperitoneal injection of PMPs for 7 days.Disease activity index(DAI)scores was recorded daily and the severity of intestinal inflammation with histopathological scores(HI)was assessed by HE staining of colon samples at the end of the experiment.Myeloperoxidase(MPO),neutrophil elastase(NE),citrullinated histone H3(citH3),and free DNA levels were measured in colon homogenate,observe intestinal mucosal structure by transmission electron microscopy,and intestinal permeability was tested using fluorescein isothiocyanate-dextran(FITC-D).Results Compared with the normal control group,the colonic mucosa of mice in the PMPs group showed edema,severe destruction of epithelial structure,extensive aggregation of inflammatory cells,and increased overall HI score(P<0.01);the levels of inflammatory factors such as IL-1β and TNF-α in colonic tissue homogenates of mice in the PMPs group increased(P<0.05),and the expression of NETs increased(P<0.05);the plasma FITC-D level of mice in the PMPs group significantly increased(P<0.05),and the permeability of intestinal mucosa increased.Compared with the DSS group,the experimental group mice had higher plasma FITC-D levels(P<0.05)and more electr

关 键 词：炎症性肠病 血小板微粒 中性粒细胞胞外诱捕网 结肠炎 肠黏膜通透性 

分 类 号：R573.9[医药卫生—消化系统]