甘草酸二铵对大鼠结肠炎的抗炎作用机制研究

Study on the anti-inflammatory mechanism of diammonium glycyrrhizinate in acetic acid-induced colitis of rats

目的建立大鼠急性期结肠炎模型,观察甘草酸二铵(DG)对大鼠结肠炎的治疗作用,并探讨其抗炎机制。方法雌性SD大鼠分为实验组、模型组和正常对照组,每组10只。实验组、模型组大鼠用冰乙酸灌肠建立急性期结肠炎模型,实验组给予40 mg.kg-1.d-1DG干预治疗。观察疾病活动指数(DAI)、组织学变化及髓过氧化物酶(MPO)活性,免疫组化法检测核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)和细胞间粘附分子-1(ICAM-1)表达。结果实验组、模型组和正常对照组的DAI评分分别为3.5±0.6,7.1±0.8和0.5±0.4;组织学评分为3.5±0.9,6.1±1.0和1.0±0.5;MPO活性为0.72±0.08,2.02±0.10和0.22±0.04;TNF-α阳性率分别为(35.2±8.2)%,(62.5±10.1)%和(7.9±5.7)%;ICAM-1阳性率为(34.3±8.2)%,(60.2±8.3)%和(9.1±3.4)%;NF-κB阳性率为(23.3±9.2)%,(44.5±8.9)%和(9.6±4.4)%。与模型组相比,实验组的DAI、组织学及MPO活性显著改善,实验组的TNF-αI、CAM-1和NF-κB的表达显著降低,经one-way ANOVA及SNK-q检验,差异有统计学意义(P值均<0.01)。结论DG可显著改善大鼠结肠炎症,其机制可能是通过影响炎症反应的信号通路NF-κB活化及ICAM-1、TNF-α的产生和表达来抑制炎症反应。

Objective To evaluate the role of diammonium glycyrrhizinate （DG） in experimental colitis and to probe into its underlying mechanisms. Methods Tirty female Spragur-Dawley rats were randomized into treatment group, acetic acid control and normal control groups （10 rats for each group）. Colitis in treatment group and acetic acid control was induced by administrating acetic acid rectally. The rats in treatment group were treated with DG. Disease activity index （DAD and histological damage as well as myeloperoxidase （MPO） activation were observed. The nuclear factor-~cB （NF-~cB） activity, the expression of tumor necrosis factor-α （TNF-α） and intercellular adhesion molecule-1 （ICAM-1） in colon tissues were detected by immunohistochemistry method. Results In treatment group, acetic acid control and normal control, the DAI were 3.5 ± 0.6, 7.1 ± 0.8 and 0.5 ± 0.4 respectively; the histological damage scores were 3.5±0.9, 6.1±1.0 and 1.0±0.5 respectively; MPO activation were 0.72±0. 08, 2.02±0. 10 and 0.22 ± 0. 04 respectively; the positive percentages of TNF-α were 35.2 ±8.2, 62.5±10. 1 and 7.9±5. 7 respectively, the positive percentages of ICAM-1 were 34.3±8.2,60. 2±8.3 and 9.1± 3.4 respectively; the positive percentages of NF-κB were 23.3 ± 9.2,44.5 ± 8.9 and 9.6 ± 4.4 respectively. Compared with the acetic acid control group, the DAI and histological damage scores as well as MPO activation of colon tissues in treatment group were significantly improved （P〈0.01）, and the expression of TNF-α, ICAM-1 and NF-κB in treatment group decreased significantly （P〈0.01）. Conclusions The present study indicates that DG can ameliorate the colonic inflammation. Suppressing NF-0642B activation and decreasing the expression of TNF-α and ICAM-1 in colon tissues may be the possible mechanism.