Uribe A, Garberg L
Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
Prostaglandins. 1990 Jul;40(1):1-11. doi: 10.1016/0090-6980(90)90052-w.
The aim of the study was to examine the mitotic activity in the antral and duodenal epithelium of Sprague-Dawley rats given trophic doses of E2 prostaglandins during a prolonged period of time. Natural prostaglandin E2 (dose range: 0.2-5.0 mg.k-1) and 15 (R) 15 methyl prostaglandin E2 (dose range: 0.03-2.0 mg.kg-1) were administered for 11 days, and mitoses were arrested with vincristine for 4 h before estimation of the cumulative mitotic index. A dose-related hyperplasia of the antral glands was observed after treatment with prostaglandin E2 and the synthetic analogue (p less than 0.05). The proliferative zone was enlarged in rats treated with high doses of the analogue but natural prostaglandin E2 did not affect the limits of the proliferative zone. A dose-related reduction of the mitotic index was observed in animals treated with prostaglandin E2 despite the presence of hyperplastic changes. All doses of the analogue induced antral hyperplasia without affecting the mitotic index except in rats given the highest dose who had a significantly lower mitotic index than controls (p less than 0.05). Hyperplasia of both crypts and villi was observed in the duodenum of rats given high doses of E2 prostaglandins (p less than 0.05) whereas the mitotic index and the growth fraction were not affected by treatments. It is concluded that hyperplasia by prostaglandins is developed in absence of changes of the mitotic activity. The observed reduction of the mitotic index is interpreted as a secondary phenomenon, possibly mediated by a regulatory mechanism of cell proliferation which is triggered to reduce further epithelial growth. It is suggested that prostaglandin E2 might influence such regulatory mechanisms.
本研究的目的是检测长期给予营养剂量的E2前列腺素的Sprague-Dawley大鼠胃窦和十二指肠上皮的有丝分裂活性。给予天然前列腺素E2（剂量范围：0.2 - 5.0 mg·kg-1）和15（R）15-甲基前列腺素E2（剂量范围：0.03 - 2.0 mg·kg-1）11天，在估计累积有丝分裂指数前用长春新碱使有丝分裂停滞4小时。用前列腺素E2和合成类似物处理后观察到胃窦腺呈剂量相关的增生（p < 0.05）。高剂量类似物处理的大鼠增殖区扩大，但天然前列腺素E2不影响增殖区界限。尽管存在增生性改变，但用前列腺素E2处理的动物有丝分裂指数呈剂量相关降低。除给予最高剂量的大鼠有丝分裂指数显著低于对照组（p < 0.05）外，所有剂量的类似物均诱导胃窦增生但不影响有丝分裂指数。给予高剂量E2前列腺素的大鼠十二指肠隐窝和绒毛均增生（p < 0.05），而处理不影响有丝分裂指数和生长分数。得出结论：前列腺素引起的增生在有丝分裂活性无变化的情况下发生。观察到的有丝分裂指数降低被解释为一种继发现象，可能由细胞增殖的调节机制介导，该机制被触发以减少上皮的进一步生长。提示前列腺素E2可能影响这种调节机制。
