摘要
目的探讨白藜芦醇(resveratrol,RSV)对坏死性小肠结肠炎(NEC)小鼠细胞焦亡的影响及其调控机制。方法选取5日龄C57BL/6新生小鼠,分为对照组(Control)、NEC模型组以及RSV治疗组(RSV)。Control组小鼠给予正常母乳喂养;NEC组小鼠给予缺氧刺激,人工喂养并伴有脂多糖干预处理;RSV治疗组小鼠给予RSV灌胃(0.1 mg·kg^(-1)·d^(-1))。以上各组在出生后12 d后收集各组新生小鼠末端回肠组织,HE染色观察病理学形态,RT-PCR检测miR-223水平,Western blot检测caspase-1、GSDMD、IL-1β和IL-18表达;ELISA检测IL-1β和IL-18含量。结果与Control组相比,NEC组新生小鼠肠道出现明显的损伤,miR-223表达下调(P<0.01),cleaved-caspase-1、GSDMD-N、IL-1β和IL-18表达上调(P<0.01),IL-1β和IL-18含量增加(P<0.01)。与NEC组相比,RSV组新生小鼠肠道组织损伤程度减轻,miR-223表达上调(P<0.01),cleaved-caspase-1、GSDMD-N、IL-1β和IL-18表达下调(P<0.05或P<0.01),IL-1β和IL-18含量降低(P<0.01)。结论RSV能够通过上调miR-223,抑制细胞焦亡,缓解NEC肠道损伤。
Aim To explore the effect of resveratrol(RSV)on necrotizing enterocolitis(NEC)mouse pyroptosis and its regulatory mechanism.Methods Five-day-old C57BL/6 newborn mice were selected and divided into control group(Control),NEC model group,and RSV treatment group(RSV).The mice in the control group were given normal breastfeeding,while those in the NEC group were given hypoxia stimulation and artificial feeding accompanied by lipopolysaccharide intervention,and the mice in the RSV treatment group were given RSV gavage(1 mg·kg^(-1)),once a day.In the above groups the terminal ileum tissues of newborn mice in each group were collected 12 days after birth.HE staining was used to observe the pathological morphology,RT-PCR was used to detect the level of miR-223 in the ileum,Western blot was employed to detect the expression of caspase-1,GSDMD,IL-1βand IL-18,and ELISA was used to assess the content of IL-1βand IL-18.Results Compared with the control group,the neonatal mice in the NEC group showed obvious damage to the intestine,the expression of miR-223 was down-regulated(P<0.01),the expression of cleaved-caspase-1,GSDMD-N,IL-1βand IL-18 was up-regulated(P<0.01),and the content of serum IL-1βand IL-18 increased(P<0.01).Compared with the NEC group,the intestinal tissue damage of the newborn mice in the RSV group was reduced,the expression of miR-223 was up-regulated(P<0.01),cleaved-caspase-1,GSDMD-N,IL-1βand IL-18 was down-regulated(P<0.05 or P<0.01),and the levels of serum IL-1βand IL-18 decreased(P<0.01).Conclusions RSV can up-regulate miR-223,inhibit pyroptosis,and alleviate NEC intestinal injury.
作者
王瑛
张莹楠
常新捷
张英剑
WANG Ying;ZHANG Ying-nan;CHANG Xin-jie;ZHANG Ying-jian(The First Affiliated Hospital of Henan University of Science and Technology,Dept of Pediatric Surgery,Luoyang Henan 471000,China;The First Affiliated Hospital of Henan University of Science and Technology,Dept of Gastroenterology,Luoyang Henan 471000,China)
出处
《中国药理学通报》
CSCD
北大核心
2021年第9期1245-1250,共6页
Chinese Pharmacological Bulletin
基金
河南省医学科技攻关计划项目(No 182102310302)。
作者简介
王瑛(1974-),女,硕士,副主任医师,研究方向:新生儿出血坏死性小肠结肠炎临床与基础研究,E-mail:wangying197401@163.com;通信作者:张英剑(1970-),男,博士,主任医师,研究方向:炎症性肠病胃食管反流病,E-mail:zyjhkdyfy1268@163.com。
