miRNA-146a调控STAT3信号通路在坏死性小肠结肠炎新生大鼠中的作用  

Effect of miRNA-146a on STAT3 signaling pathway in neonatal rats with necrotizing enterocolitis

作　　者：贺静[1] 鲁利群[1] 杨欣[1] 闵晓兰[2] 黄莉[1] 邓国清[1] HE Jing;LU Li-qun;YANG Xin;MIN Xiao-lan;HUANG Li;DENG Guo-qing(Department of Paediatrics,First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,Sichuan,China;Department of Paediatrics,Second People′s Hospital of Yibin City,Yibin 644000,Sichuan,China)

机构地区：[1]成都医学院第一附属医院儿科,610500 [2]宜宾市第二人民医院儿科,644000

出　　处：《现代消化及介入诊疗》2020年第6期740-743,748,共5页Modern Interventional Diagnosis and Treatment in Gastroenterology

摘　　要：目的探讨miRNA-146a调控STAT3信号通路在坏死性小肠结肠炎(NEC)新生大鼠中的作用。方法选择新生雄性大鼠40只,分4组,每组10只。分别是对照组(A组)、模型组(B组)、阴性对照组(C组)、miRNA-146a agomir组(D组)。采用HE染色,光镜下观察各组大鼠肠组织病理形态学改变;ELISA检测各组大鼠回盲部肠组织中TNF-α、IL-1β表达水平;qRT-PCR检测各组大鼠回盲部肠组织中miRNA-146a、STAT3、IL-6;Western blot检测各组大鼠回盲部肠组织中STAT3、p-STAT3、IL-6。结果光镜结果显示,A组肠组织结构清晰,上皮完整,腺体排列规则、黏膜层及黏膜下层无充血水肿且无炎症细胞浸润;B组和C组肠组织坏死严重,腺体排列紊乱,部分绒毛坏死、脱落,黏膜下层重度水肿,存在大量炎症细胞浸润;D组肠黏膜及黏膜下层可见轻度水肿,有少量炎症细胞浸润,肠组织结构坏死情况减轻,腺体排列稍紊乱。与A组相比,B组、C组大鼠肠组织miRNA-146a表达水平降低而D组miRNA-146a表达水平升高,差异具有统计学意义(P<0.05);B组、C组大鼠肠组织TNF-α、IL-1β含量、STAT3、IL-6 mRNA和蛋白表达水平均显著升高(均P<0.05);过表达miRNA-146a agomir后,大鼠肠组织TNF-α、IL-1β含量、STAT3、IL-6 mRNA和蛋白表达水平均显著降低(均P<0.05)。结论NEC大鼠IL-6/STAT3信号通路激活,炎症水平升高,肠组织损伤严重;过表达miRNA-146a可减轻NEC炎症水平,改善肠组织损伤情况,其机制可能与miRNA-146a抑制IL-6/STAT3信号通路活化有关。Objective To explore the role of miRNA-146a in regulating STAT3 signaling pathway in neonatal rats with necrotizing enterocolitis(NEC).Methods Neonatal male rats were selected and divided into four groups with 10 rats in each group.They were control group(group A),model group(group B),miRNA negative control group(group C),miRNA-146a agomir group(group D).Histopathological changes of the intestine of rats in each group were observed under light microscope by HE staining.The expression of TNF-αand IL-1βin ileocecal tissues of rats in each group was detected by ELISA,qRT-PCR method was used to detect the miRNA-146a、STAT3、IL-6,and Western blot method was used to detect the STAT3、p-STAT3、IL-6 in ileocecal tissue of rats.Results The results of light microscopy showed that the intestinal tissue structure of group A was clear,the epithelium was complete,the arrangement of glands was regular,the mucosa and submucosa were free of hyperemia,edema and infiltration of inflammatory cells;there were severe necrosis of intestinal tissue,disordered arrangement of glands,necrosis and abscission of some villi,severe edema of submucosa,and infiltration of a large number of inflammatory cells,and there were a lot of inflammatory cells infiltrated in group B and C;the intestinal mucosa and submucosa of group D were slightly edematous.A small amount of inflammatory cells was infiltrated,the necrosis of intestinal tissue was reduced,and the arrangement of glands was slightly disordered.Compared with group A,the expression level of miRNA-146a in intestinal tissue of group B and group C was decreased,while the expression level of miRNA-146a in group D was increased(P<0.05).The levels of TNF-α,IL-1β,STAT3,IL-6 mRNA and protein were significantly increased in group B and group C(P<0.05),and the levels of TNF-α,IL-1β,STAT3,IL-6 mRNA and protein were significantly decreased since overpression of miRNA-146a agomir(P<0.05).Conclusion In NEC rats,IL-6/STAT3 signaling pathway was activated,the level of inflammation was increased,and

关 键 词：miRNA-146a STAT3信号通路 坏死性小肠结肠炎 新生大鼠 

分 类 号：R722.1[医药卫生—儿科] R574[医药卫生—临床医学]