CAJ | 학술논문

目的探讨炎性反应程度对小鼠炎性肠病(IBD)癌变的作用及其机制.方法联合运用致癌剂氧化偶氮甲烷(AOM)和致炎剂硫酸葡聚糖钠(DSS)于36只C57BL/6J雌性小鼠,构建IBD癌变的动物模型,通过改变DSS的浓度,构建不同炎性反应程度的动物模型,即低炎性反应组(1％ DSS,12只)、高炎性反应组(2％DSS,12只)及对照组(无DSS,正常饮用水,12只),通过计算3组小鼠的疾病活动指数(DAI)及炎性反应评分来评估炎性反应程度,通过实时定量PCR来检测小鼠结肠组织炎性因子mRNA的表达水平,通过免疫组织化学(免疫组化)来检测STAT3信号通路在不同炎性反应组织中的差异性表达,同时观察小鼠成瘤情况.结果高炎性反应组DAI评分和组织学炎性反应评分均较低炎性反应组显著升高(均P＜0.05),而对照组未见组织学炎性反应.高炎性反应组小鼠的结肠组织炎性因子的mRNA表达水平较低炎性反应组和对照组明显升高(均P＜0.05).高炎性反应组较低炎性反应组成瘤率[100％(12/12)比58.3％ (7/12)]、成瘤数目[(12.5±0.5)个比(6.6±1.0)个]及肿瘤负荷[(44.2±2.4) mm比(18.7±2.7) mm]均显著增加(均P＜0.05),而对照组未见肿瘤形成.p-STAT3 (Tyr705)在低炎性反应组中的表达的免疫组化评分为(3.67±0.19)分,明显低于高炎性反应组的(4.33±0.22)分(P=0.033).结论炎性反应可以促进IBD癌变,这可能与STAT3信号通路的激活有关.
목적 탐토염성반응정도대소서염성장병(IBD)암변적작용급기궤제.방법 연합운용치암제양화우담갑완(AOM)화치염제류산포취당납(DSS)우36지C57BL/6J자성소서,구건IBD암변적동물모형,통과개변DSS적농도,구건불동염성반응정도적동물모형,즉저염성반응조(1％ DSS,12지)、고염성반응조(2％DSS,12지)급대조조(무DSS,정상음용수,12지),통과계산3조소서적질병활동지수(DAI)급염성반응평분래평고염성반응정도,통과실시정량PCR래검측소서결장조직염성인자mRNA적표체수평,통과면역조직화학(면역조화)래검측STAT3신호통로재불동염성반응조직중적차이성표체,동시관찰소서성류정황.결과 고염성반응조DAI평분화조직학염성반응평분균교저염성반응조현저승고(균P＜0.05),이대조조미견조직학염성반응.고염성반응조소서적결장조직염성인자적mRNA표체수평교저염성반응조화대조조명현승고(균P＜0.05).고염성반응조교저염성반응조성류솔[100％(12/12)비58.3％ (7/12)]、성류수목[(12.5±0.5)개비(6.6±1.0)개]급종류부하[(44.2±2.4) mm비(18.7±2.7) mm]균현저증가(균P＜0.05),이대조조미견종류형성.p-STAT3 (Tyr705)재저염성반응조중적표체적면역조화평분위(3.67±0.19)분,명현저우고염성반응조적(4.33±0.22)분(P=0.033).결론 염성반응가이촉진IBD암변,저가능여STAT3신호통로적격활유관.
Objective To confirm that the severity of inflammation can promote the colitisassociated colorectal cancer(CAC) and explore the function of STAT3 signal pathway in CAC.Methods Mutagenic agent azoxymethane (AOM) and pro-inflammatory agent dextran sodium sulfate salt (DSS) were used to develop a mouse model of CAC.By changing the concentration of DSS (0,1％ and 2％ respectively),the mouse model with different extent of severity of inflammation was developed and the risk of carcinogenesis among these groups was compared.The expression of STAT3 signal pathway was detected by immunohistochemistry staining.Results In the evaluation of inflammatory severity,disease activity index,histopathological inflammation scores and the expression of pro-inflammation chemokines such as TNF-α,IL-6 and IL-12 in the higher inflammatory response group were higher than that in the lower inflammatory response group.The incidence of colorectal tumor was 100％ (12/12) in the higher inflammatory response group and the incidence of colorectal tumor was 58.3％ (7/12) in the lower inflammatory response group,and the difference between these two group was statistically significant (P＜0.05).The multiplicity(number of tumors/colon) was 12.5±0.5 in the higher inflammatory response group and the multiplicity was 6.6±1.0 in the lower inflammatory response group,and the difference between these two groups was statistically significant(P＜0.001).The tumor load(sum of tumor diameters per mouse) in the higher inflammatory response group was 44.2 ±2.4 mm and that in the lower inflammatory response group was only 18.7±2.7 mm,and the difference between these two groups was statistically significant(P＜0.0001).Moreover,the expression of p-STAT3 (Tyr705) was higher in colitis tissue of the higher inflammatory response group than that of the lower inflammatory response group.Conclusions Inflammation can promote the colitis-associated CAC.And the activation of STAT3 signal pathway may promote the development of CAC.