PPARδ激动剂GW501516调控细胞自噬对脓毒症小鼠肠黏膜屏障的影响  

Effects of PPARδagonist GW501516 on the intestinal mucosal barrier in septic mice by regulating autophagy

作　　者：陈凯立 王婷[1] 罗智浩 CHEN Kaili;WANG Ting;LUO Zhihao(Emergency Department,Guangdong Provincial Hospital of Chinese Medicine,Hainan Hospital,Haikou 570203,China)

机构地区：[1]广东省中医院海南医院急诊科,海口570203

出　　处：《中国医科大学学报》2025年第3期246-250,256,共6页Journal of China Medical University

基　　金：海南省自然科学基金(822QN475,822QN477)。

摘　　要：目的探讨过氧化物酶体增殖物激活受体δ(PPARδ)激动剂GW501516对脓毒症小鼠肠黏膜屏障的影响及其机制。方法将脓毒症模型小鼠分为model组、GW501516组和GW501516+雷帕霉素(Rap)组,另设置空白对照组(sham组)。通过HE染色观察小肠黏膜病理损伤,ELISA检测血清中D-乳酸(D-LA)和二胺氧化酶(DAO)水平及小肠组织中分泌型免疫球蛋白A(sIgA)和炎性细胞因子水平,透射电子显微镜下观察小肠组织自噬体数量,Western blotting检测小肠组织中PPARδ及自噬相关蛋白表达水平。结果与sham组比较,model组小鼠肠黏膜损伤严重,血清中D-LA和DAO水平及小肠组织中sIgA和炎性细胞因子水平显著升高,小肠组织出现过度自噬,PPARδ蛋白表达水平显著降低(均P<0.05)。与model组比较,GW501516组小鼠肠黏膜损伤明显减轻,血清中D-LA和DAO水平及小肠组织中sIgA和炎性细胞因子水平显著降低,小肠组织的过度自噬被抑制,PPARδ蛋白表达水平显著升高(均P<0.05)。Rap可显著抑制GW501516对脓毒症小鼠肠黏膜损伤的改善作用。结论GW501516可通过抑制细胞自噬改善脓毒症小鼠肠黏膜屏障损伤。Objective To investigate the mechanism of action of GW501516 on the intestinal mucosal barrier of septic mice.Methods Septic mice were divided into four groups:model,GW501516,GW501516+Rap,and a sham group.Hematoxylin and eosin staining was used to observe the pathological injury of the small intestinal mucosa.D-lactate(D-LA)and diamine oxidase(DAO)levels in serum,as well as secreted immunoglobulin A(sIgA)and inflammatory factor levels in small intestinal tissues,were measured using the enzyme-linked immunosorbent assay.The number of autophagosomes in the intestinal tissue was determined using transmission electron microscopy.Peroxisome proliferator activated receptorδ(PPARδ)and autophagy-related protein expression levels in small intestinal tissues were assessed using Western blotting.Results Compared with mice in the sham group,those in the model group exhibited severe intestinal mucosal injury,significantly higher D-LA and DAO serum levels,elevated sIgA and inflammatory factor levels in the small intestinal tissues,excessive autophagy in the small intestinal tissues,and significantly lower PPARδprotein levels(all P<0.05).Compared with the model group,intestinal mucosal injury was significantly reduced in the GW501516 group,with a significant decrease in serum D-LA and DAO levels,as well as reduced sIgA and inflammatory factor levels in small intestinal tissues.Excessive autophagy in small intestinal tissues was inhibited,and PPARδprotein levels were significantly increased(all P<0.05).However,Rap significantly inhibited the ameliorative effects of GW501516 on the intestinal mucosal injury in septic mice.Conclusion The PPARδagonist GW501516 improves intestinal mucosal barrier damage in septic mice by inhibiting autophagy.

关 键 词：脓毒症 GW501516 过氧化物酶体增殖物激活受体Δ 自噬 肠黏膜屏障损伤 

分 类 号：R574.5[医药卫生—消化系统]