清郁和降汤对反流性食管炎模型大鼠食管组织LPS/TLR4/NF-κB通路及食管黏膜屏障的影响  

Effect of Qingyu Hejiang Decoction(清郁和降汤)on LPS/TLR4/NFκB Pathway and Esophageal Mucosal Barrier in Reflux Esophagitis Model Rats

作　　者：黄雨晴[1] 周易 黄鹤[1,2] 叶松 HUANG Yuqing;ZHOU Yi;HUANG He;YE Song(Hubei University of Chinese medicine,Wuhan,430065;Hubei Provincial Hospital of Traditional Chinese Medicine)

机构地区：[1]湖北中医药大学,湖北省武汉市430065 [2]湖北省中医院

出　　处：《中医杂志》2022年第22期2170-2178,共9页Journal of Traditional Chinese Medicine

基　　金：北京市医院管理中心重点医学专业发展计划(ZYLX202140)。

摘　　要：目的 探讨清郁和降汤治疗反流性食管炎(RE)的可能作用机制。方法 60只雄性SD大鼠中随机选择10只为假手术组,另外50只采用“前胃结扎+外置幽门部分结扎术”建立反流性食管炎模型。将造模成功的40只大鼠随机分成模型组、清郁和降汤组、雷贝拉唑+莫沙比利组和中西药联用组,每组10只。造模后假手术组及模型组分别予蒸馏水1 ml/100 g灌胃,清郁和降汤组予浓度为1.58 g/ml的清郁和降汤灌胃,雷贝拉唑+莫沙比利组予浓度为0.21 mg/ml的雷贝拉唑钠肠溶胶囊溶液和浓度为0.16 mg/ml的枸橼酸莫沙比利分散片溶液灌胃,中西药联用组予清郁和降汤、雷贝拉唑钠肠溶胶囊、枸橼酸莫沙比利分散片灌胃,剂量同上。各组灌胃量均为1 ml/100 g,持续14天。观察大鼠食管组织的病理学改变;检测大鼠血清中及食管组织中脂多糖(LPS)、白细胞介素1β (IL-1β)、白细胞介素6 (IL-6)、白细胞介素8 (IL-8)含量;检测食管组织中Toll样受体4 (TLR4)、核转录因子κB (NF-κB) p65、封闭蛋白1 (Cldn1)、封闭蛋白4 (Cldn4)mRNA及蛋白表达水平。结果 与假手术组比较,模型组大鼠食管黏膜损伤严重,肉眼观察可见充血、糜烂或溃疡,镜下可见食管鳞状上皮增厚并伴有基底细胞增生,黏膜固有层乳头延伸,大量炎性细胞浸润;与模型组比较,各给药组食管黏膜损伤明显减轻。与假手术组比较,模型组大鼠血清及食管组织LPS、IL-1β、IL-6、IL-8表达升高(P<0.01),食管组织TLR4、NF-κB p65 mRNA和蛋白表达升高,Cldn1、Cldn4 mRNA和蛋白表达降低(P<0.01);与模型组比较,各给药组大鼠血清及食管组织LPS、IL-1β、IL-6、IL-8表达降低(P<0.01),食管组织TLR4、NF-κB p65 mRNA及蛋白表达降低,Cldn1、Cldn4 mRNA及蛋白表达升高(P<0.05或P<0.01)。与中西药联用组比较,清郁和降汤组、雷贝拉唑+莫沙比利组大鼠血清及食管组织LPS、IL-1β、IL-6、IL-8表达明显升高,TLR4、NF-�ObjectiveTo explore the potential mechanism of Qingyu Hejiang Decoction(清郁和降汤,QHD)inthe treatment of reflux esophagitis(RE).MethodsTen out of 60 male SD rats were randomly selected as shamoperation group,and the other 50 rats were treated with anterior gastric ligation and external pyloric partial ligation toestablish the RE model.Forty successful models were randomly divided into model group,QHD group,rabeprazole+mosapride group and integrated traditional Chinese and western medicine group(integrated group),with 10 rats ineach group.After modeling,the rats in the sham operation group and the model group were perfused with 1 ml/100 gof distilled water,while those in the QHD group were given 1.58 g/ml of QHD,and those in the rabeprazole+mosapride group were treated with 0.21 mg/ml of rabeprazole sodium enteric-coated capsule plus 0.16 mg/L ofmosapride citrate dispersible tablet;rats in the integrated medicine group were treated with QHD,rabeprazole,andmosapride,in the same administration way as mentioned above.All the interventions were given at the dose of 1 ml/100 g by gavage,for 14 days.The pathological changes of rat esophagus were observed,and the contents of lipopoly-saccharide(LPS),interleukin-1β(IL-1β),interleukin-6(IL-6)and interleukin-8(IL-8)in serum and esophagealtissue were detected.The m RNA levels and protein expressions of Toll-like receptor 4(TLR4),nuclear transcriptionfactorκB(NF-κB)p65,occludin 1(Cldn1)and occludin 4(Cldn4)in esophageal tissue were detected.Results compared to those in the sham operation group,the esophageal mucosa of the model group was seriously injured,andhyperemia,erosion or ulcer could be seen with naked eyes,as well as thickening of esophageal squamous epithelium,proliferation of basal cells,extension of lamina propria papilla and infiltration of a large number of inflammatory cellsseen under microscope.Compared to that in the model group,esophageal mucosal injury in other three interventiongroups was significantly alleviated.Compared to those in the sham oper

关 键 词：反流性食管炎 清郁和降汤 LPS/TLR4/NF-κB信号通路 食管黏膜屏障 炎症因子 

分 类 号：R285.5[医药卫生—中药学]