[关键词]
[摘要]
研究了鼠尾草酸(CA)对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的改善作用。小鼠自由饮用含3% DSS的蒸馏水,连续7 d造模。将60只小鼠随机分为5 组:空白对照组(CK)、DSS模型组(DSS)、鼠尾草酸低剂量组(CAL)、鼠尾草酸高剂量组(CAH)、美沙拉嗪组(PC)。通过小鼠体质量变化、疾病活动指数(DAI)评分、结肠组织病理学和肠道通透性变化评估CA对UC小鼠的干预作用。通过测定结肠组织髓过氧化物酶(MPO)活性、超过氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、紧密连接蛋白ZO-1和Occludin的表达及肠道菌群组成的变化探讨可能的影响机制。与DSS组相比,CA干预降低了UC小鼠的质量损失和DAI评分、改善了结肠组织病理损伤。同时,CAL和CAH组结肠组织MPO活性显著降低、MDA含量分别降低了13.75%、70.00%(P<0.05),SOD 活性分别升高了6.12倍、9.62倍(P<0.05),肠道通透性显著降低、ZO-1和Occludin蛋白的表达得到恢复。50 mg/kg mb的CA灌胃提高了厚壁菌门和拟杆菌门的丰度比值,恢复了DSS诱导的UC小鼠中Akkermansia等有益菌属的丰度下降,降低了Alistipes等有害菌属的相对丰度。CA对UC具有良好的改善作用,其机制可能与降低氧化应激水平、保护肠屏障和调控肠道微生物组成有关。
[Key word]
[Abstract]
The ameliorative effects of carnosic acid (CA) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice were assessed. Ulcerative colitis was induced by the oral administration of 3% DSS via distilled drinking water for seven days. A total of 60 mice were randomly divided into five groups: blank control (CK), DSS model (DSS), low-dose carnosic acid (CAL), high-dose carnosic acid (CAH), and mesalazine (PC). The ameliorative effects of CA were evaluated based on body weight, disease activity index (DAI) score, colonic histopathology, and changes in intestinal permeability. To investigate the possible mechanism of CA, the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), the level of malondialdehyde (MDA), the expression level of tight junction proteins, including ZO-1 and occludin, and the changes in intestinal flora in mice were examined. When the CA and DSS groups were compared, CA intervention was found to reduce weight loss and the DAI score and ameliorate the pathological damage in colonic tissues in UC mice. The MPO activity was also found to significantly decrease in the CA groups. The MDA content in the colon tissue was reduced by 13.75% and 70%, respectively (P<0.05), while the SOD activity increased by 6.12- and 9.62-fold, respectively (P<0.05), in the CAL and CAH groups. Notably, the intestinal permeability was significantly reduced, and the expression levels of ZO-1 and occludin were restored. Gavage of 50 mg/kg CA enhanced the abundance ratios of Firmicutes and Bacteroides and restored the decrease in the abundance of beneficial bacteria, such as Akkermansia, caused by DSS. The relative abundance of detrimental bacteria, such as Alistipes, was also reduced. Overall, CA may mitigate UC by lowering the levels of oxidative stress, protecting the intestinal barrier, and regulating the composition of the intestinal microbial community.
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[基金项目]
北京市自然科学基金资助项目(6212002);北京市教委一般项目(KM202010011010)