CAJ | 학술논문

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。
목적：탐토연합응용 AMP-18피하주사여5-안기수양산（5-ASA）관장치료대삼초기분광산（TNBS）유발적대서결장염수과양화물매（MPO）、핵인자（NF-kB）급표피생장인자（EGF）표체적영향。방법선용자웅각반건강 SD 대서40지，수궤분위4조，매조10지。채용TNBS /을순관장제작대서결장염모형。제모후제2천，각조분별급여불동처리。A조급여0．9％록화납용액1 mL 관장；B 조급여5-ASA 1 mL 관장（100 mg/kg）；C 조급여 AMP-18용 pH 7．4적 PBS 배제，제량10 mg/kg，피하주사；D 조급여5-ASA 관장여 AMP-18주사연합처리。상술치료균1차/d，관찰대서복사급편혈정황，병기록체질량개변。분별우치료후제5、9천수궤추취매조대서각5지，안 DAI 적평분표준，진행대체손상평분；안 Fedorak 적분표준，진행조직손상평분，동시생화법검측수과양화물매활성，면역조화법분석 NF-kB 적조직표체；심장취혈，매련면역흡부실험측정혈청 EGF적농도。결과여 A 조비교，B、C、D 조 DAI 평분、대체손상평분화조직학손상평분급 MPO 활성균강저（P ＜0．05），NF-kB 표체수평강저（P ＜0．05），EGF표체수평명현승고（P ＜0．01），단B、C조간비교무현저차이（P ＞0．05）。연합응용rhITF여5-ASA 관장적효과우우단독응용화5-ASA （P ＜0．05）。결론연합응용 AMP-18여5-ASA 대 TNBS 유발적대서결장염유량호적치료작용，기료효우우단독응용 AMP-18혹5-ASA。기작용궤제가능시통과강저장조직중적 MPO 활성、억제 NF-kB 표체여증강 EGF 표체。
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.