姜婷婷 江宇泳 叶永安

摘要 目的：探讨健脾解毒凉血方治疗肝损伤肠屏障功能障碍的作用靶点。方法：选取C57BL/6雄性小鼠32只，随机分为正常组、模型组、中药组、培菲康组，腹腔注射硫代乙酰胺100 mg/kg造模;中药组予以健脾解毒凉血方灌胃，培菲康组给予培菲康溶液灌胃;16 h后采集小鼠血清、肝组织、小肠组织，观察小鼠肝功能、肠道组织HE染色变化，免疫组织化学染色方法观察小肠闭锁小带蛋白-1表达。结果：模型组、中药组、培菲康组小鼠的ALT、AST均显著高于正常组，模型组、中药组、培菲康组比较差异无统计学意义（P>0.05）。小肠组织在光镜和电镜下均可观察到中药组病变轻于模型组和培菲康组，免疫组织化学染色在小肠上皮细胞上可见闭锁小带蛋白-1棕黄色阳性标记，模型组、中药组、培菲康组阳性标记均显著少于正常组，中药组阳性标记显著多于模型组（P<0.05）。结论：健脾解毒凉血方治疗硫代乙酰胺诱导急性肝损伤小鼠，可维护肠上皮细胞紧密连接部闭锁小带蛋白-1表达，修复肠屏障功能。

关键词 健脾解毒凉血方;硫代乙酰胺，肝损伤;肠屏障功能;闭锁小带蛋白-1;紧密连接蛋白;小鼠;肠道

Abstract Objective：To explore the target of Jianpi Jiedu Liangxue Formula in the treatment of intestinal barrier dysfunction in liver injury.Methods：A total of 32 male C57BL/6 mice were randomly divided into a normal group，a model group，a Chinese medicine group and a Peifikang group.Mouse liver injury model by intraperitoneal inject of thioacetamide 100 mg/kg was established.The mice in the traditional Chinese medicine group were given Jianpi Jiedu Liangxue Formula for gavage.The mice in the Peficon Kang group were given Pefikang solution.After16 hours，mice serum，liver tissue，and small intestinal tissue were collected.Liver function，intestinal HE histochemical changes，immunohistochemical staining method were observed the expression of ZO-1 protein in the small intestine.Results：The ALT and AST of the model group，the Chinese medicine group and the Peifikang group were significantly higher than those of the normal group（P>0.05）.There was no significant difference between the model group，the Chinese medicine group and the Peifikang group.Small intestinal tissue can be observed under light and electron microscopy.Immunohistochemical staining in the cell membrane of intestinal villus epithelial cells were visible on the zonula occludens protein-1 Brown positive marker.The positive markers of model group，Chinese medicine group and Peifikang group were significantly less than which of normal group.The positive marker of Chinese medicine group were significantly more than that of model group（P<0.05）.Conclusion：Jianpi Jiedu Liangxue Formula in the treatment of acute liver injury induced by thioacetamide can maintain the expression of zonula occludens protein-1 in the tight junction of intestinal epithelial cells and repair intestinal barrier function.

Keywords Jianpi Huashi Jiedu Formula; Thioacetamide; Liver injury; Small intestinal barrier function; Zonula occludens protein-1; Tight junction protein; Mice; Intestinal

中圖分类号：R289.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.07.012

重症肝病时肠道缺血、缺氧、循环障碍，肠黏膜淤血、水肿、糜烂，通透性增加;肠屏障功能受损导致大量内毒素经门静脉进入肝脏，其诱导的一系列炎症反应加剧了肝损伤，并与自发性细菌性腹膜炎等并发症密切相关[1-2]。在“见肝之病，知肝传脾，当先实脾”的中医经典理论指导下，我们以健脾化湿解毒法治疗重症肝病合并肠功能障碍取得较好的临床效果。为探索中医药修复肝损伤并发肠屏障……