| 摘要: |
| 目的:建立结肠炎相关性结直肠癌(CAC)小鼠模型，研究鸦胆子油乳注射液(BJOEI)的抗癌作用及机制。方法:将60只SPF级C57BL/6雄性小鼠随机分为正常组、模型组、阿司匹林组和BJOEI低、中、高剂量组，每组10只。除空白组外，各组小鼠均采用氧化偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导CAC小鼠模型，从第3周开始，各组予以相应药物治疗，阿司匹林组25 mg/kg灌胃，BJOEI低、中、高剂量组分别以1.5 mL/kg、3.0 mL/kg、4.5 mL/kg剂量腹腔注射BJOEI，空白组和模型组腹腔注射等体积生理盐水，1次/d，连续给药10周后取材并记录结直肠肿瘤个数，计算脾脏指数；HE染色观察小鼠的结肠组织病理变化，并进行病理学评分；ELISA法检测小鼠血清IL-6水平；免疫组化检测结肠组织Ki67、肿瘤坏死因子(TNF)-α和血管内皮生长因子(VEGF)的表达；Western blot检测结肠组织磷酸化核因子-κB(p-NF-κB)/NF-κB蛋白相对表达量。结果:与模型组相比，BJOEI低、中、高剂量组肠道肿瘤个数和脾脏指数均减少，有统计学意义(P<0.05)，肠组织病理学评分和Ki67、TNF-α、VEGF、p-NF-κB/NF-κB表达水平均降低，有统计学意义(P<0.05)，BJOEI中、高剂量组血清IL-6水平降低，有统计学意义(P<0.05)。结论:BJOEI可能通过抑制NF-κB通路来减轻肠黏膜炎症反应发挥抗CAC作用。 |
| 关键词: 结肠炎相关性结直肠癌 鸦胆子油乳注射液 核因子-κB通路 |
| DOI：10.3969/j.issn.1007-6948.2024.05.022 |
| 投稿时间：2024-03-28 |
| 基金项目:山西省医学重点科研项目(2022XM10)；山西省卫生健康委科研课题(2023092)；中央引导地方科技发展资金项目(YDZJSX20231C020)；第二批国家中医临床研究基地建设项目(国中医药科技函〔2018〕131 号) |
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| Effect and mechanism of Brucea javanica oil emulsion injection on colitis-associated colorectal cancer mice |
| ZHAO Yan-mei-dai,WANG Jin-ming,NAN Peng |
| Shanxi University of Chinese Medicine, Shanxi Taiyuan (030024), China |
| Abstract: |
| Objective To establish a mouse model of colitis associated colorectal cancer (CAC) and study the anti-cancer effect and mechanism of brucea javanica oil emulsion injection (BJOEI) based on NF-κB pathway. Methods Sixty SPF grade C57BL/6 male mice were randomly divided into normal group, model group, aspirin group and BJOEI low, medium and high dose groups, with 10 mice in each group. Except the blank group, CAC mouse model was induced by azoomethane oxide (AOM) and dexosan sodium sulfate (DSS). Starting from the 3rd week, each group was given corresponding drug treatment, aspirin group was given 25 mg/kg intragastric administration. The low, medium and high dose groups of BJOEI were intraperitoneally injected at the doses of 1.5 mL/kg, 3.0 mL/kg and 4.5 mL/kg, respectively, and the blank group and model group were intraperitoneally injected with equal volume of normal saline once a day for 10 weeks. The number of colorectal tumors was recorded and the spleen index was calculated; HE staining was used to observe the pathological changes of colonic tissue in mice, and pathological score was performed. Serum IL-6 was detected by ELISA. The expressions of Ki67, TNF-α and VEGF were detected by immunohistochemistry. The relative expression of p-NF-κB/NF-κB protein in colon tissues was detected by Western blot. Results Compared with model group, the number of intestinal tumors and spleen index in low, medium and high dose BJOEI groups were decreased (P<0.05), and the intestinal histopathological scores and the expression levels of Ki67, TNF-α, VEGF, p-NF-κB/NF-κB were decreased (P<0.05). Serum IL-6 level was decreased in medium and high dose BJOEI groups (P<0.05). Conclusion BJOEI may play an anti-CAC role by inhibiting NF-κB pathway and alleviating intestinal mucosal inflammation. |
| Key words: Colitis-associated colorectal cancer brucea javanica oil emulsion injection nuclear factor kappa-B signaling pathway |
