氯吡格雷在化学诱导小鼠结肠炎相关肿瘤发生中的作用（英文）
发布时间：2018-11-09 11:44
【摘要】：目的探究血小板聚集抑制剂氯吡格雷(Clog)对结肠炎相关结肠癌(CAC)形成过程的影响及其作用机制。方法雄性BALB/c小鼠分为5组,正常对照组,模型组,Clog 12.5,25.0和50.0 mg·kg~(-1)组。CAC模型组首先1次ip给予氧化偶氮甲烷(AOM)10 mg·kg~(-1),1周后,每天饮用〔2.5%葡聚糖硫酸钠(DSS)1周+生理盐水2周〕3个周期建立CAC模型。自给予2.5%DSS饮用水起,Clog 12.5,25.0和50.0 mg·kg~(-1)每天ig给药1次至模型建立结束。记录小鼠的体质量,临床症状,小鼠结肠肿瘤的数目和大小,HE染色评价肿瘤的异型性。在CAC小鼠早期炎症阶段,测量小鼠的结肠长度,HE染色和Ki67染色分别评价结肠组织病理变化和结肠组织上皮细胞的增殖水平。在肿瘤形成与发展阶段,Ki67染色评价结肠组织上皮细胞增殖水平,实时荧光定量PCR法检测肿瘤坏死因子α(TNF-α)m RNA的表达,PCR和免疫组化法检测趋化因子(C-X-C结构域)配体2(CXCL2)及其受体CXCR2的表达。结果与模型组相比,Clog 12.5 mg·kg~(-1)可缓解小鼠的临床症状,减小结肠肿瘤平均直径(P0.05),降低肿瘤异型性(P0.05)。在CAC早期炎症阶段,Clog 12.5 mg·kg~(-1)可缓解小鼠临床症状(P0.05)和体质量下降(P0.01),增加结肠长度(P0.01),减轻结肠组织炎症损伤(P0.05),降低上皮细胞增殖水平(P0.05);在CAC肿瘤形成与发展阶段,Clog 12.5 mg·kg~(-1)可降低结肠组织上皮细胞增殖水平(P0.05),减少结肠组织TNF-αm RNA水平、CXCL2和CXCR2 m RNA及蛋白表达水平(P0.05)。结论 Clog可缓解CAC早期炎症阶段的炎症发展,抑制结肠肿瘤的形成。其抗肿瘤作用可能与减少CXCL2与CXCR2的表达有关。
[Abstract]:Objective to investigate the effect and mechanism of clopidogrel (Clog), a platelet aggregation inhibitor, on the formation of (CAC) in colitis associated colon cancer. Methods male BALB/c mice were divided into 5 groups: normal control group, model group, Clog 12.5N 25.0 and 50.0 mg kg~ (-1) groups. The CAC model group was treated with (AOM) 10 mg kg~ (-1) for 1 week. The CAC model was established by drinking 2.5% sodium dextran sulfate (DSS) 1 week for 2 weeks) for 3 cycles. Clog 12.5 mg kg~ 25.0 and 50.0 mg kg~ (-1) ig were administered once a day to the end of model establishment since the administration of 2.5%DSS drinking water. The body weight, clinical symptoms, the number and size of colonic neoplasms in mice were recorded, and the heterogeneity of tumor was evaluated by HE staining. In the early stage of inflammation in CAC mice, the colonic length, the pathological changes of colonic tissue and the proliferation of colonic epithelial cells were evaluated by HE staining and Ki67 staining, respectively. At the stage of tumor formation and development, Ki67 staining was used to evaluate the proliferation of colonic epithelial cells, and real-time quantitative PCR was used to detect the expression of tumor necrosis factor 伪 (TNF- 伪) m RNA). PCR and immunohistochemistry were used to detect the expression of chemokine (C-X-C domain) ligand 2 (CXCL2) and its receptor CXCR2. Results compared with the model group, Clog 12.5 mg kg~ (-1) alleviated the clinical symptoms, decreased the mean diameter of colon tumor (P0.05) and decreased tumor heterogeneity (P0.05). In the early inflammatory stage of CAC, Clog 12.5 mg kg~ (-1) alleviated the clinical symptoms (P0.05) and decreased body mass (P0.01), increased the length of colon (P0.01), and alleviated the inflammatory injury of colon (P0.05). The proliferation level of epithelial cells was decreased (P0.05). At the stage of tumor formation and development of CAC, Clog 12.5 mg kg~ (-1) decreased the proliferation of colonic epithelial cells (P0.05), decreased the level of TNF- 伪 m RNA, CXCL2, CXCR2 m RNA and protein expression (P0.05). Conclusion Clog can relieve the inflammation and inhibit the formation of colon tumor in the early inflammatory stage of CAC. Its antitumor effect may be related to the reduction of the expression of CXCL2 and CXCR2.
【作者单位】： 军事医学科学院毒物药物研究所;山西医科大学肿瘤医院;中国人民解放军总医院;
【基金】：The project supported by National Science and Technology Major Project of China(2012-ZX09301003)~~
【分类号】：R965
本文编号：2320317
[Abstract]:Objective to investigate the effect and mechanism of clopidogrel (Clog), a platelet aggregation inhibitor, on the formation of (CAC) in colitis associated colon cancer. Methods male BALB/c mice were divided into 5 groups: normal control group, model group, Clog 12.5N 25.0 and 50.0 mg kg~ (-1) groups. The CAC model group was treated with (AOM) 10 mg kg~ (-1) for 1 week. The CAC model was established by drinking 2.5% sodium dextran sulfate (DSS) 1 week for 2 weeks) for 3 cycles. Clog 12.5 mg kg~ 25.0 and 50.0 mg kg~ (-1) ig were administered once a day to the end of model establishment since the administration of 2.5%DSS drinking water. The body weight, clinical symptoms, the number and size of colonic neoplasms in mice were recorded, and the heterogeneity of tumor was evaluated by HE staining. In the early stage of inflammation in CAC mice, the colonic length, the pathological changes of colonic tissue and the proliferation of colonic epithelial cells were evaluated by HE staining and Ki67 staining, respectively. At the stage of tumor formation and development, Ki67 staining was used to evaluate the proliferation of colonic epithelial cells, and real-time quantitative PCR was used to detect the expression of tumor necrosis factor 伪 (TNF- 伪) m RNA). PCR and immunohistochemistry were used to detect the expression of chemokine (C-X-C domain) ligand 2 (CXCL2) and its receptor CXCR2. Results compared with the model group, Clog 12.5 mg kg~ (-1) alleviated the clinical symptoms, decreased the mean diameter of colon tumor (P0.05) and decreased tumor heterogeneity (P0.05). In the early inflammatory stage of CAC, Clog 12.5 mg kg~ (-1) alleviated the clinical symptoms (P0.05) and decreased body mass (P0.01), increased the length of colon (P0.01), and alleviated the inflammatory injury of colon (P0.05). The proliferation level of epithelial cells was decreased (P0.05). At the stage of tumor formation and development of CAC, Clog 12.5 mg kg~ (-1) decreased the proliferation of colonic epithelial cells (P0.05), decreased the level of TNF- 伪 m RNA, CXCL2, CXCR2 m RNA and protein expression (P0.05). Conclusion Clog can relieve the inflammation and inhibit the formation of colon tumor in the early inflammatory stage of CAC. Its antitumor effect may be related to the reduction of the expression of CXCL2 and CXCR2.
【作者单位】： 军事医学科学院毒物药物研究所;山西医科大学肿瘤医院;中国人民解放军总医院;
【基金】：The project supported by National Science and Technology Major Project of China(2012-ZX09301003)~~
【分类号】：R965
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