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目的考察雷帕霉素对克罗恩病小鼠模型的治疗作用及相关机制研究。方法 30只小鼠,采用随机数字表法分为3组:M1组(正常对照组,n=10),M2组(TNBS造模组,n=10),M3组(TNBS+雷帕霉素治疗组,n=10)。M1组以生理盐水灌肠予以对照;M2组建立克罗恩小鼠疾病模型,以生理盐水腹腔注射;M3组建立克罗恩小鼠疾病模型,并给予雷帕霉素腹腔注射。各组于造模后7d取小鼠结肠切片后行HE染色,并取病灶结肠组织和心脏取血,提取RNA反转录并进行PCR,检测Tim-1、Tim-3、Foxp3的基因表达情况,了解各指标之间的关联性。结果成功构建小鼠的CD模型,M3组相较M2组,病理学评分较低,病情较轻,各组间差异有统计学意义(P<0.05)。结肠组织和外周血中:Tim-1mRNA各组比较,差异无统计学意义(P>0.05)。Tim-3mRNA,Foxp3mRNA各组比较,差异有统计学意义(P<0.05)。结肠组织中还发现Tim-3mRNA表达量与Foxp3mRNA表达量呈负相关(r=-1.6275,P<0.05)。结论雷帕霉素可通过促进调节性T细胞分化,增加Foxp3表达量,来抑制Tim-3的表达,减少Th1细胞的分化,减轻结肠病灶区的炎症浸润,缓解克罗恩病病情进展。
Objective To investigate the therapeutic effect and mechanism of rapamycin on Crohn’s disease mouse model. Methods Thirty mice were randomly divided into three groups: M1 group (n = 10), M2 group (TNBS model group, n = 10), M3 group (TNBS + rapamycin group Group, n = 10). The rats in M1 group were treated with saline enema. The disease model of Crohn’s mice was established in M2 group and injected with saline by intraperitoneal injection. The disease model of Crohn’s mouse was established in M3 group and injected with Rapamycin intraperitoneally. The colon sections of mice were sacrificed at 7 days after modeling, HE staining was performed, and the colon and heart of the lesion were taken for blood collection. RNA reverse transcription and PCR were performed to detect the gene expression of Tim-1, Tim-3 and Foxp3 , Understand the correlation between the indicators. Results The CD model of mice was successfully constructed. Compared with M2 group, M3 group showed lower pathological score and mild disease, and the difference was statistically significant (P <0.05). Colonic tissue and peripheral blood: There was no significant difference in Tim-1mRNA between groups (P> 0.05). There was significant difference between Tim-3mRNA and Foxp3mRNA in all groups (P <0.05). The expression of Tim-3 mRNA was also negatively correlated with Foxp3 mRNA expression in colon tissues (r = -1.6275, P <0.05). Conclusion Rapamycin could reduce the expression of Tim-3, decrease the differentiation of Th1 cells, reduce the inflammatory infiltration in colorectal area and relieve the progression of Crohn’s disease by promoting the differentiation of regulatory T cells and increasing Foxp3 expression.