三七皂苷和丹参酮ⅡA对炎症相关性结直肠癌小鼠的保护作用及对COX-2蛋白表达的抑制作用

Protective effect of notoginsenoside and tanshinone IIA on inflammation-related colorectal cancer mice and the inhibition effect on COX-2 expression

目的探讨三七总皂苷和丹参酮ⅡA对炎症相关性结直肠癌小鼠的预防作用及可能的作用机制。方法将88只C57BL/6雄性小鼠,按随机数字表法分为11组,每组8只;分别为氧化偶氮甲烷+葡聚糖硫酸钠(AOM+DSS)模型对照组,三七总皂苷低、中、高剂量组,丹参酮ⅡA低、中、高剂量组,三七总皂苷+丹参酮ⅡA低、中、高剂量组,空白组;前10组腹腔注射AOM诱导炎症相关结直肠癌,空白组腹腔注射等量0.9%Nacl溶液;前10组第5天开始连续自由饮用2.5%DSS水溶液,五天为一周期,每三周一个周期,共三个周期,空白对照组正常饮水。第3周开始药物组每天分别给予三七总皂苷低、中、高剂量,丹参酮ⅡA低、中、高剂量,三七总皂苷+丹参酮ⅡA低、中、高剂量灌胃,模型对照组与空白组给予生理盐水灌胃至实验结束。取材与指标检测:检测小鼠一般活动情况、体质量、存活率、腺癌发生率,免疫组织化学法检测COX-2水平表达变化。结果(1)存活率:三七总皂苷高剂量组,丹参酮ⅡA中、高剂量组,三七总皂苷+丹参酮ⅡA中、高剂量组炎症相关性结直肠癌小鼠的存活率显著提高,差异有统计学意义(P<0.05)。(2)肿瘤发生率:三七总皂苷+丹参酮ⅡA高剂量组、丹参酮ⅡA中剂量组、三七总皂苷低剂量组与模型组比较,肿瘤发生率显著降低,差异有统计学意义(P<0.05)。(3)与模型组比较,三七总皂苷+丹参酮ⅡA中、高剂量组小鼠瘤体组织COX-2表达水平显著降低,差异有统计学意义(P<0.05)。结论(1)三七总皂苷+丹参酮ⅡA高剂量、丹参酮ⅡA中剂量可以预防炎症相关性结直肠癌小鼠肿瘤的产生。(2)三七总皂苷+丹参酮ⅡA高剂量组可通过抑制COX-2途径预防炎症相关性结直肠癌发生。

Objective To explore the preventive effects and possible mechanisms of action of notoginsenoside(NGS)and tanshinone IIA(TSN)in inflammation-related colorectal cancer(IRCC)in mice.Methods Eighty-eight male C57BL/6 mice were randomly assigned to 11 groups(n=8 each group).Azomethane oxide+dextran sulfate(AOM+DSS)model control(model),NGS lowdose(l-NGS),NGS medium-dose(m-NGS),NGS high-dose(h-NGS),TSN low-dose(l-TSN),TSN medium-dose(m-TSN),TSN high-dose(h-TSN),(NGS+TSN)low-dose[l-(NGS+TSN)],(NGS+TSN)medium-dose[m-(NGS+TSN)],(NGS+TSN)high-dose[h-(NGS+TSN)],and blank groups were established.The first 10 groups were intraperitoneally injected with AOM to induce inflammatory colon cancer,whereas the blank group was intraperitoneally injected with 0.9%NaCl solution.The first 10 groups drank a 2.5%sodium DSS aqueous solution continuously from day 5 for three cycles(one cycle:five days,every three weeks),and the blank group was allowed free access to water.Drug groups were administered NGS(low,medium,or high dose),TSN(low,medium,or high dose),or NGS+TSN(low,medium,or high dose),and the model and blank groups were administered saline by lavage until the end of the experiment.The general activity,body weight,and survival rate of and incidence of adenocarcinoma in mice were detected and the expression of cyclooxygenase 2(COX-2)was detected by immunohistochemistry.Results(1)The survival rate of mice with IRCC in the h-NGS,m-TSN,h-TSN,m-(NGS+TSN),and h-(NGS+TSN)groups was significantly increased than that in other groups(P<0.05).(2)The incidence of tumors in the h-(NGS+TSN),m-TSN,and l-NGS groups was significantly lower than that in the model group(P<0.05).(3)The expression level of COX-2 in tumor tissues of mice in the m-(NGS+TSN)and h-(NGS+TSN)groups was significantly lower than that in the model group(P<0.05).Conclusion Tumor formation was inhibited by m-TSN and h-(NGS+TSN)treatments in mice with IRCC,and h-(NGS+TSN)treatment inhibited the COX-2 pathway.