二甲双胍、塞来昔布对化学诱导异常隐窝病灶预防机制的研究

目的 探讨二甲双胍、塞来昔布对氧化偶氮甲烷(AOM)诱导的异常隐窝病灶(ACF)的预防机制.方法 45只7周龄BALB/c雌性小鼠随机分为对照组、二甲双胍组、塞来昔布组3组,分别予腹腔注射AOM;同时对照组、二甲双胍组、塞来昔布组小鼠分别予生理盐水、二甲双胍、塞来昔布灌胃处理.每周监测小鼠体质量变化.6周后处死小鼠并分离结直肠组织,应用PCNA免疫组织化学染色及TUNEL染色的方法检测病变组织的增殖及凋亡的情况;使用ELISA检测小鼠空腹血糖、空腹胰岛素以评估小鼠胰岛素的抵抗状态. 结果 二甲双胍组和塞来昔布组的细胞增殖指数分别为(27.30±1.49)和(37.20±2.10),显著低于对照组(56.20±1.93) (P＜0.05),二甲双胍对细胞增殖的抑制作用强于塞来昔布(P＜0.05);二甲双胍组和塞来昔布组的细胞凋亡指数分别为(7.70±1.25)和(7.00±1.05),显著高于对照组(5.10±1.37)(P＜0.05);对照组、二甲双胍组、塞来昔布组的小鼠空腹血糖及胰岛素抵抗指数比较,差别无统计学意义(P＞0.05). 结论 二甲双胍、塞来昔布对大肠癌起到预防的作用,其机制可能与抑制细胞增殖及促进细胞凋亡有关;二甲双胍的作用明显优于塞来昔布.

Chemopreventive Mechanism of Metformin or Celecoxib on ChemicallyInduced Colorectal Aberrant Crypt Foci in Mice

Objective To investigate chemopreventive mechanism of metformin or celecoxib on chemically induced colorectal aberrant crypt foci in mice. Methods Forty five 6-week-old BALB/c female mice were randomly divided into 3 groups: control group, metformin group and celecoxib group. After one week adaptation, the mice were injected intraperitoneally with 10 mg/kg of AOM, once a week for two weeks. The mice in control group, metformin group and celecoxib group were treated with saline, metformin and celecoxib by gavage, respectively. The changes in body weight were monitored weekly in mice. After 6 weeks, mice were sacrificed and the colorectal tissues were separated. Proliferation of lesions tissue was detected by proliferating cell nuclear antigen(PCNA)labeling indices, and apoptosis was detected by transferase deoxynucleotidyl uridine end labeling(TUNEL)staining. Moreover, to assess the state of mice insulin resistance, the fasting plasma glucose and insulin in mice were detected. Results The proliferation index(PI)of metformin group and celecoxib group were respectively(27.30±1.49)and(37.20±2.10),which was lower than that of the control group(56.20±1.93), (P<0.05). Metformin had stronger inhibitory effect than celecoxib on cell proliferation(P<0.05). The apoptosis index(AI)in metformin group and celecoxib group were(7.70±1.25)and(7.00±1.05)respectively, which was higher than that in the control group(5.10±1.37), (P<0.05). No significant difference in fasting plasma glucose and insulin resistance index of mice was found between control group, metformin group and celecoxib group(P>0.05). Conclusion We confirm that metformin and celecoxib may play a preventive role for colorectal cancer. The mechanism may be related to the inhibition of cell proliferation and promoting of apoptosis. Moreover, the effect of metformin is better than celecoxib.