香连片对小鼠溃疡性结肠炎癌变过程中WIF-1和SFRP-1mRNA表达的影响

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目的探讨香连片对小鼠溃疡性结肠炎癌变过程中Wnt抑制因子1(WIF-1)和分泌型卷曲相关蛋白(SFRP-1)的影响。方法将60只BALB/C小鼠随机分为空白组(10只)、模型组(14只)、香连片低剂量组(12只)、香连片高剂量组(12只)和柳氮磺胺嘧啶组(12只)。除空白组外,其余各组采用DMH/DSS复合法诱导小鼠溃疡性结肠炎癌变模型,造模时间为18周。各组于造模前1周给予相应的干预措施,至造模的第10周结束;其中空白组和模型组予等量蒸馏水,各给药组给予相应的药物。用药时间为11周。观察小鼠体质量、粪便、耗食和精神状态等一般情况,结肠肿瘤的形成情况,HE染色镜下病变肠组织形态学改变,并以Real-time PCR检测WIF-1和SFRP-1mRNA的表达。结果在造模后期(第13~18周),模型组小鼠耗食减少,精神委靡,体质量明显减轻,与空白组比较,差异具有统计学意义(P<0.01);而香连片低剂量和高剂量组小鼠体质量下降与模型组比较无明显差异(P>0.05)。模型组结肠黏膜可见团块状肿块形成,HE染色可见模型组小鼠结肠黏膜腺体增生明显、细胞排列紊乱、核染色加深;香连片低剂量、高剂量组虽可见腺体增生,但细胞分化未见异型性。香连片各剂量组WIF-1 mRNA表达上调,与模型组比较,差异具有统计学意义(P<0.05);香连片各剂量组与模型组比较,SFRP-1mRNA表达差异无统计学意义(P>0.05)。结论香连片可以通过减轻小鼠溃疡性结肠炎延缓肠黏膜细胞的不典型增生,其机制与上调WIF-1基因的表达,从而抑制Wnt/β-catenin信号通路的异常激活有一定的关系。 Objective To investigate the effects of Xianglian Tablets on the expression of Wnt inhibitory factor 1 (WIF-1) and secreted frizzled-related protein (SFRP-1) during the development of ulcerative colitis in mice. Methods Sixty BALB/C mice were randomly divided into blank group (10 rats), model group (14 rats), Xianglian tablet low-dose group (12 rats), Xianglian tablet high-dose group (12 rats) and Liuzao group. Sulfadiazine group (12). Except for the blank group, the other groups were induced DMH/DSS complex method to induce the mouse model of ulcerative colitis, the modeling time was 18 weeks. Each group was given the corresponding intervention measures one week before the modeling, and it was finished in the tenth week of the modeling. The blank group and the model group were treated with equal amount of distilled water, and each administration group was given the corresponding drug. The medication time is 11 weeks. Observe the general conditions such as body weight, feces, food consumption, and mental status, the formation of colonic tumors, and the morphological changes of intestinal lesions under HE staining, and use Real-time PCR to detect the expression of WIF-1 and SFRP-1 mRNA. . Results In the late model establishment (13-18 weeks), the mice in the model group had reduced food consumption, mental euphemism, and reduced body weight. Compared with the blank group, the difference was statistically significant (P<0.01); There was no significant difference in the body weight of mice between the dose and high dose groups compared with the model group (P>0.05). The colonic mucosa of the model group showed clumpy masses. HE staining showed that the murine glandular hyperplasia of the mice in the model group was obvious, the arrangement of the cells was disordered and the nuclear staining was deepened; in the low-dose and high-dose groups of the conjunctiva, glandular hyperplasia was seen, but the cells There was no abnormality in differentiation. The expression of WIF-1 mRNA in each dose group of Xianglian Tablets was up-regulated, compared with the model group, the difference was statistically significant (P<0.05). There was no significant difference in the expression of SFRP-1 mRNA between Xianglian Tablets and the model group. P>0.05). Conclusion Chilianlian can relieve atypical hyperplasia of intestinal mucosal cells by reducing ulcerative colitis in mice. The mechanism is related to the up-regulation of WIF-1 gene expression, thus inhibiting the abnormal activation of Wnt/β-catenin signaling pathway.
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