IL-17A基因敲除对急性胰腺炎模型小鼠严重程度的影响  

Effects of generic IL-17A gene knockout on the severity of acute pancreatitis in mice

作　　者：吴咏姿 刘诗雨 张潇颖[1] 李燕妮 蔡文浩[1] 刘婷婷[1] 夏庆[1] 黄伟[1,3,4] WU Yongzi;LIU Shiyu;ZHANG Xiaoying;LI Yanni;CAI Wenhao;LIU Tingting;XIA Qing;HUANG Wei(West China Center of Excellence for Pancreatitis,Institute of Integrated Traditional Chinese and Western Medicine,West China Hospital,Sichuan University,Chengdu 610041,P.R.China;Department of Gastroenterology,West China Hospital,Sichuan University,Chengdu 610041,P.R.China;West China Biobanks,West China Hospital,Sichuan University,Chengdu 610041,P.R.China;Frontiers Science Center for Disease-Related Molecular Network,West China Hospital,Sichuan University,Chengdu 610041,P.R.China)

机构地区：[1]四川大学华西医院中西医结合中心,胰腺炎中心,成都610041 [2]四川大学华西医院消化内科,成都610041 [3]四川大学华西医院生物样本库,成都610041 [4]四川大学疾病分子网络前沿科学中心,成都610041

出　　处：《中国普外基础与临床杂志》2024年第2期161-168,共8页Chinese Journal of Bases and Clinics In General Surgery

基　　金：四川省科技计划项目-重点研发计划。

摘　　要：目的探究IL-17A基因敲除对急性胰腺炎(acute pancreatitis,AP)模型小鼠胰腺及肠道屏障的影响。方法使用IL-17A全身性基因敲除(generic IL-17A gene knockout,IL-17AKO)小鼠及其同窝野生型(wild type,WT)小鼠构建雨蛙素(cerulein,CER)诱导的轻症AP(CER-AP)及牛磺胆酸钠(sodium taurocholate,NaTC)诱导的重症AP模型(NaTC-AP)。CER-AP模型实验:小鼠随机分为3组,分别为WT对照组、WT模型组和IL-17AKO模型组(n=5),WT模型组和IL-17AKO模型组小鼠腹腔注射CER 7次[50μg/(kg·h)],WT对照组小鼠腹腔注射等量生理盐水。于第1次注射后第12 h处死,收集小鼠血清检测淀粉酶、脂肪酶及白细胞介素-6(interleukin-6,IL-6)水平,收集胰腺组织进行苏木精-伊红(HE)染色。NaTC-AP模型实验:WT小鼠随机分为假手术组(n=3)和模型组(n=6),IL-17AKO小鼠亦随机分为假手术组(n=3)和模型组(n=6)。假手术组小鼠只行开关腹手术,模型组小鼠经逆行胰胆管泵入50μL的3.5%NaTC生理盐水溶液。于术后第24 h处死小鼠,收集小鼠血清检测淀粉酶、脂肪酶及IL-6水平,取胰腺组织进行HE染色,取肠道组织进行阿利新蓝-过碘酸雪夫染色、双花扁豆凝集素染色及肠道荧光细菌原位杂交。结果CER-AP模型实验:与WT模型组相比,IL-17AKO模型组小鼠的血清淀粉酶、脂肪酶和IL-6水平,以及胰腺病理总分、水肿评分、炎症评分及坏死评分的差异均无统计学意义(P>0.05)。NaTC-AP模型实验:与模型组WT小鼠相比,模型组IL-17AKO小鼠的血清淀粉酶和脂肪酶水平,以及胰腺病理总分、水肿评分、炎症评分及坏死评分的差异均无统计学意义(P>0.05),但IL-6水平升高(P<0.05);与假手术组WT小鼠比较,假手术组IL-17AKO小鼠的回肠及结肠组织中糖基化黏蛋白表达水平降低、黏液层结构紊乱及细菌侵袭增加。结论IL-17AKO对AP胰腺及肠道屏障损伤无显著保护作用,但IL-17AKO小鼠在造模前已出现全身炎症反应、肠道屏障受Objective To investigate the effects of generic interleukin(IL)-17A gene knockout(IL-17AKO)on pancreatic and intestinal barrier on acute pancreatitis(AP)in mice.Methods IL-17AKO mice and their wild type(WT)littermates were employed to induce AP using cerulein(CER)and sodium taurocholate(NaTC).In the CER-AP experiment,mice were randomly divided into three groups:WT control group,WT model group,and IL-17AKO model group(n=5).Mice in the model group were intraperitoneally injected with CER[50μg/(kg·h),7 injections],and control group received intraperitoneal injection the same amount of 0.9%NaCl.The mice were sacrificed at 12 hours after the first injection of CER.The levels of serum amylase,lipase and IL-6 were detected,and the pancreas was stained with hematoxylin-eosin(HE).In the NaTC-AP experiment,WT mice were randomly divided into sham group(n=3)and operation model group(n=6).Similarly,IL-17AKO mice were also randomly allocated to sham group(n=3)and operation model group(n=6).The mice in the sham group underwent a surgical procedure on the abdomen only,whereas in the model group,50μL 3.5%NaTC dissolved in saline solution was pumped into the pancreatobiliary duct.Serum amylase,lipase,and IL-6 levels were detected.Pancreas was stained with HE,and intestine was stained with Alcian blue-periodic acid-Schiff,Dolichos Biflorus Agglutinin and bacteria fluorescence in situ hybridization.Results In the CER-AP experiment,there were no significant differences in serum amylase,lipase,IL-6,and pathological changes including edema,inflammation,necrosis,and total pathological score of the pancreas between IL-17AKO and WT mice(P>0.05).In the NaTC-AP experiment,compared to the WT model group,IL-17AKO did not significantly impact serum amylase,lipase,and pancreatic pathological changes(P>0.05).However,it did lead to an increased level of IL-6(P<0.05),and showed no significant protective effect on intestinal injury in NaTC-AP.Compared to WT mice of sham group,IL-17AKO mice of sham group exhibited decreased expressions of glycosy

关 键 词：急性胰腺炎 肠道屏障 白细胞介素-17A 

分 类 号：R576[医药卫生—消化系统]