摘要
目的初步探讨复方血竭制剂对实验性溃疡性结肠炎相关结直肠癌(UCRCC)的疗效及可能机制。方法 60只5周龄BALB/c小鼠按照随机原则分为正常组、模型组、低剂量复方血竭治疗组和高剂量复方血竭治疗组,实验中进行疾病活动指数(DAI)评分,造模11周后处死小鼠,取出回盲部至肛门全部结直肠,行大体及组织学观察,检测各组结直肠组织β-catenin活化水平以及c-myc、PCNA基因转录、总蛋白表达量。结果模型组肉眼可见黏膜明显充血、水肿,多处息肉状隆起形成;镜下可见大量炎性细胞浸润及不同程度上皮内瘤变,散在癌变表现。两治疗组肉眼可见黏膜充血、水肿,偶见息肉状隆起;镜下可见炎性细胞浸润,少量低级别上皮内瘤变,未见癌变。与正常组相比,模型组及两治疗组小鼠DAI评分以及结肠上皮细胞β-catenin蛋白入核量、c-myc和PCNA基因的mRNA转录及蛋白表达量均显著升高(P<0.05),两治疗组之间差异无统计学意义,但较模型组均显著降低(P<0.05)。各组小鼠结肠上皮细胞β-catenin基因在mRNA转录水平无明显差异。结论复方血竭制剂能够显著延缓实验性UCRCC的发生,其机制可能与促进结肠组织炎症缓解以及抑制Wnt/β-catenin通路的激活有关。
Objective To investigate the therapeutic effects and mechanism of compound dracorhodin on experi- mental ulcerative colitis related colorectal cancer（UCRCC）. Methods Sixty male BALB/c mice were randomly assigned to four groups （n= 15 ） ：blank control group, model group, low dose of compound dracorhodin group and high dose of compound dracorhodin group. Disease activity index（DAI） was evaluated daily during the experiment. Mice were sacrificed after 11 weeks, from which the colons and rectums were removed. The colon histomorphology was observed by naked eyes and microscope. The expressions of β-catenin, c-myc and PCNA were detected by Western blot and real time quantitative PCR. Results In the model group, obvious congestion, edema and polyps were found by naked eyes; lots of inflammatory cells, different degrees of intraepithelial neoplasia and even carci- noma were observed under microscope. In the compound dracorhodin groups, mucosal congestion, edema were ob- served, and the number of polyps was reduced ; inflammatory cells and a small amount of low-grade intraepithelial neoplasia were found under the microscope, no cancer was observed. Compared with the blank group, the DAI scores, nucleus localization of f3-catenin protein, the mRNA transcription and protein expression level of c-myc and PCNA were significantly higher（P 〈 0. 05 ） in the model group and the treatment groups（P 〈 0. 05 ）. There was no significant difference between the compound dracorhodin groups, but significantly decreased, compared with the model group （ P 〈 0. 05 ）. The transcription level of β-catenin showed no significant difference among 4 groups. Conclusion Compound dracorhodin reduced malignant transformation of experimental ulcerative colitis at least partially through relieving the inflammatory reaction and inhibiting the Wnt/β-catenin pathway.
出处
《安徽医科大学学报》
CAS
北大核心
2017年第1期13-17,共5页
Acta Universitatis Medicinalis Anhui
基金
北京市自然科学基金(编号:7132175)
