柠檬苦素对葡聚糖硫酸钠诱导的小鼠结肠炎的治疗作用及机制

Therapeutic effect and mechanism of limonin on dextran sulfate sodium salt-induced ulcerative colitis in mice

探讨柠檬苦素(limonin)对葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)致实验性小鼠溃疡性结肠炎(ulcerative colitis,UC)模型的治疗作用及其机制。将20只8周龄雌性C57BL/6J小鼠,随机分为正常对照组、模型组、柠檬苦素组和5-氨基水杨酸组,每组5只。正常的小鼠每日给予蒸馏水饮用,其余各组小鼠给予30 g/L DSS连续饮用7 d后,继续饮用正常水3 d,诱导小鼠急性UC模型。药物治疗组小鼠分别灌胃给予柠檬苦素和5-氨基水杨酸的剂量为50和50 mg/(kg·d),每日1次,连续灌胃治疗10 d。实验终点时,分析实验动物的体质量变化、结肠长度、结肠组织病理学变化及细胞核转录因子kappa B (NF-κB)的蛋白表达。结果发现:与模型组比较,柠檬苦素可显著改善DSS诱导的小鼠急性结肠炎症状,包括体质量降低、结肠长度缩短、稀便和血便等,减轻小鼠急性结肠炎结肠组织的病理损伤,抑制炎症细胞的浸润和肠黏膜坏死。此外,柠檬苦素亦可以降低结肠炎小鼠结肠组织细胞核内NF-κB p65蛋白表达,抑制NF-κB p65的激活。柠檬苦素通过抑制NF-κB p65的激活,缓解DSS诱导的小鼠结肠炎症,发挥治疗作用。

To investigate the therapeutic effect and mechanism of limonin （ LIM） on dextran sulfatesodium salt （ DSS）.induced ulcerative colitis （ UC） in mice. Twenty C57BL / 6J mice were randomlydivided into the control group,model group,limonin group and 5.ASA group with 5 mice in each group.The control group mice were fed with distilled water,and the other groups mice were provided 30 g / L DSSto induce the acute UC model.At the beginning of the day of drinking DSS,50 mg / （kg·d） limonin and 50 mg / （ kg·d） 5.ASA were given to the mice of treatment groups respectively through intragastricadministration for 10 d.The body weight,colon length and the tissue pathology of the mice were analyzedat the end of experiments colitis in mice,and the protein expression of nuclear factor （NF.κB p65） wasobserved and compared.Compared with the model group,limonin improved the syndromes of colitis mice.Limonin attenuated DSS.induced body weight loss, colon length shortening, diarrhea and intestinalbleeding.Haematoxylin ＆ eosin （H＆E） staining assay showed that limonin alleviated colonic pathologicaldamage of colitis mice,remarkably inhibited inflammatory cells infiltration and intestinal mucosal necrosis.Moreover,limonin significantly inhibited the nuclear translocation and activation of NF.κB p65 in colontissues of colitis mice.Limonin could attenuate clinical syndromes of colitis and inhibit the inflammation ofcolitis by inhibiting the nuclear translocation and activation of NF.κB p65.