氯吡格雷在化學(xué)誘導(dǎo)小鼠結(jié)腸炎相關(guān)腫瘤發(fā)生中的作用（英文）
發(fā)布時間：2018-11-09 11:44
【摘要】：目的探究血小板聚集抑制劑氯吡格雷(Clog)對結(jié)腸炎相關(guān)結(jié)腸癌(CAC)形成過程的影響及其作用機制。方法雄性BALB/c小鼠分為5組,正常對照組,模型組,Clog 12.5,25.0和50.0 mg·kg~(-1)組。CAC模型組首先1次ip給予氧化偶氮甲烷(AOM)10 mg·kg~(-1),1周后,每天飲用〔2.5%葡聚糖硫酸鈉(DSS)1周+生理鹽水2周〕3個周期建立CAC模型。自給予2.5%DSS飲用水起,Clog 12.5,25.0和50.0 mg·kg~(-1)每天ig給藥1次至模型建立結(jié)束。記錄小鼠的體質(zhì)量,臨床癥狀,小鼠結(jié)腸腫瘤的數(shù)目和大小,HE染色評價腫瘤的異型性。在CAC小鼠早期炎癥階段,測量小鼠的結(jié)腸長度,HE染色和Ki67染色分別評價結(jié)腸組織病理變化和結(jié)腸組織上皮細胞的增殖水平。在腫瘤形成與發(fā)展階段,Ki67染色評價結(jié)腸組織上皮細胞增殖水平,實時熒光定量PCR法檢測腫瘤壞死因子α(TNF-α)m RNA的表達,PCR和免疫組化法檢測趨化因子(C-X-C結(jié)構(gòu)域)配體2(CXCL2)及其受體CXCR2的表達。結(jié)果與模型組相比,Clog 12.5 mg·kg~(-1)可緩解小鼠的臨床癥狀,減小結(jié)腸腫瘤平均直徑(P0.05),降低腫瘤異型性(P0.05)。在CAC早期炎癥階段,Clog 12.5 mg·kg~(-1)可緩解小鼠臨床癥狀(P0.05)和體質(zhì)量下降(P0.01),增加結(jié)腸長度(P0.01),減輕結(jié)腸組織炎癥損傷(P0.05),降低上皮細胞增殖水平(P0.05);在CAC腫瘤形成與發(fā)展階段,Clog 12.5 mg·kg~(-1)可降低結(jié)腸組織上皮細胞增殖水平(P0.05),減少結(jié)腸組織TNF-αm RNA水平、CXCL2和CXCR2 m RNA及蛋白表達水平(P0.05)。結(jié)論 Clog可緩解CAC早期炎癥階段的炎癥發(fā)展,抑制結(jié)腸腫瘤的形成。其抗腫瘤作用可能與減少CXCL2與CXCR2的表達有關(guān)。
[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 偽 (TNF- 偽) 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- 偽 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.
【作者單位】： 軍事醫(yī)學(xué)科學(xué)院毒物藥物研究所;山西醫(yī)科大學(xué)腫瘤醫(yī)院;中國人民解放軍總醫(yī)院;
【基金】：The project supported by National Science and Technology Major Project of China(2012-ZX09301003)~~
【分類號】：R965
本文編號：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 偽 (TNF- 偽) 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- 偽 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.
【作者單位】： 軍事醫(yī)學(xué)科學(xué)院毒物藥物研究所;山西醫(yī)科大學(xué)腫瘤醫(yī)院;中國人民解放軍總醫(yī)院;
【基金】：The project supported by National Science and Technology Major Project of China(2012-ZX09301003)~~
【分類號】：R965
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