柴胡皂苷A对反流性食管炎大鼠炎性损伤的影响及机制研究  

Effect and Mechanism of Saikosaponin A on Inflammatory Injury in Rats with Reflux Esophagitis

作　　者：杨芳 胡以撒 YANG Fang;HU Yisa(Zhejiang University of Traditional Chinese Medicine,Lishui 323400,China;General Medicine of the First Affiliated Hospital of Ningbo University,Ningbo 315201,China)

机构地区：[1]浙江中医药大学,浙江丽水323400 [2]宁波大学附属第一医院全科医学,浙江宁波315201

出　　处：《中国药学杂志》2025年第3期250-256,共7页Chinese Pharmaceutical Journal

基　　金：2021年浙江省卫生健康科技计划项目资助(2021RC124)。

摘　　要：目的探讨柴胡皂苷A(saikosaponin A,SA)调节白细胞介素(interleukin,IL)-6/酪氨酸激酶2(tyrosine kinase 2,JAK2)/信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)通路对反流性食管炎(reflux esophagitis,RE)大鼠炎性损伤的影响。方法SD大鼠随机分为RE组、正常组、SA低剂量组(灌胃12.5 mg·kg^(-1) SA)、SA高剂量组(灌胃50 mg·kg^(-1) SA)、奥美拉唑组(灌胃2 mg·kg^(-1)奥美拉唑)、SA高剂量+IL-6激活剂重组大鼠IL-6蛋白(recombinant rat IL-6 protein,rRIL-6)组(灌胃50 mg·kg^(-1) SA+腹腔注射0.05 mg·kg^(-1) rRIL-6),每组12只。除正常组外,其他组大鼠均需通过结扎前胃+部分结扎外置幽门法构建RE模型,建模成功第二天开始给药,给药1天1次,持续2周。检测大鼠食管黏膜损伤率;苏木精-伊红染色(hematoxylin-eosin staining,HE)检测食管组织的病理学变化;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测食管组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、环氧化酶-2(cyclooxygenase-2,COX-2)、IL-8水平;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(terminal dexynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)检测食管组织中的细胞凋亡;免疫组化染色检测食管组织中紧密连接蛋白-5(claudin-5)表达;Western blot检测食管组织中IL-6、磷酸化JAK2(p-JAK2)、p-STAT3蛋白。结果与正常组相比,RE组大鼠食管组织紧密性降低,且有大量炎性细胞浸润,食管黏膜损伤率、食管组织中TNF-α、COX-2、IL-8水平、细胞凋亡率、IL-6、磷酸化-JAK2(p-JAK2)、p-STAT3蛋白表达升高,食管组织中claudin-5平均光密度值降低(P<0.05);与RE组相比,SA低剂量组、SA高剂量组、奥美拉唑组大鼠食管组织病理损伤减轻,食管黏膜损伤率、食管组织中TNF-α、COX-2、IL-8水平、细胞凋亡率、IL-6、p-JAK2、p-STAT3蛋白表达降低,食管组织中claudin-5平均光密度值升高(P<0.05);�OBJECTIVE To investigate the effect of saikosaponin A(SA)on inflammatory injury in rats with reflux esophagitis(RE)by regulating the interleukin(IL)-6/tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.METHODS SD rats were randomly divided into RE group,normal group,SA low-dose group(gavage of 12.5 mg·kg^(-1)SA),SA high-dose group(gavage of 50 mg·kg^(-1)SA),omeprazole group(gavage of 2 mg·kg^(-1)omeprazole),SA high-dose+IL-6 activator recombinant rat IL-6 protein(rRIL-6)group(gavage of 50 mg·kg^(-1)SA+intraperitoneal injection of 0.05 mg·kg^(-1)rRIL-6),with 12 rats in each group.Except for the normal group,rats in all other groups were required to undergo RE model construction through fore-stomach ligation combined with partial ligation of the external pylorus.After successful modeling,the drug was administered once a day for 2 weeks.The damage rate of esophageal mucosa was detected.Hematoxylin-eosin staining(HE)was applied to detect pathological changes in esophageal tissue.Enzyme-linked immunosorbent assay(ELISA)was applied to detect levels of tumor necrosis factor-α(TNF-α),cyclooxygenase-2(COX-2),and IL-8 in esophageal tissue.Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining was applied to detect cell apoptosis in esophageal tissue.Immunohistochemical staining was applied to detect the expression of claudin-5 in esophageal tissue.Western blot was applied to detect IL-6,p-JAK2,and p-STAT3 proteins in esophageal tissue.RESULTS Compared with the normal group,the esophageal tissue compactness of rats in the RE group decreased,and there was a large amount of inflammatory cell infiltration,the incidence of esophageal mucosal injury,levels of TNF-α,COX-2,IL-8 in esophageal tissue,apoptosis rate,and the expression of IL-6,p-JAK2,and p-STAT3 proteins increased,while the average optical density of claudin-5 in esophageal tissue decreased(P<0.05).Compared with the RE group,the pathological damage to the esophageal tissue of rats in the SA low

关 键 词：柴胡皂苷A 白细胞介素-6/酪氨酸激酶2信号转导 转录激活因子3通路 反流性食管炎 炎症 

分 类 号：R966[医药卫生—药理学]