对羟基苯甲醛对实验性肠纤维化的作用机制  

Effect and mechanism of p-hydroxybenzaldehyde on experimental intestinal fibrosis

作　　者：卢曦[1] 马怡晗 覃兵 王宇晖 徐笑天 段小群[2,3] LU Xi;MA Yi-han;QIN Bing;WANG Yu-hui;XU Xiao-tian;DUAN Xiao-qun(School of Pharmacy,Guilin Medical University,Guilin Guangxi 541199,China;School of Biomedical Industry,Guilin Medical University,Guilin Guangxi 541199,China;Industrial Technology Research Institute,Guilin Medical University,Guilin Guangxi 541199,China)

机构地区：[1]桂林医学院药学院,广西桂林541199 [2]桂林医学院生物医药产业学院,广西桂林541199 [3]桂林医学院产业技术研究院,广西桂林541199

出　　处：《中国药理学通报》2023年第4期685-692,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82160615)。

摘　　要：目的基于小鼠肠纤维化模型、体外上皮间质转化(epithelial-mesenchymal transition,EMT)模型探讨对羟基苯甲醛(p-hydroxybenzaldehyde,HD)对小鼠肠纤维化的作用和机制。方法采用HE染色、Masson染色、免疫组化、qPCR、Western blot等实验方法验证HD对小鼠肠纤维化的作用及其机制。结果在体内实验中,相较于正常组,葡聚糖硫酸钠诱导的肠纤维化模型组小鼠结肠缩短,结肠组织病理评分升高,胶原容积分数(collagen volume fraction,CVF)升高,Ⅰ型胶原(collagenⅠ)明显表达升高。在使用4、10、25 mg·kg-1HD治疗后,相较于模型组,缓解了小鼠结肠缩短,且组织病理评分、CVF及collagenⅠ的表达呈剂量依赖性降低。而在体内外实验中,相较于模型组,HD都能够呈剂量依赖性抑制结肠组织和IEC-6细胞中EMT相关因子α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、波形蛋白(vimentin)、神经钙黏素(N-cadherin),升高上皮细胞钙黏蛋白(E-cadherin)的蛋白和mRNA表达。结论HD能够通过抑制EMT改善实验性肠纤维化。Aim To investigate the effect of p-hydroxybenzaldehyde(HD)on intestinal fibrosis in mice based on mouse intestinal fibrosis model and in vitro EMT model,and to explore the underlying mechanism.Methods HE staining,Masson staining,immunohistochemistry,qPCR,Western blot and other experimental methods were used to verify the effect of HD on intestinal fibrosis in mice and the potential mechanism.Results In vivo experiments showed that compared with the normal group,the DSS-induced intestinal fibrosis model group had shortened colon,increased colon histopathological score,increased collagen volume fraction,and significantly increased collagenⅠexpression.After treatment with 4,10,and 25 mg·kg-1 HD,compared with the model group,the colon shortening of mice was alleviated,and the histopathological score,collagen volume fraction and the expression of collagenⅠdecreased in a dose-dependent manner.Compared with the model group,in colon tissue and IEC-6 cells,HD could dose-dependently inhibit the protein and mRNA level expression of EMT-related factors such asα-SMA,Vimentin,N-cadherin,and increase the expression of E-cadherin.Conclusion HD can improve experimental intestinal fibrosis by inhibiting EMT.

关 键 词：对羟基苯甲醛 肠纤维化 炎症性肠病 胶原沉积 上皮间质转化 cadherin-switch 

分 类 号：R-332[医药卫生] R322.45R364.24R364.32R574.62