Sustained increase in the proliferation of rat colonic mucosa during chronic treatment with aspirin.
Sustained increase in the proliferation of rat colonic mucosa during chronic treatment with aspirin.
复制标题
阿司匹林长期治疗期间大鼠结肠粘膜增殖持续增加。
DOI：
10.1016/0016-5085(88)90225-9
复制
发表时间：
1988
期刊：
影响因子：
29.4
通讯作者：
DeRubertis,FR
中科院分区：
文献类型：
--
作者：
Craven,PA;Thornburg,K;DeRubertis,FR
观察吲哚美辛和阿司匹林对结肠上皮细胞增殖活性、结肠前列腺素合成和结肠粘膜环腺苷酸含量的影响。给药吲哚美辛（3 mg/kg/天，s.c.）2wk抑制离体结肠前列腺素E2的产生50%，并增加体内[3H]胸苷掺入粘膜DNA，但诱导结肠炎症。较高剂量的吲哚美辛是有毒的，并与高死亡率有关。相比之下，给予阿司匹林（50 mg/kg·d，s.c.）给药2 - 20周可抑制结肠前列腺素E2的产生达97%，与结肠炎症或全身毒性无关。结肠前列腺素E2产生的抑制与[3H]胸苷掺入结肠粘膜脱氧核糖核酸（2 - 20周）的持续刺激和20周时检查的[3H]胸苷标记指数增加有关。阿司匹林治疗组大鼠结肠粘膜基础环磷酸腺苷含量明显降低。此外，加入二甲基前列腺素E2或8-Br-环腺苷3 ′，5 ′-单磷酸抑制[3H]胸苷掺入阿司匹林处理大鼠培养的结肠段粘膜脱氧核糖核酸的水平升高。结果表明，阿司匹林持续抑制结肠前列腺素合成与结肠上皮细胞增殖活性的持续增加有关。它们支持局部结肠前列腺素合成作为上皮生长的负调节剂的作用，可能通过结肠粘膜环腺苷3 ′，5 ′-单磷酸的增加介导。
The effects of indomethacin and aspirin on colonic epithelial proliferative activity, colonic prostaglandin synthesis, and colonic mucosal cyclic adenosine 3′,5′-monophosphate content were examined. Administration of indomethacin (3 mg/kg day, s.c.) for 2 wk suppressed ex vivo colonic prostaglandin E2production by 50% and increased [3H]thymidine incorporation into mucosal DNA in vivo, but induced colonic inflammation. Higher doses of indomethacin were toxic and associated with high mortality. By contrast, administration of aspirin (50 mg/kg · day, s.c.) for 2–20 wk suppressed colonic prostaglandin E2production by 97% and was unassociated with colonic inflammation or systemic toxicity. Suppression of colonic prostaglandin E2production was associated with a sustained stimulation of [3H]thymidine incorporation into colonic mucosal deoxyribonucleic acid (2–20 wk) and an increase in the [3H]thymidine labeling index when examined at 20 wk. Basal cyclic adenosine 3′,5′monophosphate content of colonic mucosa was markedly reduced in aspirin-treated rats. Moreover, addition of dimethyl prostaglandin E2or 8-Br-cyclic adenosine 3′,5′-monophosphate suppressed the elevated levels of [3H]thymidine incorporation into mucosal deoxyribonucleic acid in incubated colonic segments from aspirin-treated rats. The results demonstrate that sustained suppression of colonic prostaglandin synthesis by aspirin is associated with a persistent increase in colonic epithelial proliferative activity. They support a role for local colonic prostaglandin synthesis as a negative modulator of epithelial growth, possibly mediated through increases in colonic mucosal cyclic adenosine 3′,5′-monophosphate.