去甲肾上腺素与红细胞生成之间的量效关系：临界阈值的证据。
Dose-response relationship between norepinephrine and erythropoiesis: evidence for a critical threshold.
机构信息
Department of Surgery, Division of Trauma University of Medicine and Dentistry New Jersey (UMDNJ)- New Jersey Medical School, Newark, New Jersey, USA.
出版信息
J Surg Res. 2010 Oct;163(2):e85-90. doi: 10.1016/j.jss.2010.03.051. Epub 2010 Apr 18.
BACKGROUND
Severe traumatic injury elicits a neuroendocrine response that activates the sympathetic nervous system. Our previous work suggests that norepinephrine (NE) influences the bone marrow (BM) erythropoietic response. However, the dose-response relationship between NE and erythropoiesis remains unclear.
MATERIALS AND METHODS
Two days following chemical sympathectomy with 6-hydroxydopamine (6-OHDA) or injection with saline vehicle (SHAM), male Sprague-Dawley rats were infused continuously with either saline (NS) or increasing doses of NE for 5 d via osmotic pumps. Erythropoiesis was assessed by growth of erythroid progenitor colonies (BFU-E and CFU-E for early and late progenitors, respectively).
RESULTS
Following chemical sympathectomy with 6-OHDA, both BFU-E and CFU-E growth is inhibited (42%∗ and 43%∗ versus 100% SHAM, ∗P < 0.05). SHAM rats with continuous infusion of exogenous NE show a clear dose-response inhibition of both BFU-E and CFU-E colony growth. In the 6-OHDA rats, continuous infusion of NE restored BFU-E and CFU-E growth at 10(-8) g/h and 10(-9) g/h, respectively.
CONCLUSIONS
Erythroid precursor colony growth is inhibited in sympathectomized rats. In addition, supraphysiologic doses of exogenous NE inhibit normal erythropoiesis in a dose-dependent fashion. Following chemical sympathectomy with 6-OHDA, exogenous NE restores erythropoiesis in a narrow window. Therefore, NE has a complex interaction within the BM and the elevation of NE following traumatic injury impacts BM erythropoietic function.
背景
严重创伤会引起神经内分泌反应，激活交感神经系统。我们之前的工作表明，去甲肾上腺素（NE）会影响骨髓（BM）的红细胞生成反应。然而，NE 与红细胞生成之间的剂量反应关系尚不清楚。
材料和方法
用 6-羟多巴胺（6-OHDA）进行化学性交感神经切除术或注射生理盐水载体（SHAM）两天后，雄性 Sprague-Dawley 大鼠通过渗透泵连续 5 天输注生理盐水（NS）或递增剂量的 NE。通过红系祖细胞集落（BFU-E 和 CFU-E 分别代表早期和晚期祖细胞）的生长来评估红细胞生成。
结果
用 6-OHDA 进行化学性交感神经切除术后，BFU-E 和 CFU-E 的生长均受到抑制（分别为 42%∗和 43%∗与 100%SHAM 相比，∗P < 0.05）。SHAM 大鼠连续输注外源性 NE 可明显抑制 BFU-E 和 CFU-E 集落生长。在 6-OHDA 大鼠中，连续输注 NE 可分别在 10(-8)g/h 和 10(-9)g/h 恢复 BFU-E 和 CFU-E 的生长。
结论
交感神经切除术后红系前体细胞集落生长受到抑制。此外，外源性 NE 的超生理剂量以剂量依赖性方式抑制正常的红细胞生成。用 6-OHDA 进行化学性交感神经切除术后，外源性 NE 可在一个狭窄的窗口内恢复红细胞生成。因此，NE 在 BM 内具有复杂的相互作用，创伤后 NE 的升高会影响 BM 的红细胞生成功能。
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