槲皮素与5-氨基水杨酸协同治疗感染后肠易激综合征大鼠的药效机制

目的：研究槲皮素与5-氨基水杨酸（5-ASA）对感染后肠易激综合征（PI-IBS）的治疗作用及其机制。方法：PI-IBS大鼠模型分别灌胃给予5-ASA、槲皮素或5-ASA联合槲皮素，连续给药2周。腹壁收缩实验测定内脏痛阈值，水应激法评价结肠运动；收集血液和结肠，液质联用法测定5-ASA及其代谢物N-乙酰-5-ASA含量。结果：与正常组相比，PI-IBS组内脏痛阈值显著降低，结肠排便增多（P<0.05）。与模型组相比，5-ASA联合槲皮素可显著提高PI-IBS大鼠内脏痛阈值并明显减少结肠排便数量，其作用优于各单独用药组。槲皮素可明显增加PI-IBS大鼠结肠5-ASA含量并显著降低N-乙酰-5-ASA含量（P<0.05）。结论：槲皮素联合5-ASA对PI-IBS大鼠具有协同治疗作用，其机制可能与槲皮素抑制5-ASA代谢酶，提高结肠5-ASA浓度从而增强其治疗效果有关。

Synergistic effects and underlying mechanism of quercetin and 5-aminosalicylic acid on post-infactious irritable bowel syndrome in rats

OBJECTIVE To investigate therapeutic effects and mechanism of quercetin and 5-aminosalicylic acid (5-ASA) on post-infectious irritable bowel syndrome (PI-IBS) in rats.METHODS PI-IBS rats were orally administered 5-ASA, quercetin or 5-ASA plus quercetin, respectively. Drugs were given to rats for 2 weeks consecutively. After treatment, visceral pain threshold pressure was measured by abdominal withdrawal reflex test, while colonic transit was evaluated by water avoidance stress test in PI-IBS rats. Then blood samples and colon tissues were collected for determination of concentrations of 5-ASA and its metabolite N-acetyl-5-ASA (N-AC-5-ASA) by LC-MS/MS method.RESULTS Compared to normal rats, PI-IBS rats presented significantly reduced visceral pain threshold pressure and increased fecal pellet output (P<0.05). Compared to PI-IBS model rats, pain threshold pressure was markedly increased, while fecal pellet output was significantly reduced in rats treated with 5-ASA in combination with quercetin, and this therapeutic effect was superior to that of rats treated with 5-ASA or quercetin only. Moreover, quercetin treatment significantly increased content of 5-ASA but markedly reduced content of N-AC-5-ASA in colon tissues of PI-IBS rats (P<0.05).CONCLUSION Synergistic therapeutic effects are observed in PI-IBS rats treated with 5-ASA in combination with quercetin, and underlying mechanism may be correlated with inhibitory effects of quercetin on 5-ASA metabolic enzyme, which increases colonic concentration of 5-ASA, and thus improves therapeutic effects of 5-ASA in PI-IBS rats.