研究动态
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在一种使用1,2-二甲基肼的实验性肠癌模型中,TNF-α和NFkβ的作用。

The role of TNF-α and NFkβ in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine.

发表日期:2023
作者: Márcio Alencar Barreira, Márcio Wilker Soares Campelo, Conceição da Silva Martins Rebouças, Ana Paula Bomfim Soares Campelo, Paulo Roberto Leitão de Vasconcelos
来源: Protein & Cell

摘要:

为了分析在1,2-DMH肠癌实验模型中,肿瘤坏死因子-α(TNF-α)和因子核聚合物κ B(NF-κB)作为结直肠癌(CRC)生物标志物的潜力。我们将24只雄性Wistar大鼠分成两组:假手术组和1,2-DMH组。首先,将1,2-DMH(20 mg/kg/week)连续给予15周。在第25周,进行直结肠和结肠切除术。进行组织病理学分析、免疫组化和TNF-α和NF-κB基因表达分析。使用GraphPad Prism进行统计分析。采用Kruskal-Wallis的检验方法分析异常小窝(ACF)的位置。对于带有参数数据的两组分析,使用t检验;对于非参数数据,使用Mann-Whitney的检验。P < 0.05被视为显著差异。1,2-DMH组的ACF和宏观病变的数量明显高于假手术组(p < 0.5),大部分ACF集中在结肠的远段。与假手术组相比,1,2-DMH组的TNF-α和NF-κB的蛋白质和基因表达明显增加(p < 0.5)。我们的研究结果提供了支持性证据,表明TNF-α和NF-κB通路在大鼠CRC发展中起着重要作用,并可能作为实验研究中CRC发病机制的早期生物标志物。
To analyze the potential of tumor necrosis factor-α (TNF-α) and factor nuclear kappa B (NF-κB) as colorectal cancer (CRC) biomarkers in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine (1,2-DMH).Twenty-four male Wistar rats were divided into two groups: sham and 1,2-DMH. First, 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. Histopathological analysis, immunohistochemistry, and gene expression of TNF-α and NF-κB were performed. Statistical analysis was performed using GraphPad Prism. The location of aberrant crypt foci (ACF) was analyzed by Kruskal-Wallis' test. For analyses with two groups with parametric data, the t-test was used; for non-parametric data, the Mann-Whitney's test was used. P < 0.05 was considered significant.The number of ACF and macroscopic lesions was significantly higher (p < 0.5) in the 1,2-DMH group compared to the sham group, and most ACF were concentrated in the distal segment of the colon. There was a statistically significant increase (p < 0.5) in protein and gene expression of TNF-α and NF-κB in the 1,2-DMH group compared to the sham group.Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.