黄立权 张志荣 江荣林 王坤根

〔摘要〕 目的 觀察四君子汤对气虚型急性胃肠功能损伤小鼠小肠Cajal间质细胞（interstitial cells of Cajal， ICC）及黏膜上皮跨膜蛋白claudin-2、occludin表达的影响。方法 将48只ICR小鼠随机分为正常组（n=12）和实验组（n=36），实验组制备成标准气虚型急性胃肠功能损伤小鼠模型，再随机分为模型组、四君子汤组、自愈组，每组12只。正常组和模型组小鼠于造模成功后处死;四君子汤组小鼠给予四君子汤灌胃，自愈组小鼠等量生理盐水灌胃，每天1次，连续灌胃7 d，禁食不禁水12 h后处死。留取各组距离回盲部2 cm的小肠组织，行HE染色和免疫组化，观察小鼠肠道ICC中c-kit及肠黏膜上皮跨膜蛋白claudin-2、occludin表达的变化。结果 HE染色显示四君子汤治疗后小鼠肠黏膜损伤明显改善;免疫组化显示：与正常组比较，造模后实验组各组c-kit及跨膜蛋白claudin-2、occludin表达明显下降（P<0.01）。与模型组比较，四君子汤组和自愈组c-kit及肠黏膜上皮跨膜蛋白claudin-2、occludin表达明显上升（P<0.01）;与自愈组比较，四君子汤组c-kit及肠黏膜上皮跨膜蛋白claudin-2、occludin表达明显上升（P<0.01）。结论 四君子汤可通过增加c-kit、claudin-2、occludin的表达改善肠道黏膜通透性和肠动力，以治疗气虚型急性胃肠功能损伤。

〔关键词〕 急性胃肠功能损伤;动物模型;跨膜蛋白;气虚型;四君子汤

〔中图分类号〕R285.5       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2020.06.008

〔Abstract〕 Objective To observe the effect of Sijunzi Decoction on the expression of interstitial cells of Cajal （ICC） and intestinal mucosal epithelial transmembrane proteins claudin-2， occludin in acute gastrointestinal impairment mouse of Qi-deficiency. Methods A total of 48 ICR mice were randomly divided into a normal group （n=12） and an experimental group （n=36）. The experimental group was prepared into a standard acute gastrointestinal impairment mouse animal model of Qi-deficiency， and then randomly divided into a model group， a Sijunzi Decoction group， and a self-healing group （n=12 in each group）. The mice in the normal group and the model group were sacrificed after successfully modeling. Mice in the Sijunzi Decoction group were treated by gavage with Sijunzi Decoction， and mice in the self-healing group were given the equal saline， once a day， for continuous 7 days. They were killed after 12 days fasting food but not water. The small intestine tissue 2 cm away from ileocecum were retained. Then HE staining and immunohistochemistry were performed to observe the changes of c-kit in intestinal ICC and intestinal mucosal epithelial transmembrane proteins claudin-2 and occludin in mice. Results HE staining showed that the intestinal mucosal damage was obviously improved in mice after Sijunzi Decoction treatment. Immunohistochemistry showed that compared with the normal group， the expressions of c-kit and transmembrane proteins claudin-2 and occludin in the experimental group was significantly decreased after modeling （P<0.01）. Compared with the model group， the expressions of c-kit and intestinal mucosal epithelial transmembrane proteins claudin-2 and occludin in the Sijunzi Decoction group and self-healing group were significantly increased （P<0.01）. Compared with the self-healing group， the expression of c-kit and intestinal mucosal epithelial transmembrane proteins claudin-2 and occludin in the Sijunzi Decoction group were significantly increased （P<0.01）. Conclusion Sijunzi Decoction could increase the expression of c-kit， claudin-2 and occludin to improve the intestinal mucosa permeability and intestinal motility， and has a therapeutic effect on mice with acute gastrointestinal impairment of Qi-deficiency.

〔Keywords〕 acute gastrointestinal impairment; animal model; transmembrane protein; Qi-deficiency syndrome; Sijunzi Decoction

急性胃肠功能损伤（acute gastrointestinal function injury， AGI）是危重病患者的常见并发症，是常继发于创伤、烧伤、休克和其他全身性病变的一种胃肠道急性病理改变，以胃肠道黏膜损害以及运动和屏障功能障碍为主要特点。本病不是一组独立的疾病，而是多器官功能障碍（multiple organ dysfunction syndrome， MODS）的一部分，可导致喂养不耐受、胃潴留、呕吐、腹泻、消化道出血、麻痹性肠梗阻及腹内高压甚至引发腹腔间隔室综合征等。2012年，欧洲危重病学会对AGI重新作了定义和分级[1]，有文献指出其在ICU的发病率达62%以上[2]，临床上如果不及时处理，此类危重症患者往往进展成多脏器功能衰竭，死亡率将大幅上升[3]。……