活血通降方对反流性食管炎大鼠食管损伤和xCT/VEGF-B/GPX4信号通路的影响  

Effects of Huoxue Tongjiang Decoction on Esophageal Injury and xCT/VEGF-B/GPX4 Signaling Pathway in Rats with Reflux Esophagitis

作　　者：刘琰 唐艳萍[2] 李培彩[2] 刘磊 刘茜 杨磊[2] 郝旭雯[2] LIU Yan;TANG Yanping;LI Peicai;LIU Lei;LIU Xi;YANG Lei;HAO Xuwen(Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Nankai Hospital,Tianjin 300100,China)

机构地区：[1]天津中医药大学研究生院,天津301617 [2]天津市南开医院,天津300100

出　　处：《中国中医药信息杂志》2022年第12期87-92,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82074213、81573737)。

摘　　要：目的观察活血通降方对反流性食管炎(RE)大鼠食管损伤的影响,从xCT/VEGF-B/GPX4铁死亡信号通路探讨其作用机制。方法采用改良部分贲门肌切开术+外置幽门部分结扎术制备RE大鼠模型。将成模大鼠随机分为模型组及活血通降方低、高剂量组,每组12只,另取12只作为空白组。造模成功当日开始给药,活血通降方低、高剂量组给药剂量分别为3.68、7.35 g/(kg·d),每日早晚各1次,连续灌胃14 d,空白组和模型组予5 mL生理盐水灌胃。观察大鼠食管黏膜损伤情况,HE染色观察黏膜组织病理变化,试剂盒检测食管组织丙二醛(MDA)、谷胱甘肽(GSH)、活性氧(ROS)含量,Western blot检测食管组织胱氨酸/谷氨酸反向转运体(xCT)、血管内皮生长因子B(VEGF-B)、谷胱甘肽过氧化物酶4(GPX4)蛋白表达,ELISA检测血清白细胞介素(IL)-1β、IL-17、IL-10含量。结果与空白组比较,模型组大鼠食管黏膜损伤明显,肉眼及病理评分显著升高,食管组织MDA、ROS含量增加,GSH含量减少,xCT、VEGF-B、GPX4蛋白表达降低,血清IL-1β、IL-17含量增加,IL-10含量减少,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,活血通降方低、高剂量组大鼠食管黏膜损伤改善,肉眼及病理评分显著降低,食管组织MDA、ROS含量减少,xCT、VEGF-B、GPX4蛋白表达升高,血清IL-1β、IL-17含量减少,IL-10含量增加,活血通降方高剂量组大鼠食管组织GSH含量增加,差异均有统计学意义(P<0.05,P<0.01)。结论活血通降方可缓解RE大鼠食管黏膜炎症,修复食管损伤,其机制可能与激活xCT/VEGF-B/GPX4信号通路,增加其抗氧化性,提高抗氧化因子GSH水平,清除食管中过多的ROS,调节相关炎症因子水平,影响食管细胞铁死亡有关。Objective To observe the effects of Huoxue Tongjiang Decoction on esophageal injury in rats with reflux esophagitis(RE);To discuss its mechanism of action from the xCT/VEGF-B/GPX4 ferroptosis signaling pathway.Methods RE model rats were prepared by modified partial cardiac myotomy+external pyloric partial ligation.The model rats were randomly divided into model group,Huoxue Tongjiang Decoction low-and highdosage groups,with 12 rats in each group,another 12 rats were taken as the blank group.After the successful modeling,the drug was administered on the same day.Huoxue Tongjiang Decoction low-and high-dosage groups received 3.68 and 7.35 g/(kg·d)for gavage respectively,once in the morning and once in the evening,for 14 days.The control group and model group were given 5 mL normal saline for gavage.The injury of esophageal mucosa in rats were observed,HE staining was used to observe the histopathological changes of esophageal mucosa,the contents of malondialdehyde(MDA),glutathione(GSH)and reactive oxygen species(ROS)in esophageal tissue were detected by corresponding kit.The expressions of cystine/glutamate antiporter(xCT),vascular endothelial growth factor B(VEGF-B)and glutathione peroxidase 4(GPX4)protein in esophageal tissue were detected by Western blot,the contents of interleukin(IL)-1β,IL-17 and IL-10 in serum were detected by ELISA.Results Compared with the control group,the esophageal mucosa was significantly damaged of the rats in model group,the gross and pathological scores significantly increased,the contents of MDA and ROS in esophageal tissue increased,the content of GSH reduced,the proteins expression of xCT,VEGF-B and GPX4 decreased,the contents of serum IL-1βand IL-17 increased,and the content of IL-10 reduced,all with statistical significance(P<0.05,P<0.01).Compared with the model group,the damages of esophageal mucosa of the rats in Huoxue Tongjiang Decoction low-and high-dosage groups were improved,the gross and pathological scores were significantly decreased,the contents of MDA and ROS in e

关 键 词：活血通降方 反流性食管炎 xCT/VEGF-B/GPX4信号通路 铁死亡 食管损伤 

分 类 号：R285.5[医药卫生—中药学]