疏肝和胃方通过抑制NF-κB通路调控M1巨噬细胞极化对反流性食管炎大鼠食管黏膜炎症的影响  

Effects of Shugan Hewei Recipe on esophageal mucosal inflammation in rats with reflux esophagitis by inhibiting NF-κB pathway and regulating macrophage M1 polarization

作　　者：杜梦蝶 王玮[1] 付文尚 孙永顺[1] DU Mengdie;WANG Wei;FU Wenshang;SUN Yongshun(Department of Spleen and Stomach Diseases,Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China)

机构地区：[1]上海中医药大学附属市中医医院脾胃病科,上海200071

出　　处：《上海中医药杂志》2024年第5期66-72,共7页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81874402,82174128)。

摘　　要：目的探讨疏肝和胃方通过抑制核因子-κB(NF-κB)通路调控M1巨噬细胞极化对反流性食管炎(RE)大鼠食管黏膜炎症的影响。方法将40只SD雄性大鼠随机分为假手术组(8只)和造模组(32只)。假手术组暴露食管下段及幽门,造模组予下食管括约肌切开术加十二指肠半结扎术。术后将造模成功的大鼠随机分为模型组、疏肝和胃方低剂量组、疏肝和胃方高剂量组和雷贝拉唑组。假手术组和模型组予蒸馏水灌胃,疏肝和胃方低、高剂量组分别予以10.49 g·kg^(-1)·d^(-1)、20.98 g·kg^(-1)·d^(-1)疏肝和胃方灌胃,雷贝拉唑组予雷贝拉唑(2.06 mg·kg^(-1)·d^(-1))灌胃,灌胃持续2周。采用苏木精-伊红(HE)染色观察食管组织病理学改变;采用Western blot法检测核因子-κB p65(NF-κB p65)、NF-κB抑制蛋白α(IκBα)的磷酸化情况,以及白细胞分化抗原86(CD86)、甘露糖受体(CD206)的表达;采用实时荧光定量逆转录聚合酶链式反应(RT-qPCR)法检测肿瘤坏死因子-α(TNF-α)、白介素-1β(IL^(-1β))、转化生长因子-β(TGF-β)mRNA表达。结果HE染色结果显示,模型组鳞状上皮增生,炎症细胞浸润;疏肝和胃方低、高剂量组和雷贝拉唑组组织结构正常,基底层血管湖少且小,无炎症细胞浸润。与假手术比较,模型组CD86、磷酸化IκBα(pIκBα)/IκBα、核因子-κB磷酸化p65(NF-κB pp65)/p65蛋白,以及TNF-α、IL^(-1β)mRNA表达升高(P<0.05)。与模型组比较,疏肝和胃方低、高剂量组和雷贝拉唑组CD86蛋白以及TNF-α、IL^(-1β)mRNA表达下降(P<0.05),疏肝和胃方高剂量组和雷贝拉唑组pIκBα/IκBα、pp65/p65表达下降(P<0.05),但疏肝和胃方低剂量组与模型组pIκBα/IκBα、pp65/p65的表达差异无统计学意义(P>0.05)。与假手术组比较,模型组CD206表达减少(P<0.05),TGF-βmRNA表达呈下降趋势但差异无统计学意义(P>0.05),疏肝和胃方低、高剂量组和雷贝拉唑组CD206表达升高(P<0.05)。与模型组比�Objective To explore the effects of Shugan Hewei Recipe on esophageal mucosal inflammation in rats with reflux esophagitis(RE)by inhibiting the nuclear factor-kappa B(NF-κB)pathway and regulating macrophage M1 polarization.Methods Forty male SD rats were randomly divided into a sham operation group(n=8)and a molding group(n=32).Rats in the sham operation group underwent exposure of the lower esophagus and pylorus,while those in the molding group received a lower esophageal sphincter incision(cardia myotomy)and partial duodenal ligation.Postoperatively,successfully modeled rats were randomly divided into the model group,low-dose Shugan Hewei Recipe group,high-dose Shugan Hewei Recipe group,and rabeprazole group.The sham and model groups were administered distilled water,whereas the Shugan Hewei recipe was administered to the low and high-dose groups at dosages of 10.49 g·kg^(-1)·d^(-1)and 20.98 g·kg^(-1)·d^(-1),respectively,and the rabeprazole group received rabeprazole,all via gavage for 2 weeks.Esophageal tissues were stained by Hematoxylin-Eosin(HE)to observe pathological changes.The phosphorylation of NF-κB p65 and NF-κB inhibitor alpha(IκBα),and the expression of cluster of differentiation 86(CD86)and mannose receptor cluster of differentiation 206(CD206)were detected by Western blot;and the mRNA expressions of tumor necrosis factor-alpha(TNF-α),interleukin-1beta(IL^(-1β)),and transforming growth factor-beta(TGF-β)were measured by real-time fluorescence quantitative reverse transcription-polymerase chain reaction(RT-qPCR).Results HE staining revealed squamous epithelial hyperplasia and inflammatory cell infiltration in the model group,whereas the low and high-dose Shugan Hewei Recipe groups and the rabeprazole group showed normal histological structure,reduced and smaller basal layer vascular lakes,and no inflammatory cell infiltration.Compared with the sham operation group,the model group exhibited increased expressions of CD86,phosphorylated IκBα(pIκBα)/IκBα,phosphorylated NF-κB p65(NF-κ

关 键 词：反流性食管炎 疏肝和胃方 核因子-ΚB信号通路 作用机制 大鼠模型 中药研究 

分 类 号：R285.5[医药卫生—中药学]