中药复方长安Ⅱ号修复炎症后肠易激综合征大鼠的肠黏膜屏障。
Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome.
作者信息
Wang Feng-yun, Su Min, Zheng Yong-qiu, Wang Xiao-ge, Kang Nan, Chen Ting, Zhu En-lin, Bian Zhao-xiang, Tang Xu-dong
机构信息
Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Xuanwu Traditional Chinese Medical Hospital, Beijing 100000, China.
出版信息
Acta Pharmacol Sin. 2015 Jun;36(6):708-15. doi: 10.1038/aps.2014.170. Epub 2015 May 11.
AIM
The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model.
METHODS
A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier.
RESULTS
PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4.
CONCLUSION
Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.
目的
中药复方长安Ⅱ号源自经典中医方剂痛泻要方，用于治疗肠易激综合征（IBS）的肝郁脾虚证。本研究在大鼠炎症后肠易激综合征（PI-IBS）模型中探讨长安Ⅱ号对肠黏膜免疫屏障的影响。
方法
采用多刺激范式建立PI-IBS大鼠模型，包括出生后早期同窝幼崽剥夺、束缚及直肠内注射三硝基苯磺酸（TNBS）。TNBS注射4周后，大鼠接受长安Ⅱ号（2.85、5.71和11.42 g·kg⁻¹·d⁻¹，灌胃）治疗14天。基于腹部回撤反射（AWR）评分和粪便含水量评估肠道敏感性。采用旷场试验和双瓶蔗糖摄取试验评估行为变化。计数肠黏膜中的CD4⁺和CD8⁺细胞，并检测IL-1β和IL-4水平。采用透射电子显微镜评估肠黏膜屏障的超微结构变化。
结果
PI-IBS模型大鼠的AWR反应性和粪便含水量显著增加，运动活性和蔗糖摄取减少。长安Ⅱ号治疗不仅降低了AWR反应性和粪便含水量，还抑制了焦虑和抑郁行为。超微结构研究显示，PI-IBS模型大鼠的肠道黏膜屏障功能严重受损，而长安Ⅱ号治疗减轻了肠黏膜炎症并修复了肠道黏膜屏障。此外，PI-IBS模型大鼠固有层和黏膜下层的CD4⁺/CD8⁺细胞比值显著降低，肠黏膜中IL-1β表达增加而IL-4表达减少，而长安Ⅱ号治疗逆转了PI-IBS诱导的CD4⁺/CD8⁺细胞比值及IL-1β和IL-4表达的变化。
结论
长安Ⅱ号通过抗炎、免疫调节和抗焦虑作用保护肠黏膜免受PI-IBS的影响。
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