摘要
探讨细胞程序性死亡配体-1(programmed cell death-ligand 1,PD-L1)在溃疡性结肠炎(ulcerative colitis,UC)发病机制中的作用。方法 收集2022年1-9月于陆军军医大学第一附属医院消化内科肠镜室就诊的18~64岁的UC患者结肠组织标本29例,同期收集非UC患者结肠组织标本22例,采用免疫组化和RT-qPCR检测PD-L1和炎症因子IL-1β、IL-6、IL-17a、IL-22、TGF-β1的表达。选取8~10周龄C57BL/6雄性小鼠24只(23~26 g),分为空白对照组(n=4)、PD-L1-Fc组(n=4)、葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)组(n=8)、DSS+PD-L1-Fc组(n=8),DSS组及DSS+PD-L1-Fc组连续7天予以2.5%DSS溶液自由饮水,第8天更换为正常饮水,其余组正常饮水,第3天予以PD-L1-Fc组及DSS+PD-L1-Fc组小鼠腹腔注射PD-L1-Fc蛋白(1 mg/mL)40μg/只,造模后8~10天检测各组小鼠结肠黏膜中PD-L1的表达情况,并观察各组小鼠的体质量、粪便性状、活体结肠黏膜形态变化、组织病理学改变及炎症因子改变情况。结果 与对照组相比,UC患者结肠黏膜中PD-L1表达显著升高(43.03±4.044,P<0.001),促炎因子IL-1β、IL-6及抗炎因子IL-22、TGF-β1的表达均升高(P<0.05);在DSS小鼠模型中同样存在这一现象。腹腔注射PD-L1-Fc蛋白后,DSS小鼠的体质量、粪便评分、结肠黏膜大体形态及显微镜下炎症程度明显改善(P<0.05),IL-6、IL-17a下调(P<0.05),IL-22、Foxp3上调(P<0.05)。结论 PD-L1在UC患者及小鼠DSS结肠炎模型中升高,可能是机体的一种适应性保护作用。
Objective To explore the role of programmed cell death-ligand 1(PD-L1) in pathogenesis of ulcerative colitis(UC).Methods A total of 29 colon tissue samples from UC patients aged 18~64 years who underwent the colonoscopy in our department from January 2022 to September 2022 were collected,and another 22 colon tissue samples from non-UC patients were also collected during the same period.The expression of PD-L1 and inflammatory factors IL-1β,IL-6,IL-17a,IL-22 and TGF-β1 were detected by immunohistochemistry and RT-qPCR.Twenty-four male C57BL/6 mice(8~10 weeks old,23~26 g) were randomly divided into blank control group(n=4),PD-L1-Fc group(n=4),dextran sulfate sodium salt(DSS) group(n=8),and DSS+PD-L1-Fc group(n=8).The mice from the DSS group and DSS+PD-L1-Fc group were given 2.5%DSS solution for 7 consecutive days,and were changed to normal drinking water on the 8th day.The animals of the other groups were given normal drinking water.On the 3rd day,the mice in the PD-L1-Fc group and DSS+PD-L1-Fc group were injected intraperitoneally with PD-L1-Fc protein(1 mg/mL,40 μg/animal).In 8~10 d after modeling,the expression of PD-L1 in colonic mucosa was detected,and the body weight,fecal traits,morphological changes,histopathological changes and inflammatory factors were observed in different groups.Results The expression of PD-L1 was significantly increased in the colonic mucosa of UC patients(43.03±4.044,P<0.001) than of normal colon tissue samples,and the expression of pro-inflammatory factors IL-1β and IL-6 and anti-inflammatory factors IL-22 and TGF-β1 were increased(P<0.05),which also existed in DSS mouse models.Intraperitoneal injection of PD-L1-Fc protein improved body weight,fecal score,gross morphology of colonic mucosa and microscopic inflammation(P<0.05),down-regulated IL-6 and IL-17a(P<0.05) and up-regulated IL-22 and Foxp3(P<0.05) in the DSS+PD-L1-Fc mice when compared with the DSS group.Conclusion The upregulation of PD-L1 in UC patients and DSS-induced colitis mouse models may play an adaptive protective role.
作者
宋娅岚
吴天宇
陈聪
武振宇
汤旭东
陈磊
SONG Yalan;WU Tianyu;CHEN Cong;WU Zhenyu;TANG Xudong;CHEN Lei(Department of Gastroenterology,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400038,China)
出处
《陆军军医大学学报》
CAS
CSCD
北大核心
2023年第2期155-164,共10页
Journal of Army Medical University
基金
国家自然基金面上项目(81470850)。
