复方甘草酸苷抗大鼠溃疡性结肠炎作用机制的研究

Effect mechanism study of compound glycyrrhizin on ulcerative colitis in rats

目的观察复方甘草酸苷对溃疡性结肠炎(UC)模型大鼠的治疗作用,探讨其治疗UC的可能作用机制。方法将50只大鼠随机分成正常组(0.9%氯化钠溶液)、模型组(0.9%氯化钠溶液)、阳性对照组[300 mg/(kg.d)美沙拉嗪溶液]、复方甘草酸苷低剂量组[12.5 mg/(kg.d)]和复方甘草酸苷高剂量组[50 mg/(kg.d)]。除正常组外,其余大鼠采用2,4,6-三硝基苯磺酸法制备UC大鼠模型。造模3 d后,各组按设计剂量灌胃给药10 d,处死大鼠取结肠黏膜组织。进行病理检查及评分,测定丙二醛(MDA)、超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)的水平,并采用逆转录-聚合酶链反应法检测细胞间黏附因子-1(ICAM-1)基因表达变化。结果正常组、模型组、阳性对照组、复方甘草酸苷低剂量组和高剂量组病变评分依次为:(0.0±0.0)、(6.2±1.0)、(2.6±0.2)、(3.0±0.9)、(3.6±0.0)分;MDA含量依次为:(1.75±0.75)、(1.99±0.68)、(1.09±0.25)、(1.18±0.48)、(1.23±0.45)nmol/mgprot;SOD水平依次为:(97.19±13.27)、(85.25±24.88)、(70.00±12.61)、(65.19±24.51)、(78.03±19.77)U/mgprot;MPO水平依次为:(0.34±0.03)、(0.36±0.03)、(0.31±0.02)、(0.36±0.05)、(0.36±0.04)单位/克湿片;ICAM-1相对表达量依次为:(2.56±0.80)、(7.36±4.87)、(2.92±1.29)、(2.16±0.85)、(5.81±5.10)。与模型组相比,各治疗组结肠组织病变评分和MDA含量显著下降(P<0.05),SOD、MPO未见统计学差异。复方甘草酸苷低剂量组ICAM-1表达水平显著低于模型组(P<0.05),作用与阳性对照组相仿(P>0.05),但复方甘草酸苷高剂量组ICAM-1表达水平与模型组无显著变化(P>0.05)。结论复方甘草酸苷对UC有显著的治疗作用,机制可能与改善组织的病变程度,减轻或阻断组织的脂质过氧化反应,抑制结肠黏膜ICAM-1基因表达有关。

Objective To study the possible mechanism of compound glycyrrhizin on ulcerative colitis （UC） in Rats. Methods Fifty rats were divided into normal group （0.9% sodium chloride solution）, model group （0.9% sodium chlo- ride solution）, positive control group [300 mg]（kg.d） mesalazine solution], low-dose compound glycyrrhizin group [12.5 mg/（kg· d）] and high-dose compound glycyrrhizin group[50 mg（kg·d）]. Except the normal group, the other rats ulcera- tive colitis model were induced by 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）. After inducing model for 3 days, the rats were killed to get their colonic mucosa, according to each design dose to gavage after administration of 10 days. Histopathological score and the levels of malondialdehyde （MDA）, superoxide dismutase （SOD） and myeloperoxidase （MPO） were determined. Reverse transcription polymerase chain reaction （RT-PCR） was used to detect in-tercellular adhesion molecule 1 （ICAM-1） expressions. Results In the normal group, model group, positive control group, low- dose compound glycyrrhizin group and high-dose compound glycyrrhizin group,