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

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［( 1 156.21±107.65) μg/L比( 685.14±79.36)μg/L、(1 425.81±115.36)μg/L比( 743.72±82.29)μg/L、(1 613.27±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。

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

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 (AB-PAS) 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-α in intestinal mucosa.Results On the 1st, 3rd, and 5th days after burn, compared with the control group (SRC-3+/+ mice), the serum FITC-dextran concentration[(1 156.21±107.65)μg/L vs. (685.14±79.36)μg/L, (1 425.81±115.36)μg/L vs. (743.72±82.29)μg/L, (1 613.27± 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+ gobletcells, the levels of IL-6 and TNF-α in 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.