目的 研究首荟通便胶囊对慢性传输性便秘小鼠肠道屏障的影响。方法 48只ICR小鼠随机分成对照组、模型组和首荟通便胶囊（300 mg/kg）组，小鼠ig复方地芬诺酯（10 mg/kg）建立便秘模型，同时给予药物进行干预。实验结束后，检测小鼠肠蠕动和排便功能，采用ELISA法检测小鼠血清肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和D-乳酸水平；采用苏木素-伊红（HE）染色法考察小鼠结肠组织病理变化；采用Western blotting检测小鼠结肠组织紧密连接蛋白-1（zonula occludens-1，ZO-1）、Occludin、Claudin 5、基质金属蛋白酶-9（matrix metalloprotein-9，MMP-9）、MMP-2和金属蛋白酶组织抑制因子-1（tissue inhibitor of metalloproteinase-1，TIMP-1）的蛋白表达情况。结果 与对照组相比，模型组小鼠排便功能和肠蠕动功能降低（P＜0.05、0.01），肠道炎性细胞浸润明显；血清中D-乳酸和TNF-α水平显著升高（P＜0.05、0.01）；结肠组织Claudin 5、Occludin、ZO-1和TIMP-1蛋白表达水平降低（P＜0.05、0.01），MMP-2和MMP-9蛋白表达水平升高（P＜0.05）。与模型组相比，首荟通便胶囊组小鼠排便功能和肠蠕动功能增强（P＜0.05、0.01），肠道炎性细胞浸润减少；血清中D-乳酸和TNF-α水平降低（P＜0.05）；结肠组织Claudin 5、Occludin、ZO-1和TIMP-1蛋白表达水平升高（P＜0.05、0.01），MMP-2和MMP-9蛋白表达水平降低（P＜0.05）。结论 首荟通便胶囊能够治疗小鼠便秘，其机制可能与降低便秘小鼠肠道炎症和通透性、调节肠道屏障相关蛋白的表达以及保护肠道屏障有关。

Objective To study the effect of Shouhui Tongbian Capsules (首荟通便胶囊) on intestinal barrier of mice with chronic transitive constipation. Methods Forty-eight mice were randomly divided into control group, model group and Shouhui Tongbian Capsules (300 mg/kg) group, constipation model was established by ig compound diphenoxylate (10 mg/kg), at the same time, drugs were given for intervention. After the experiment, bowel motility and defecation function of mice were detected, tumor necrosis factor-α (TNF-α) and D-lactic acid levels in serum were detected by ELISA; Pathological changes of colon tissue in mice were observed by HE; Western blotting was used to detect the protein expressions of zonula occludens-1 (ZO-1), Occludin, Claudin 5, matrix metalloprotein-9 (MMP-9), MMP-2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in colon tissue of mice. Results Compared with control group, defecation function and bowel motility function of mice in model group were reduced (P < 0.05, 0.01), infiltration of intestinal inflammatory cells was obvious; D-lactic acid and TNF-α levels in serum were increased (P < 0.05, 0.01); Claudin5, Occludin, ZO-1 and TIMP-1 protein expressions in colon tissue were decreased (P < 0.05, 0.01), MMP-2 and MMP-9 protein expressions were increased (P < 0.05). Compared with model group, bowel function and bowel motility function of mice in Shouhui Tongbian Capsules group were increased (P < 0.05, 0.01), inflammatory infiltration of intestinal tissue cells was decreased; D-lactic acid and TNF-α levels in serum were decreased (P < 0.05); Claudin5, Occludin, ZO-1 and TIMP-1 protein expressions in colon tissue were increased (P < 0.05, 0.01), MMP-2 and MMP-9 protein expressions were decreased (P < 0.05). Conclusion Shouhui Tongbian Capsules can treat constipation in mice, its mechanism may be related to reducing intestinal inflammation and permeability, regulating the expression of intestinal barrier-related proteins and protecting the intestinal barrier.

R285.5

国家“重大新药创制”科技重大专项（2018ZX09201010）