Lam T T, Rubin D, Drab E A
Radiat Res. 1985 Aug;103(2):240-50.
Experiments were conducted to determine (1) whether glucocorticoids directly protected endothelial cells (EC) from radiation and (2) if angiotensin converting enzyme (ACE) activity, known to be increased by glucocorticoid, played a role in the EC response to radiation. Confluent monolayers of EC cultured from bovine aorta EC were treated with dexamethasone (10(-6) M); after irradiation (5.0 Gy, 60Co gamma), ACE and lactate dehydrogenase (LDH) activities, DNA and protein contents, and nuclei number were measured. Twenty-four hours after 5 Gy, there was increased cell loss (-40%, P less than 0.001), greater LDH release (greater than 100%, P less than 0.001), more LDH activity per cell (+40%, P less than 0.001), and unchanged ACE activity compared to sham-irradiated control EC. However, 48 hr after 5 Gy, ACE activity per cell was decreased (-24%, P less than 0.005). A 48-hr exposure to dexamethasone alone was accompanied by a slight cell loss (-10%, P less than 0.001) and increased cellular ACE activity (+40-140%, P less than 0.001), but a 24-hr dexamethasone exposure was not cytotoxic and did not change ACE activity. Dexamethasone exposure for 48 hr before and after irradiation did not attenuate cell loss or LDH release. However, combined dexamethasone treatment and radiation increased cellular ACE activity at a time when neither agent alone had an effect (24-hr dexamethasone exposure before 5 Gy and assayed 24 hr after 5 Gy). This interaction between radiation and dexamethasone treatment suggests that the glucocorticoid modifies the cell's response to injury. Although this interaction does not ameliorate radiation cytotoxicity, maintenance of ACE levels in injured vessels by hormones may have physiological significance in the hemodynamics of irradiated tissues.
(1) 糖皮质激素是否直接保护内皮细胞 (EC) 免受辐射；(2) 已知可被糖皮质激素升高的血管紧张素转换酶 (ACE) 活性是否在 EC 对辐射的反应中起作用。用牛主动脉 EC 培养的汇合单层 EC 用地塞米松 (10(-6) M) 处理；照射 (5.0 Gy, 60Co γ) 后，测量 ACE 和乳酸脱氢酶 (LDH) 活性、DNA 和蛋白质含量以及细胞核数量。5 Gy 照射 24 小时后，与假照射对照 EC 相比，细胞损失增加 (-40%, P < 0.001)，LDH 释放增加 (大于 100%, P < 0.001)，每个细胞的 LDH 活性增加 (+40%, P < 0.001)，而 ACE 活性未改变。然而，5 Gy 照射 48 小时后，每个细胞的 ACE 活性降低 (-24%, P < 0.005)。单独暴露于地塞米松 48 小时伴随着轻微的细胞损失 (-10%, P < 0.001) 和细胞 ACE 活性增加 (+40 - 140%, P < 0.001)，但 24 小时地塞米松暴露无细胞毒性且未改变 ACE 活性。照射前后地塞米松暴露 48 小时并未减轻细胞损失或 LDH 释放。然而，地塞米松治疗与辐射联合在单独使用任何一种药物均无作用时增加了细胞 ACE 活性 (5 Gy 前暴露 24 小时地塞米松并在 5 Gy 后 24 小时测定)。辐射与地塞米松治疗之间的这种相互作用表明糖皮质激素改变了细胞对损伤的反应。虽然这种相互作用并未改善辐射细胞毒性，但激素维持受损血管中 ACE 水平可能在受照射组织的血流动力学中具有生理意义。
