静注人免疫球蛋白对溃疡性结肠炎的治疗作用  

Therapeutic efficacy of intravenous immunoglobulin in ulcerative colitis

作　　者：龙茜 王宗奎[1] 李长清[1] 张容[1] LONG Qian;WANG Zongkui;LI Changqing;ZHANG Rong(Institute of Blood Transfusion,Chinese Academy of Medical Sciences&Peking Union Medical College,Chengdu 610052,China)

机构地区：[1]中国医学科学院北京协和医学院输血研究所,四川成都610052

出　　处：《中国输血杂志》2025年第4期522-530,共9页Chinese Journal of Blood Transfusion

基　　金：中国医学科学院医学与健康科技创新工程重大协同创新项目(2021-I2M-1-060);四川省自然科学基金面上项目(2023NSFSC0714)。

摘　　要：目的探讨静注人免疫球蛋白(intravenous immunoglobuin,IVIG)对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的溃疡性结肠炎(UC)小鼠模型的治疗作用。方法将C57BL/6小鼠随机分为Control组(对照组)、DSS组(模型组)及DSS+IVIG组(治疗组)。DSS组和DSS+IVIG组采用小鼠自由饮用含3%DSS的饮用水建立DSS结肠炎模型。在建模过程中,DSS+IVIG组给予IVIG尾静脉注射给药(1 g/kg/2d),DSS组给予生理盐水尾静脉注射给药(1 g/kg/2d)。每天观察小鼠症状、记录体重并计算疾病活动指数(disease activity index,DAI)。实验结束后,HE(苏木精-伊红)染色观察结肠组织病理学变化及炎性细胞浸润,PAS(过碘酸雪夫)染色定量杯状细胞数量。Luminex法检测血清中TNF-α、IL-6和MMPs等炎性相关因子水平;western blot和qRT-PCR分别检测紧密连接蛋白(ZO-1、Occludin、Claudin-3)的蛋白表达及mRNA水平。结果DSS诱导小鼠体重减轻、腹泻、便血、DAI评分增加、结肠长度缩短。与DSS组相比,加入IVIG之后小鼠DAI评分显著降低(P<0.001),结肠长度增加(P<0.001)、黏膜炎性细胞浸润及病理损伤减少(P<0.001)、杯状细胞数量增加(P<0.05),炎性相关因子TNF-α、IL-6、IL-6R、MMP2、MMP3和Chitinase3like1水平(均P<0.05)降低。Western blot及qRT-PCR结果显示,IVIG显著上调ZO-1、Occludin和Claudin-3的蛋白表达及ZO-1和Occludin的mRNA水平(均P<0.05)。结论IVIG可通过抑制TNF-α、IL-6和MMPs等炎性相关因子的病理性释放,及恢复肠道屏障的完整性,对结肠炎产生保护效应。Objective To explore the therapeutic effects of intravenous immunoglobulin(IVIG)on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC).Methods C57BL/6 mice were randomly assigned to the control group,the DSS group(model)and the DSS+IVIG group(treatment).The DSS group and the DSS+IVIG group received 3%DSS in drinking water to establish the acute UC mouse model.During the experiment,the DSS+IVIG group received IVIG(1 g/kg/2d)via tail vein injection,while the DSS group received equivalent saline via tail vein injection at the same dose and frequency.The symptoms of the mice were observed,body weight changes were recorded,and the disease activity index(DAI)was calculated daily.At the end of the experiment,hematoxylin-eosin(HE)staining was used to observe the pathological changes and inflammatory cell infiltration of colon tissue;Periodic acid-Schiff(PAS)staining was used to quantify the number of goblet cells;Luminex was used to detect the levels of inflammatory-related cytokines(such as TNF-α,IL-6 and MMPs)in colon;western blot and qRT-PCR were respectively used to detect the protein expression and mRNA levels of tight junction proteins(ZO-1,Occludin,Claudin-3).Results DSS induced weight loss,diarrhea,bloody stool,increased DAI score,and shortened colon length in mice.Compared with DSS group,after the administration of IVIG,the DAI score was significantly reduced(P<0.001),colon length was increased(P<0.001),infiltration of inflammatory cells and pathological damage were alleviated in colonic mucosa(P<0.001),the number of goblet cells were increased(P<0.05),and the levels of inflammatory-related cytokines TNF-α,IL-6,IL-6R,MMP2,MMP3 and Chitinase3like1 were decreased(all P<0.05).Western blot and qRT-PCR results showed that IVIG significantly up-regulated the protein expression of ZO-1,Occludin and claudin-3(all P<0.05)and the mRNA levels of ZO-1 and Occludin(all P<0.05).Conclusion IVIG has protective effects on colitis by inhibiting the pathological release of inflammatory-related cytokines such as TNF-α,IL-

关 键 词：IVIG 溃疡性结肠炎 肠道炎症 肠道屏障 紧密连接蛋白 

分 类 号：R457.2[医药卫生—治疗学] R574.62[医药卫生—临床医学]