二甲双胍、塞来昔布对小鼠结直肠息肉预防作用的比较

Comparison of chemopreventive effects of metformin or celecoxib on mice colorectal polyps

[目的]比较二甲双胍、塞来昔布对氧化偶氮甲烷(AOM)诱导的小鼠结直肠息肉的预防作用。[方法]66只6周龄BALB/c雌性小鼠适应1周后予腹腔注射AOM(10mg/kg),每周1次,连续6周;后随机分为对照组、二甲双胍组、塞来昔布组,对照组、二甲双胍组、塞来昔布组分别予0.9%氯化钠溶液(0.5ml/只)、二甲双胍250mg·kg^(-1)·d^(-1)、塞来昔布20mg·kg^(-1)·d^(-1)灌胃处理。30周后取出小鼠结直肠记录小鼠结直肠息肉发生的数目、大小,通过PCNA免疫组化染色及TUNEL染色检测息肉组织的增殖及凋亡的情况;检测小鼠胰岛素的抵抗状态以评估二甲双胍的间接作用。[结果]二甲双胍组小鼠息肉数量为(1.85±0.80)个,塞来昔布组小鼠息肉数量为(3.00±0.93)个,均较对照组的(4.13±1.06)个少(P<0.05);二甲双胍组息肉大小为(1.74±0.48)mm,塞来昔布组为(2.07±0.88)mm,也均较对照组的(2.54±0.82)mm小(P<0.05);与塞来昔布组相比,二甲双胍组可更加显著地减少AOM诱导的息肉的数量(P<0.05),但塞来昔布组与二甲双胍组间息肉大小比较差异无统计学意义(P>0.05);对照组增殖指数(PI)为67.50±5.04,高于二甲双胍组和塞来昔布组的37.90±3.48和46.10±6.19(P<0.05),且二甲双胍组显著低于塞来昔布组(P<0.05);对照组凋亡指数(AI)为3.60±1.17,低于二甲双胍组、塞来昔布组的6.20±1.40、5.80±1.03(P<0.05);另外,经二甲双胍、塞来昔布治疗后的小鼠胰岛素抵抗指数与对照组相比未出现明显的改变(P>0.05)。[结论]二甲双胍、塞来昔布均对AOM诱导的小鼠结直肠息肉具有预防作用,且二甲双胍的预防作用更显著,预防效果更稳定。

[Objective]To compare the chemoprophylactic effects of metformin and celecoxib on mice colorectal polyps model induced by azoxymethane（AOM）. [Methods] Sixty-six 6-week-old BALB/c female mice were randomly divided into 3 groups：control group,metformin group, celecoxib group. After one week adaptation,the mice were injected intraperitoneally with AOM（10 mg/kg）, once a week for six weeks. The control group was treated with saline alone by gavage, and the other two groups were treated with met- formin（250 rag. kg 1 . d^-1）or celecoxib（20 rag. kg 1 · d^-1）by gavage respectively. After 30 weeks,the number and size of colorectal polyps were recorded. Proliferation and apoptosis of polyps tissue were detec- ted by proliferating cell nuclear antigen（PCNA）labeling indices and transferase deoxynucleotidyl uridine end labeling（TUNEL）staining, respectively. In addition, the insulin resistance status was detected to assess indirect effects of metformin. [Results]The numbers of polyps in metformin group mice（1.85 ± 0.80）and the celecoxib group（3.00±0.93）were lower than that in the control group（4.13±1.06,P〈0.05）. And the average size of polyp in metformin group mice was 1.74±0. 48 mm and 2.07±0.88 mm in the celecox- ib group,which were both smaller than that in the control group（1.2.54±0.82]mm,P〈0.05）. The num- ber of polyps in metformin group was significantly less than celecoxib group（P〈0.05）, but there was no significant difference of the polyp size in the 2 groups. The proliferation index（PI）in control group was 67.50±5.04, which was higher than that in the metformin group （37.90± 3.48, P 〈 0.05） and＇ celecoxib gro up （46.10±6.19, P〈 0.05）. The apoptosis index （AI） in control group was 3.60 ±1.17, which was low- er than that in the metformin group （6.20 ± 1.40, P 〈 0.05） and eelecoxib group （5.80 ± 1.03, P〈 0.05）. Compared with the control group, no significant change of insulin resistance index was observed in met- formin and celecoxib group（P〉0.05）. [-Conclusion] Metformin and celecoxib may have chemopreventive effect on colorectal polyps induced by AOM in mice, and the ehemoprevention of metformin is more notable and stable than celecoxib.