吡格列酮对二甲基肼诱导的大鼠畸变隐窝灶的抑制作用

目的 :明确吡格列酮 (噻唑烷二酮类药物 ,外源性过氧化物酶体增生物激活受体γ配体 ,PPARγ)对二甲基肼 (DMH)诱导的大鼠畸变隐窝灶 (ACF)的影响 ,并与非甾体类抗炎药舒林酸进行比较。方法 :8周龄雌性SD大鼠 ,共 32只 ,随机分为 4组 ,每组 8只。第 1组为模型对照组 (DMH组 ) ,大鼠腹腔注射DMH(12 0mg·kg-1) ;第 2组为阴性对照组 ,大鼠腹腔注射生理盐水 (每只 1ml) ,两组均给予普通饲料喂养。第 3组为舒林酸组 ,用含有舒林酸 (32 0mg·kg-1)的饲料喂养 ,1周后腹腔注射DMH(12 0mg·kg-1)。第 4组为吡格列酮组 ,用含有吡格列酮 (10 0mg·kg-1)的饲料喂养 ,1周后腹腔注射DMH(12 0mg·kg-1)。含药饲料均喂养到实验结束。所有大鼠在注射DMH 5周后处死 ,计数每只大鼠大肠黏膜中ACF个数以及每个ACF中隐窝 (AC)个数。结果 :DMH组中 ,平均每只大鼠大肠中ACF为 (182± 93)个 ,AC为 (2 6 3± 198)个 ;生理盐水组中未见明显ACF ;舒林酸组ACF和AC分别为 (91± 4 9)个和 (14 0± 6 9)个 ,与DMH组相比 ,分别减少 5 0 .0 % (P <0 .0 1)和 4 6 .9% (P <0 .0 5 )。吡格列酮组ACF和AC分别为 (97± 2 3)个和 (14 8± 31)个 ,与DMH组相比 ,分别减少 4 7.0 % (P <0 .0 1)和 4 3.9% (P <0 .0 5 )。吡格列酮组与舒林酸组ACF及AC

Pioglitazone, a peroxisome proliferators-activated receptor gamma ligand, inhibits dimethylhydrazine (DMH) induced aberrant crypt foci in rats

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: These results suggest that pioglitazone have chemopreventive effects against rat colon carcinogenesis induced by DMH, whose effect is similar to that of sulindac.