类固醇受体辅活化子-3对严重烧伤小鼠肠黏膜屏障功能损伤的影响  

Impact of steroid receptor coactivator-3 on intestinal mucosal barrier function damage in severely burned mice

作　　者：杨宇 易庆军 李军 张永洪 文婷婷 YANG Yu;YI Qingjun;LI Jun;ZHANG Yonghong;WEN Tingting(Department of Anesthesiology,Mianyang Central Hospital,The Affiliated Mianyang Hospital,School of Medcine of UESTC,Mianyang,Sichuan 621000,China;Department of Pediatrics,Mianyang Central Hospital,The Affiliated Mianyang Hospital,School of Medcine of UESTC,Mianyang,Sichuan 621000,China)

机构地区：[1]电子科技大学医学院附属绵阳医院、绵阳市中心医院麻醉科,四川绵阳621000 [2]电子科技大学医学院附属绵阳医院、绵阳市中心医院儿科,四川绵阳621000

出　　处：《安徽医药》2024年第2期235-240,I0002,共7页Anhui Medical and Pharmaceutical Journal

基　　金：创伤、烧伤与复合伤国家重点实验室开放基金资助(SKLKF202014)。

摘　　要：目的探究类固醇受体辅活化子-3(SRC-3)对严重烧伤小鼠肠黏膜屏障功能损伤的影响。方法2022年1―4月将SPF级雌性SRC-3基因敲除(SRC-3-/-)小鼠作为对实验组(n=36),并以野生型(SRC-3+/+)小鼠作为对照组(n=36),两组小鼠均诱导建立背部30%体表总面积(TBSA)Ⅲ度烧伤模型。在烧伤后第1、3、5天时,荧光素异硫氰酸酯-葡聚糖(FITC-dextran)灌胃检测肠道通透性,酶联免疫吸附测定(ELISA)法检测血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平和血浆二胺氧化酶(DAO)活性以及内毒素(ET)水平,苏木精-伊红(HE)和阿尔新蓝-过碘酸-希夫(AB-PAS)染色评估肠黏膜损伤和杯状细胞黏液分泌情况,免疫组织化学(IHC)染色检测黏蛋白2(Muc2)的表达,蛋白质印迹法检测肠黏膜中Muc2、IL-6和TNF-α蛋白表达。结果在烧伤后第1、3、5天时,与对照组(SRC-3+/+小鼠)相比,实验组SRC-3-/-小鼠血清FITC-dextran浓度[(1156.21±107.65)μg/L比(685.14±79.36)μg/L、(1425.81±115.36)μg/L比(743.72±82.29)μg/L、(1613.27±120.94)μg/L比(824.35±85.44)μg/L]、血浆DAO活性和ET水平、肠黏膜损伤评分、PAS+杯状细胞数量、血清和肠黏膜中IL-6、TNF-α水平显著升高,AB+杯状细胞数量、肠黏膜中Muc2表达水平显著降低(P<0.05)。结论SRC-3缺失可以在严重烧伤后损害杯状细胞的分化成熟,减少肠黏液的合成与分泌,加重肠黏膜屏障功能障碍。Objective To investigate the impact of steroid receptor coactivator-3(SRC-3)on the damage of intestinal mucosal barrier function in severely burned mice.Methods From January to April 2022,the SPF female SRC-3 knockout(SRC-3-/-)mice were regard⁃ed as the experimental group(n=36),and the wild-type(SRC-3+/+)mice were regarded as the control group(n=36),both groups of mice were induced to establish a 30%total body surface area(TBSA)third-degree burn model on the back.On the 1st,3rd,and 5th days af⁃ter burn,fluorescein isothiocyanate-dextran(FITC-dextran)was administered by gavage to detect intestinal permeability,the levels of serum interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α),plasma diamine oxidase(DAO)activity,and the level of endotoxin(ET)were detected by enzyme-linked immunosorbent assay(ELISA),hematoxylin-eosin(HE)and alcian blue-periodic acid-Schiff(ABPAS)staining were used to evaluate intestinal mucosal injury and goblet cell mucus secretion,the expression of mucin 2(Muc2)was de⁃tected by immunohistochemical(IHC)staining,Western blotting was used to detect the protein expressions of Muc2,IL-6 and TNF-αin intestinal mucosa.Results On the 1st,3rd,and 5th days after burn,compared with the control group(SRC-3+/+mice),the serum FITCdextran concentration[(1156.21±107.65)μg/L vs.(685.14±79.36)μg/L,(1425.81±115.36)μg/L vs.(743.72±82.29)μg/L,(1613.27±120.94)μg/L vs.(824.35±85.44)μg/L],plasma DAO activity,level of ET,intestinal mucosal injury score,the number of PAS+goblet cells,the levels of IL-6 and TNF-αin serum and intestinal mucosa of SRC-3-/-mice in the experimental group were obviously increased,the number of AB+goblet cells and the expression level of Muc2 in intestinal mucosa were obviously decreased(P<0.05).Conclusion SRC-3 deletion can impair the differentiation and maturation of goblet cells after severe burn,reduce the synthesis and secretion of in⁃testinal mucus,and aggravate the dysfunction of intestinal mucosal barrier.

关 键 词：烧伤 类固醇受体辅活化子-3 肠黏膜屏障功能 杯状细胞 小鼠 

分 类 号：R644[医药卫生—外科学]