靶向抑制表皮生长因子受体可通过干扰血管内皮细胞间充质转分化治疗肝纤维化  

Targeted Inhibition of Epidermal Growth Factor Receptor Improves Hepatic Fibrosis by Interfering with Endothelial-to-Mesenchymal Transition

作　　者：曹兴旺 杨思艺 袁静簃 郭庆 曾韵桃 谢成亮 毕涛 魏微 Cao Xingwang;Yang Siyi;Yuan Jingyi;Guo Qing;Zeng Yuntao;Xie Chengliang;Bi Tao;Wei Wei(School of Integrated Traditional Chinese and Western Medicine,Southwest Medical University,Luzhou 646000,China;National Traditional Chinese Medicine Clinical Research Base·The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学中西医结合学院,泸州646000 [2]国家中医临床研究基地建设单位·西南医科大学附属中医医院,泸州646000

出　　处：《成都医学院学报》2023年第1期27-32,共6页Journal of Chengdu Medical College

基　　金：四川省教育厅重点项目(自然科学)(No:17ZA0451);四川省卫生和计划生育委员会科研课题(普及应用项目)(No:16PJ532)。

摘　　要：目的观察靶向性抑制表皮生长因子受体(EGFR)的抑制剂AZ-5104对小鼠肝纤维化症状的影响,探讨AZ-5104改善肝纤维化的作用机制。方法选用了12只雄性C57小鼠,随机分为常规组、模型组和给药组,每组4只。除常规组外,其余两组腹腔注射浓度为20%(0.8 g/kg)的CCl4,3 d/次,共注射4次,同时喂养高脂饲料和含有5%蔗糖的饮用水。给药组小鼠腹腔注射AZ-5104,CCl4注射完成后次日注射药物,第3天不做处理,重复4次上述操作,第4次药物注射完成后,处死小鼠取材,对小鼠肝脏进行常规病理学检测以及免疫荧光染色。结果CCl4所诱导的模型组与常规组比较,肝小叶内部结构严重损坏,周围纤维结缔组织数量明显增多,并且有大小不等的假小叶形成;给药组较模型组肝纤维化症状明显改善,肝纤维化过程中血管内皮细胞间充质转分化(End MT)明显减弱。结论AZ-5104作为靶向性抑制EGFR的抑制剂可改善小鼠肝纤维化,其抗纤维化效果的发挥可能与抑制纤维化过程中End MT密切相关。Objective To observe the effect of epidermal growth factor receptor(EGFR) inhibitor AZ-5104 on hepatic fibrosis in mice and explore the mechanism of AZ-5104 in improving hepatic fibrosis. Methods A total of 12 male C57 mice were randomly divided into normal group(n=4),model group(n=4) and administration group(n=4). The model group and the administration group received 20%(0.8 g/kg) intraperitoneal injection of carbon tetrachloride(CCl4) once every 3 days for a total of 4 times,and were fed with high-fat feed and drinking water containing 5% sucrose. The administration group was intraperitoneally injected with AZ-5104 the next day after the injection of CCl4,and no treatment was done on the third day. And the above operations were repeated 4 times. After the fourth drug injection,the mice were killed for sampling. Routine pathological examination and immunofluorescence staining were performed on the sampled mice liver. Results Compared with the normal group,the model group induced by CCl4 showed obvious damage of hepatic lobule structure,obvious increase of fibrous connective tissue and formation of pseudolobule of different sizes. Compared with the model group,the administration group showed significant improvement of hepatic fibrosis symptoms and decreased endothelialto-mesenchymal transition(End MT) during hepatic fibrosis. Conclusion AZ-5104,a targeted inhibitor of EGFR,can ameliorate liver fibrosis in mice. The antifibrotic effect of AZ-5104 may be related to its inhibition of End MT in the process of hepatic fibrosis.

关 键 词：表皮生长因子受体 血管内皮细胞间充质转分化 肝纤维化 

分 类 号：R575.1[医药卫生—消化系统] R575.2[医药卫生—内科学]