Sevoflurane Inhibits Glutamate-Aspartate Transporter and Glial Fibrillary Acidic Protein Expression in Hippocampal Astrocytes of Neonatal Rats Through the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) Pathway
Sevoflurane Inhibits Glutamate-Aspartate Transporter and Glial Fibrillary Acidic Protein Expression in Hippocampal Astrocytes of Neonatal Rats Through the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) Pathway
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七氟醚通过 Janus 激酶/信号转导子和转录激活子 (JAK/STAT) 途径抑制新生大鼠海马星形胶质细胞中谷氨酸-天冬氨酸转运蛋白和胶质纤维酸性蛋白的表达
DOI：
10.1213/ane.0000000000001238
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发表时间：
2016-07
影响因子：
5.7
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Wang, Wei;Lu, Rui;Feng, Da-yun;Zhang, Hui
背景：全麻诱导神经毒性的机制尚不清楚。星形胶质细胞被认为是神经元发育的重要贡献者。到目前为止，星形胶质细胞对新生儿全麻暴露的反应尚未报道。方法：出生后第7天大鼠接受2.5%七氟醚治疗6小时。在吸入七氟醚后的第1,3,7和14天检测胶质纤维酸性蛋白（GFAP）和谷氨酸-天冬氨酸转运蛋白（GLAST）的表达以及Janus激酶/信号转导和转录激活因子（JAK/STAT）通路的磷酸化。此外，将培养的星形胶质细胞暴露于2.5%七氟醚中2小时，评估GFAP、GLAST表达和JAK/STAT磷酸化。此外，我们在体内用JAK/STAT抑制剂AG490处理，在体外用JAK抑制剂I处理，从药理学上破坏JAK/STAT信号通路，以检测GFAP和GLAST的表达。结果：七氟醚暴露后1 ~ 14天，与假对照组相比，七氟醚诱导海马组织GFAP和GLAST表达明显下降。免疫组化显示GFAP、GLAST和pSTAT3在海马CA1区共定位。Western blot分析也显示pJAK1、pJAK2和pSTAT3在七氟醚组中显著降低。体外研究表明，七氟醚处理后24 ~ 48小时，培养的星形胶质细胞中GFAP、GLAST、pJAK1、pJAK2和pSTAT3的表达显著降低。AG490或JAK抑制剂I均可显著降低海马或培养星形胶质细胞中GFAP和GLAST的表达。结论：七氟醚可抑制新生大鼠海马星形细胞GLAST。JAK/STAT通路的失活可能与七氟醚的这种作用有关。七氟醚引起的星形细胞功能障碍可能导致其对发育中的大脑的神经毒性。
BACKGROUND:The mechanisms underlying general anesthesia-induced neurotoxicity are unclear. Astrocytes have been recognized as important contributors to neuronal development. Until now, the response of the astrocytes to neonatal general anesthetic exposure has been unreported. METHODS:Postnatal day 7 rats received 2.5% sevoflurane for 6 hours. Expressions of glial fibrillary acidic protein (GFAP) and glutamate-aspartate transporter (GLAST) and phosphorylation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway were detected on days 1, 3, 7, and 14 after sevoflurane inhalation. In addition, cultured astrocytes were exposed to 2.5% sevoflurane for 2 hours and GFAP, GLAST expressions, and JAK/STAT phosphorylation were evaluated. Furthermore, we pharmacologically disrupted JAK/STAT signaling in vivo by treatment with the JAK/STAT inhibitor AG490 and in vitro by treatment with JAK inhibitor I to detect the consequent expression of GFAP and GLAST. RESULTS:Sevoflurane induced a robust decrease of GFAP and GLAST expression in hippocampal tissue compared with sham control groups at 1 to 14 days after sevoflurane exposure. Immunohistochemistry showed colocalization of GFAP, GLAST, and pSTAT3 in the hippocampal CA1 region. Western blot analysis also revealed a significant decrease of pJAK1, pJAK2, and pSTAT3 in the sevoflurane group. In vitro study showed that GFAP, GLAST, pJAK1, pJAK2, and pSTAT3 expressions in cultured astrocytes were remarkably decreased at 24 to 48 hours after sevoflurane treatment. Either AG490 or JAK inhibitor I significantly decreased expressions of GFAP and GLAST in hippocampus or cultured astrocytes. CONCLUSIONS:Astrocytic GLAST was inhibited by sevoflurane in the hippocampus of neonatal rats. Inactivation of the JAK/STAT pathway possibly contributes to this effect of sevoflurane. Astrocytic dysfunction induced by sevoflurane may contribute to its neurotoxicity in the developing brain.
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影响因子：
34.7
作者：
Clarke, Laura E.;Barres, Ben A.
通讯作者：
Barres, Ben A.
影响因子：
3.7
作者：
Hong S;Song MR
通讯作者：
Song MR
DOI：
10.1124/jpet.301.1.1
发表时间：
2002-04
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
U. Sonnewald;H. Qu;M. Aschner
通讯作者：
U. Sonnewald;H. Qu;M. Aschner
DOI：
--
发表时间：
2005-09
期刊：
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
影响因子：
--
作者：
Z. Karwacki;P. Kowiański;J. Dziewiątkowski;B. Domaradzka-Pytel;B. Ludkiewicz;S. Wójcik;O. Narkiewicz;J. Morys
通讯作者：
Z. Karwacki;P. Kowiański;J. Dziewiątkowski;B. Domaradzka-Pytel;B. Ludkiewicz;S. Wójcik;O. Narkiewicz;J. Morys
神经病理性疼痛大鼠模型中含有 NR2B 的 NMDA 受体介导脊髓星形细胞 c-Jun N 末端激酶激活
影响因子：
15.1
作者：
Wang, Wei;Mei, Xiao-Peng;Li, Yun-Qing
通讯作者：
Li, Yun-Qing