Hurst P R, Peplow P V
Br J Pharmacol. 1986 Sep;89(1):199-205. doi: 10.1111/j.1476-5381.1986.tb11136.x.
When indomethacin was incorporated into a slow-release preparation (initial content 1.6 mg drug) and placed in one horn of the rat uterus, a significant decrease in protein synthesis occurred for this horn in comparison with control animals (as determined by the incorporation of radioactive leucine) at three different times after insertion. Decreases of 20, 21% at the two times of dioestrus and 28% at the time of oestrus selected were determined. No significant reduction in protein synthesis was found for the contralateral horn, although there was a tendency for it to be lowered at the earliest time of examination when two complete oestrous cycles had passed following insertion. Measurement of the uptake of radioactive leucine by the uterine horns showed no change in response to indomethacin delivery compared to the control animals with silastic implants, and suggested that the transport system for this amino acid in cells of the uterine horns was not affected by the drug. It was apparent that in instances when the protein synthesis of the uterine horn was impaired by indomethacin that a decrease in RNA/DNA ratio existed. At the latest time examined, no alteration in DNA content occurred in the indomethacin-influenced horn but there was a significant reduction in RNA content. For a small proportion of the animals with indomethacin-releasing preparations there was a tendency to show a lengthening of the oestrous cycle over the first three cycles following insertion. Whether this was due to a direct effect of indomethacin on the ovaries or an effect caused by decreased concentrations of prostaglandins in the uterus was unknown. 5 These results provide further evidence that non-steroidal anti-inflammatory drugs can interfere with the synthesis of macromolecular substances, and that such changes need to be taken into account when considering the overall effect of these drugs on tissues and organs.
当吲哚美辛被制成缓释制剂（初始药物含量为1.6毫克）并置于大鼠子宫的一个角时，与对照动物相比（通过放射性亮氨酸掺入法测定），在插入后的三个不同时间点，该角的蛋白质合成显著减少。在选定的两个动情间期分别减少了20%、21%，在动情期减少了28%。对侧子宫角的蛋白质合成没有显著降低，尽管在插入后经过两个完整动情周期的最早检查时间点有降低的趋势。与植入硅橡胶的对照动物相比，子宫角对吲哚美辛释放的放射性亮氨酸摄取量测量显示没有变化，这表明子宫角细胞中这种氨基酸的转运系统不受该药物影响。显然，在吲哚美辛损害子宫角蛋白质合成的情况下，RNA/DNA比值会降低。在最晚检查时间点，受吲哚美辛影响的子宫角DNA含量没有改变，但RNA含量显著降低。对于一小部分使用释放吲哚美辛制剂的动物，在插入后的前三个周期有动情周期延长的趋势。这是由于吲哚美辛对卵巢的直接作用还是子宫中前列腺素浓度降低所致尚不清楚。5这些结果进一步证明非甾体抗炎药可干扰大分子物质的合成，并且在考虑这些药物对组织和器官的整体作用时需要考虑到这种变化。
