盐酸小檗碱增强美沙拉嗪在治疗溃疡性结肠炎中的作用机制

Berberine hydrochloride enhances the effect of mesalazine on the treatment of ulcerative colitis

目的探讨盐酸小檗碱辅助治疗溃疡性结肠炎(UC)的疗效及其作用机制。方法将SD大鼠分为5组(n=8),正常对照组大鼠予自由饮用蒸馏水,其余4组予自由饮用蒸馏水配置的浓度为5.5%的葡聚糖硫酸钠(DSS)溶液,连续7 d,形成UC大鼠模型。第8～14天,美沙拉嗪组、盐酸小檗碱组分别予美沙拉嗪(420 mg/kg)、盐酸小檗碱(100 mg/kg)灌胃,盐酸小檗碱联合美沙拉嗪组予盐酸小檗碱(100 mg/kg)及美沙拉嗪(420 mg/kg)联合灌胃。观察5组大鼠的疾病活动度(DAI评分)以及各组大鼠结肠组织病理学变化,酶联免疫吸附测定试验检测大鼠血清IL-9表达量,逆转录聚合酶链反应方法及免疫组织化学法分别检测大鼠结肠组织中TLR2 mRNA、TLR2蛋白的表达水平。结果 (1)与正常对照组比较,DSS模型组DAI评分、结肠组织病理学评分、IL-9、TLR2 mRNA、TLR2蛋白表达明显升高(P<0.01)。(2)与DSS模型组对比,美沙拉嗪组、盐酸小檗碱组、盐酸小檗碱联合美沙拉嗪组第14天DAI评分、结肠组织病理学评分、血清IL-9、结肠组织TLR2 mRNA、TLR2蛋白表达均下降(P<0.05),且盐酸小檗碱联合美沙拉嗪组下降更明显(P<0.01)。结论盐酸小檗碱可能通过降低IL-9水平以及TLR2 mRNA、TLR2蛋白的表达增强美沙拉嗪治疗UC的作用。

Objective To investigate the effect and mechanism of berberine hydrochloride in the adjuvant treatment of ulcerative colitis(UC).Methods Forty rats were divided into 5 groups(n=8).The normal control group was with given distilled water,while dextran sulfate sodium(DSS)were given in the other 4 groups for the construction of UC model.After modeling,normal control group and DSS model group were given by gavage of distilled water,while mesalazine(420 mg/kg),berberine hydrochloride(100 mg/kg),and berberine hydrochloride(100 mg/kg)combined with mesalazine(420 mg/kg),were given to rats in mesalazine group,berberine hydrochloride,and berberine hydrochloride combined with mesalazine group,respectively.The degree of disease activity(DAI score)and the pathological changes of colon tissue were compared.The serum IL-9 were measured by enzyme linked immunosorbent assay,and the reverse transcription polymerase chain reaction and immunohistochemistry were used to assess the expression levels of TLR2 mRNA and TLR2 protein in rat colon tissues.Results Compared with the normal control group,the DAI score,the colonic histopathology score,IL-9,TLR2 mRNA and TLR2 protein expression in the DSS model group were significantly higher(P<0.01).Compared with the DSS model group,the DAI score,the colonic histopathology score,IL-9,TLR2 mRNA and TLR2 protein expression of mesalazine group,berberine hydrochloride group and berberine hydrochloride combined with mesalazine group were significantly reduced(P<0.05);which were significantly more prominent in berberine hydrochloride combined with mesalazine group(P<0.01).Conclusion Berberine hydrochloride may enhance the effect of methalazine in the treatment of ulcerative colitis by reducing the level of IL-9 and the expression of TLR2 mRNA and TLR2 protein.