AMP-18联合5-氨基水杨酸治疗大鼠结肠炎的效果

Effect of 5-aminosalicylic acid combined with antrum mucosal protein-18 on treatment of trinitrobenzene sulphonic acid induced colitis rats

  • 摘要: 目的:探讨联合应用 AMP-18皮下注射与5-氨基水杨酸(5-ASA)灌肠治疗对三硝基苯磺酸(TNBS)诱发的大鼠结肠炎髓过氧化物酶(MPO)、核因子(NF-kB)及表皮生长因子(EGF)表达的影响。方法选用雌雄各半健康 SD 大鼠40只,随机分为4组,每组10只。采用TNBS /乙醇灌肠制作大鼠结肠炎模型。制模后第2天,各组分别给予不同处理。A组给予0.9%氯化钠溶液1 mL 灌肠;B 组给予5-ASA 1 mL 灌肠(100 mg/kg);C 组给予 AMP-18用 pH 7.4的 PBS 配制,剂量10 mg/kg,皮下注射;D 组给予5-ASA 灌肠与 AMP-18注射联合处理。上述治疗均1次/d,观察大鼠腹泻及便血情况,并记录体质量改变。分别于治疗后第5、9天随机抽取每组大鼠各5只,按 DAI 的评分标准,进行大体损伤评分;按 Fedorak 积分标准,进行组织损伤评分,同时生化法检测髓过氧化物酶活性,免疫组化法分析 NF-kB 的组织表达;心脏取血,酶联免疫吸附实验测定血清 EGF的浓度。结果与 A 组比较,B、C、D 组 DAI 评分、大体损伤评分和组织学损伤评分及 MPO 活性均降低(P <0.05),NF-kB 表达水平降低(P <0.05),EGF表达水平明显升高(P <0.01),但B、C组间比较无显著差异(P >0.05)。联合应用rhITF与5-ASA 灌肠的效果优于单独应用和5-ASA (P <0.05)。结论联合应用 AMP-18与5-ASA 对 TNBS 诱发的大鼠结肠炎有良好的治疗作用,其疗效优于单独应用 AMP-18或5-ASA。其作用机制可能是通过降低肠组织中的 MPO 活性、抑制 NF-kB 表达与增强 EGF 表达。

     

    Abstract: Objective To explore the effect of 5-aminosalicylic acid (5-ASA)combined with antrum mucosal protein-18 (AMP-18)on the expression of myeloperoxidase (MPO),nuclear factor-kB(NF-kB)and epidermal growth factor (EGF)in trinitrobenzene sulphonic acid (TNBS)in-duced colitis rats.Methods 40 male sprague-dawley (SD)rats were randomly divided into group A,B,C and D.After the production of colitis,10 rats in each group were given the following topical treatments respectively:group A,normal saline;group B,5-ASA at the dose of 100 mg/kg;group C,AMP-18 at the dose of 10 mg/kg;group D,5-ASA and AMP-18.Animals were sacrificed at the 4th and 8th day after topical treatment.The macroscopic and histological changes of the colon were e-valuated and scored.MPO activity of the mucosa was detected by biochemical methods.Expressions of serum EGF and tissue NF-kB were detected by ELISA and immunohistochemistry respectively.Re-sults Compared with group A,macroscopic and histological scores and MPO activity in group B,C and D significantly decreased (P <0.05 ).Expressions of serum EGF were significantly higher in group B,C and D than in group A (P <0.01),while the expressions of tissue NF-kB significantly decreased (P <0 .0 5 ).The combination ofAMP -1 8 with 5 -ASA showed a better effect than single use of AMP -1 8 or 5 -ASA .Conclusion Topical treatment with 5 -ASA and AMP -1 8 shows a positive effect in treating TNBS-induced colitis rats,and combined treatment is better than single treatment.The mechanism is related to decreasing of content of colonic MPO,down-regulation of NF-kB and up-expression of EGF.

     

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