摘要
目的 探讨载5-氨基水杨酸(5-ASA)的尤特奇S100包衣氧化铁-壳聚糖纳米复合物(ES-IOCS/5-ASA)对溃疡性结肠炎小鼠的治疗作用及机制。方法 将6~8周龄雄性C57BL/6J小鼠随机分为正常对照组、三硝基苯磺酸(TNBS)模型组、5-ASA组和ES-IOCS/5-ASA组。通过TNBS建立小鼠溃疡性结肠炎模型。5-ASA组和ES-IOCS/5-ASA组于TNBS造模后进行灌胃给药,连续灌胃7 d。7 d后处死小鼠,评估小鼠疾病活动指数(DAI),酶联免疫吸附法(ELISA)检测小鼠血清白细胞介素-1β(IL-1β)、IL-6和肿瘤坏死因子-α(TNF-α)水平,取小鼠肠道组织进行苏木精和伊红(HE)染色,Western blot法检测肠道组织含NLR家族Pyrin域蛋白3(NLRP3)炎症小体相关蛋白NLRP3、凋亡相关斑点(ASC)和IL-1β的表达水平。结果 与正常对照组相比,TNBS模型组小鼠体质量明显下降(P<0.001),DAI评分显著升高(P<0.001),结肠长度明显缩短(P<0.001),结肠组织病理学评分明显增加(P<0.001),血清炎症因子表达显著升高(P<0.05),NLRP3炎症小体相关蛋白表达明显上调(P<0.001)。与TNBS模型组相比,ES-IOCS/5-ASA组小鼠DAI评分显著降低(P<0.001),肠道缩短被抑制(P<0.001),结肠组织病理学评分明显下降(P<0.001),血清炎症因子IL-1β、TNF-α的表达降低(P<0.05),但两组间血清IL-6水平差异无统计学意义(P>0.05),NLRP3炎症小体相关蛋白的表达显著下调(P<0.001)。5-ASA对小鼠肠道炎症无明显缓解作用。结论 ES-IOCS/5-ASA可能通过抑制NLRP3炎症小体来改善TNBS诱导的小鼠溃疡性结肠炎症状。
Objective To investigate the effect and its underlying mechanism of Eudragit S100 coated iron oxide-chitosan nanocom-posites of 5-aminosalicylic acid on ulcerative colitis in mice.Methods Six to eight weeks old male C57BL/6 mice were randomly assigned to four groups:normal control group,TNBS model group,5-ASA group and ES-IOCS/5-ASA group.The mouse ulcerative colitis model was established by TNBS.The mice in 5-ASA group and ES-IOCS/5-ASA group were gavaged with the corresponding drugs for seven consecutive days after modeling.Then the mice were killed.The disease activity index(DAI)was evaluated,the serum levels of IL-1β,IL-6 and TNF-αwere detected by ELISA,and the colon tissues of mice were stained with hematoxylin and eosin(HE).Western blot was used to determine the protein levels of NLRP3,apoptosis-associated speck-like protein(ASC),and IL-1βin colon tissues.Results Compared with normal control group,the body weight was significantly decreased in TNBS model group(P<0.001),the disease activity index(DAI)was significantly increased(P<0.001),the colon length was shortened(P<0.001),the patho-logical injury score was increased(P<0.001),the levels of IL-1β,IL-6 and TNF-αin serum were significantly increased(P<0.05),and the expressions of NLRP3,ASC,and IL-1βwere upregulated(P<0.001).Compared with TNBS model group,the DAI score was reduced in ES-IOCS/5-ASA group(P<0.001),the colon length was enlarged(P<0.001),DAI was decreased(P<0.001),the expres-sions of pro-inflammatory cytokines IL-1β,TNF-αin serum were downregulated(P<0.05),and the expression of NLRP3 inflamma-some in colon tissues was decreased(P<0.001).However,5-ASA had poor efficacy on ulcerative colitis in mice.Conclusion ES-IOCS/5-ASA may alleviate TNBS-induced ulcerative colitis in mice through the inhibition of NLRP3 inflammasome activation.
作者
张丹丹
王燕
赵冉
谭学明
ZHANG Dandan;WANG Yan;ZHAO Ran;TAN Xueming(Department of Gastroenterology,Zhongda Hospital Southeast University(Jiangbei),Nanjing 210048,China)
出处
《山西医科大学学报》
2025年第2期151-157,共7页
Journal of Shanxi Medical University
基金
东南大学附属中大医院江北院区面上项目(JB202005M)。
作者简介
张丹丹,女,1988-02生,硕士,主治医师,E-mail:dandanz8088@163.com。
