Sustained stimulation of rat adrenal chromaffin cell proliferation by reserpine.
Sustained stimulation of rat adrenal chromaffin cell proliferation by reserpine.
复制标题
利血平持续刺激大鼠肾上腺嗜铬细胞增殖。
DOI：
10.1006/taap.1995.1231
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
McClain,RM
中科院分区：
文献类型：
--
作者：
Tischler,AS;Ziar,J;Downing,JC;McClain,RM
长期服用利血平与大鼠嗜铬细胞瘤的发生有关。大鼠短期服用利血平可刺激嗜铬细胞增殖，导致假设利血平通过提供可能发生遗传损伤的增殖背景间接导致嗜铬细胞瘤。然而，目前尚不清楚利血平的增殖效应是否持续足够长的时间，使该模型能够站得住脚。本文研究了利血平对肾上腺素(E)和去甲肾上腺素(NE)型嗜铬细胞掺入溴脱氧尿苷(BrdU)的影响。利血平在饮食中以10或50ppm给药，显示出对大鼠肾上腺髓质的持续促有丝分裂刺激。在各时间点掺入BrdU的细胞均为典型的E和NE型嗜铬细胞，且BrdU标记的E细胞和BrdU标记的NE细胞的比例不受利血平的影响。另一个观察结果是，所有E细胞与所有NE细胞的比率在1周后下降，利血平可以加速这种下降。这一发现表明，对嗜铬细胞的神经刺激可能在成年早期肾上腺髓质与年龄相关的功能变化中发挥作用。目前的观察结果支持利血平通过促进嗜铬细胞增殖间接诱导嗜铬细胞瘤的假说。它们还降低了大鼠嗜铬细胞瘤发生的可能性，这种可能性是由特定细胞类型的增殖优先刺激引起的。
Chronic administration of reserpine is associated with the development of pheochromocytomas in rats. Short-term administration of reserpine to rats has been shown to stimulate chromaffin cell proliferation, leading to the hypothesis that reserpine causes pheochromocytomas indirectly by providing a proliferative backdrop on which genetic damage may occur. However, it is not known whether the proliferative effects of reserpine persist long enough for this model to be tenable. In the present investigation, the effects of reserpine on bromodeoxyuridine (BrdU) incorporation into epinephrine (E)- and norepinephrine (NE)-type chromaffin cells were studied after 1, 4, and 12 weeks of reserpine administration. Reserpine administered in the diet at 10 or 50 ppm was shown to result in a persistent mitogenic stimulation of the rat adrenal medulla. Cells that incorporated BrdU at all time points appeared to be typical E- and NE-type chromaffin cells, and the ratio of BrdU-labeled E cells to BrdU-labeled NE cells was not altered by reserpine. An additional observation was that the ratio of all E cells to all NE cells declined after Week 1 and that the decline could be accelerated by administration of reserpine. This finding suggests that neural stimulation of chromaffin cells might play a role in age-related functional changes of the adrenal medulla during early adult life. The present observations support the hypothesis that reserpine induces pheochromocytomas indirectly by increasing chromaffin cell proliferation. They also decrease the likelihood that rat pheochromocytomas arise from preferential stimulation of proliferation of a particular cell type.