General anesthetics inhibit erythropoietin induction under hypoxic conditions in the mouse brain.
General anesthetics inhibit erythropoietin induction under hypoxic conditions in the mouse brain.
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DOI：
10.1371/journal.pone.0029378
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hirota K
中科院分区：
文献类型：
--
作者：
Tanaka T;Kai S;Koyama T;Daijo H;Adachi T;Fukuda K;Hirota K
促红细胞生成素（EPO）最初被鉴定为在肾脏和胎肝中产生的造血生长因子，也在中枢神经系统（CNS）中内源性表达。中枢神经系统中的EPO主要在星形胶质细胞中产生，在缺氧条件下以缺氧诱导因子（HIF）依赖性方式被诱导，并且在神经保护和神经发生中起主导作用。我们研究了全身麻醉药对小鼠脑和原代培养星形胶质细胞中EPO表达的影响。将BALB/c小鼠暴露于含不同浓度（0.10-1.0%）异氟烷的10%氧气中。研究了脑中EPO mRNA的表达，并研究了七氟烷、氟烷、氧化亚氮、戊巴比妥、氯胺酮和丙泊酚的作用。此外，还通过免疫印迹法研究了HIF-2α蛋白的表达。异氟醚以浓度依赖性方式显著抑制缺氧诱导的脑内EPO mRNA表达。所有其他全身麻醉药均证实了类似的效果。异氟醚也显著抑制缺氧诱导的HIF-2α蛋白表达。在使用原代培养的星形胶质细胞的实验中，异氟烷、戊巴比妥和氯胺酮抑制缺氧诱导的HIF-2α蛋白和EPO mRNA的表达。总之，我们的研究结果表明，全身麻醉药抑制HIF-2的激活，并通过对星形胶质细胞的直接作用抑制缺氧诱导的EPO在小鼠脑中的上调。
Erythropoietin (EPO), originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS). EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF)-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes. BALB/c mice were exposed to 10% oxygen with isoflurane at various concentrations (0.10–1.0%). Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2α protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2α protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2α protein and EPO mRNA. Taken together, our results indicate that general anesthetics suppress activation of HIF-2 and inhibit hypoxia-induced EPO upregulation in the mouse brain through a direct effect on astrocytes.
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高压氧预处理诱导大鼠缺血耐受的机制涉及上调缺氧诱导因子-1α和促红细胞生成素。
影响因子：
3.3
作者：
Gu, Guo-Jun;Li, Yun-Ping;Sun, Xue-Jun
通讯作者：
Sun, Xue-Jun
影响因子：
3.5
作者：
Hemmings, HC
通讯作者：
Hemmings, HC
影响因子：
8.8
作者：
FINK, BR;HASCHKE, RH
通讯作者：
HASCHKE, RH
影响因子：
5.3
作者：
Chavez, Juan C.;Baranova, Oxana;Pichiule, Paola
通讯作者：
Pichiule, Paola
DOI：
10.1097/00004647-199906000-00007
发表时间：
1999-06-01
影响因子：
6.3
作者：
Bernaudin, M;Marti, HH;Petit, E
通讯作者：
Petit, E