Li Jun, Lv Yumin, Dong Xiuyun, Jin Zhu
Department of Digestive Disease, Peking University Third Hospital, Beijing 100083, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Oct;35(5):537-9.
To investigate the chemopreventive effects of pioglitazone (exogenous PPAR gamma ligand) on rat colon aberrant crypt foci, a rat carcinogenesis model induced by dimethylhydrazine (DMH), and to compare pioglitazone with sulindac (a NSAID).
Thirty-two, 8-week-old, female Sprague-Dawley rats were randomly divided into four groups (n = 8 each). Group 1 rats were injected with DMH alone (120 mg.kg-1, single subcutaneous injection). Group 2 rats were injected with saline alone. Group 3 rats were pre-treated with sulindac (320 mg.kg-1) for 7 days before DMH initiation. Group 4 rats were treated with pioglitazone (100 mg.kg-1). The animals were killed at the end of the experiment (week 5) and the colons were stained with methylene blue. The aberrant crypt foci (ACF) of the colonic mucosa were assessed.
In Group 1 rats (DMH only), the average numbers of ACF/colon and AC/colon were (182 +/- 93) and (263 +/- 198), respectively. In Group 2 (saline group) rats, no ACF were found. In Group 3 (sulindac group) rats, the average numbers of ACF/colon and AC/colon were (91 +/- 49) and (140 +/- 69), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). In Group 4 (pioglitazone group) rats, the average numbers of ACF/colon and AC/colon were (97 +/- 23) and (148 +/- 31), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). No difference was found in the values of Group 3 and Group 4.
These results suggest that pioglitazone have chemopreventive effects against rat colon carcinogenesis induced by DMH, whose effect is similar to that of sulindac.
研究吡格列酮（外源性过氧化物酶体增殖物激活受体γ配体）对二甲基肼（DMH）诱导的大鼠结肠癌发生模型——大鼠结肠异常隐窝灶的化学预防作用，并将吡格列酮与舒林酸（一种非甾体抗炎药）进行比较。
将32只8周龄雌性Sprague-Dawley大鼠随机分为四组（每组n = 8）。第1组大鼠单独注射DMH（120 mg·kg-1，单次皮下注射）。第2组大鼠单独注射生理盐水。第3组大鼠在开始注射DMH前用舒林酸（320 mg·kg-1）预处理7天。第4组大鼠用吡格列酮（100 mg·kg-1）治疗。在实验结束时（第5周）处死动物，结肠用亚甲蓝染色。评估结肠黏膜的异常隐窝灶（ACF）。
在第1组大鼠（仅注射DMH）中，平均每只结肠的ACF数量和AC数量分别为（182±93）和（263±198）。在第2组（生理盐水组）大鼠中，未发现ACF。在第3组（舒林酸组）大鼠中，平均每只结肠的ACF数量和AC数量分别为（91±49）和（140±69）。与第1组的值相比，两者均显著降低（P < 0.01和P < 0.05）。在第4组（吡格列酮组）大鼠中，平均每只结肠的ACF数量和AC数量分别为（97±23）和（148±31）。与第1组的值相比，两者均显著降低（P < 0.01和P < 0.05）。第3组和第4组的值之间未发现差异。
这些结果表明吡格列酮对DMH诱导的大鼠结肠癌发生具有化学预防作用，其作用与舒林酸相似。
