黄芩素对葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠的改善作用

Protective effect of baicalein on mice with ulcerative colitis induced by dextran sulfate sodium salt

目的:探究黄芩素(baicalein)对葡聚糖硫酸钠(dextran sulfate sodium salt, DSS)诱导的溃疡性结肠炎(ulcerative colitis, UC)小鼠的疗效及可能的作用机制。方法:将42只雄性BALB/c小鼠随机分为6组(n=7),分别为空白组,模型组,黄芩素低、中、高剂量组和美沙拉嗪阳性药物对照组。采用4%的DSS创建小鼠UC模型,造模成功后,空白组和模型组自由饮用蒸馏水,黄芩素低、中、高剂量组分别灌胃(ig)10,20,40 mg·kg^(-1)黄芩素混悬液,阳性药物组给予美沙拉嗪600 mg·kg^(-1),ig,连续治疗14 d。计算并评价疾病活动指数(DAI);采用苏木精-伊红染色法(HE)观察小鼠结肠组织病理学变化;采用酶联免疫吸附测定(ELISA)试剂盒定量检测血清中脂多糖(LPS)、分泌型免疫球蛋白A(sIg A)水平;采用蛋白免疫印迹法(Western blot)检测各组小鼠结肠组织中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和核转录因子-κB(NF-κB)的表达。结果:黄芩素可降低UC小鼠DAI指数,降低结肠组织中IL-6,TNF-α,NF-κB蛋白表达,降低血清中LPS水平,提高血清中sIg A的含量。结论:黄芩素可通过降低炎性反应、增强机体免疫,对UC小鼠发挥疗效,其作用机制与调节结肠NF-κB的表达有关。

Objective: to investigate the therapeutic effect and possible mechanism of baicalein on ulcerative colitis induced by dextran sulfate sodium salt(DSS) in mice. Methods: A total of 42 male BALB/c mice were randomly divided into 6 groups(n=7), including control group, model group, baicalein groups(low-dose, medium-dose and high-dose) and mesalazine group(positive). The UC model of mice was established by 4% DSS. After the model was successfully established, the control group and the model group were given distilled water ad libitum, baicalein suspension of 10, 20, and 40 mg·kg^(-1), and the positive drug mesalazine 600 mg·kg^(-1), ig, for 14 days. The disease activity index(DAI) was calculated and evaluated, the changes of colon histopathology were observed by hematoxylin-eosin(HE) staining, and the levels of lipopolysaccharide(LPS) and secretory immunoglobulin A(sIg A) in serum were measured by ELISA. The expression levels of interleukin-6(IL-6), tumor necrosis factor α(TNF-α) and nuclear factor of activated B(NF-κB) were detected by Western blotting. Results: Baicalein decreased DAI index of UC mice, decreased the protein expressions of IL-6, TNF-α and NF-κB in colon tissue, decreased the serum levels of LPS, and increased the content of sIg A in serum. Conclusion: Baicalein reduced the inflammatory response and enhanced the immunity of UC mice, and the mechanism is related to regulating the expression of NF-κB in colon.