首页|肝胃同治中药复方对胆汁反流大鼠胆汁酸代谢的影响

肝胃同治中药复方对胆汁反流大鼠胆汁酸代谢的影响

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目的 观察并探讨柴胡疏肝散与旋覆代赭汤的组合中药复方对胆汁反流大鼠外周血胆汁酸代谢的影响.方法 选取74 只SD雄性大鼠,24 只假手术组行腹腔切开和缝合术、50 只进行全胃切除+食管十二指肠吻合术造模,造模成功后分为模型组和中药组.术后 2 周、4 周、8 周的模型组与假手术组使用生理盐水分别灌胃0 周、2 周、6 周;术后8 周中药组以生药量9.3 g/(kg·d)的肝胃同治复方予以灌胃,连续给药6 周.各组大鼠灌胃量均为10 mL/(kg·d),经腹腔注射2%戊巴比妥钠麻醉后,开腹取食管和腹主动脉血.对食管组织进行脱水、包埋、切片和苏木素—伊红染色,观察大鼠食管组织病理学改变及癌前病变和癌变的出现率,同时用液相色谱—串联质谱法测定大鼠血清中11 种胆汁酸的水平.结果 术后2 周到术后8 周,模型组大鼠食管黏膜损伤严重程度递增,食管癌前病变和癌变的出现率逐渐上升,模型组术后8 周食管癌变出现率显著高于术后 2 周的模型组(P<0.05);中药组大鼠食管黏膜损伤改善,食管癌变出现率与模型组相比较显著降低(P<0.05).血清胆汁酸结果显示,与同期假手术组相比,模型组术后 2 周牛磺胆酸水平升高(P<0.05),牛磺鹅脱氧胆酸、脱氧胆酸水平下降(P<0.05);术后 4 周牛磺熊脱氧胆酸、牛磺脱氧胆酸水平升高(P<0.05),术后8 周牛磺胆酸水平升高(P<0.05);与术后8 周模型组比较,中药组甘氨胆酸、牛磺胆酸、牛磺鹅脱氧胆酸、牛磺脱氧胆酸水平都有所下降,但无统计学意义(P>0.05);胆酸、脱氧胆酸、熊脱氧胆酸、鹅脱氧胆酸、石胆酸、牛磺石胆酸水平有所升高,但无统计学意义(P>0.05).结论 肝胃同治中药复方具有防治胆汁反流引起食管癌变的效应,并可影响血清胆汁酸的代谢.
Effect of Ganwei Tongzhi TCM Compound on bile acid metabolism of rats with bile reflux
Objective To observe and investigate the effect of the TCM compound composed of Chaihu Shugan Powder and Xuanfu Daizhe Decoction on bile acid metabolism in peripheral blood of rats with bile reflux.Methods Among 74 SD male rats,24 in the sham group were performed laparotomy and abdominal suturing,and 50 rats were treated with complete gastrectomy and esophago-duodenostomy,which were divided into model group and TCM group after successful modeling.The model group and the sham operation group at 2,4,or 8 weeks after surgery were given intragastric administration with normal saline for 0,2,and 6 weeks,respectively.The TCM group at 8 weeks after surgery was intragastrically given with the Ganwei Tongzhi TCM Compound at a raw drug dose of 9.3 g/(kg·d)continuously for 6 weeks.The gavage volume of rats in each group was 10 mL/(kg·d).After rats anesthetized by an intraperitoneal injection of 2%pentobarbital,esophagus and the blood from abdominal aorta were collected.The esophageal tissues were dehydrated,embedded,sectioned and stained with hematoxylin-eosin.We then observed histopathological changes and the incidence of precancerous lesions and carcinogenesis of the rat esophagus,and measured the levels of 11 bile acids in rat serum by liquid chromatography-tandem mass spectrometry.Results From 2 weeks to 8 weeks after surgery,the severity of esophageal mucosa damage and the incidence of esophageal precancerous lesions and carcinogenesis of the model group were gradually increased.The incidences of esophageal carcinogenesis of the model group at 8 weeks after surgery was sig-nificantly higher than those of the model group at 2 weeks after surgery(P<0.05).The damages of esophageal mucosa of the rats in the TCM group were improved.The incidence of esophageal carcinogenesis of the TCM group was significantly lower compared with the model group(P<0.05).The results of serum bile acids showed that compared with the sham group in the same period,the taurocholic acid level was in-creased and the taurochenodeoxycholic acid and deoxycholic acid levels were decreased of the model group at 2 weeks after surgery(P<0.05);the tauroursodeoxycholic acid and taurodeoxycholic acid levels were increased at 4 weeks after surgery(P<0.05),and the taurocholic acid level increased at 8 weeks after surgery(P<0.05);compared with the model group at 8 weeks after surgery,the levels of glycocholic acid,taurocholic acid,taurochenodeoxycholic acid,and taurodeoxycholic acid decreased,but the difference has no statistical significant(P>0.05).And the cholic acid,deoxycholic acid,ursodeoxycholic acid,chenodeoxycholic acid,lithocholic acid,and taurolithocholic acid levels increased of the TCM group,but the difference has no statistical significant(P>0.05).Conclusion Ganwei Tongzhi TCM Compound has the effect of preventing and treating the carcinogenesis of esophagus caused by bile reflux,and can affect the metabolism of serum bile acids.

bile refluxhepatogastric therapybile acid metabolismreflux esophagitisbile reflux

顾杨怡、张笑、朱梅、崔金刚、徐亭亭、陈鑫、李黎

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200052 上海中医药大学附属光华医院上海市中医药研究院中西医结合关节炎研究所

上海中医药大学岳阳临床医学院

上海市中医药研究院中西医结合临床研究所

上海中医药大学附属岳阳中西医结合医院GCP办公室

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胆汁反流 肝胃同治 胆汁酸代谢 反流性食管炎 胆汁反流

上海市自然基金上海市卫生健康委员会临床专项国家自然基金青年基金项目长宁区卫生健康委员会临床专项

23ZR14538002019403648120281020214Z003

2024

环球中医药
中华国际医学交流基金会

环球中医药

CSTPCD
影响因子:1.553
ISSN:1674-1749
年,卷(期):2024.17(6)