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Effects of Xingnaojing Injection on Adenosinergic Transmission and Orexin Signaling in Lateral Hypothalamus of Ethanol-Induced Coma Rats

机译:醒脑静注射液对乙醇致昏迷大鼠下丘脑腺苷能传递和食欲素信号的影响

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摘要

Acute alcohol exposure induces unconscious condition such as coma whose main physical manifestation is the loss of righting reflex (LORR). Xingnaojing Injection (XNJI), which came from Chinese classic formula An Gong Niu Huang Pill, is widely used for consciousness disorders in China, such as coma. Although XNJI efficiently shortened the duration of LORR induced by acute ethanol, it remains unknown how XNJI acts on ethanol-induced coma (EIC). We performed experiments to examine the effects of XNJI on orexin and adenosine (AD) signaling in the lateral hypothalamic area (LHA) in EIC rats. Results showed that XNJI reduced the duration of LORR, which implied that XNJI promotes recovery form coma. Microdialysis data indicated that acute ethanol significantly increased AD release in the LHA but had no effect on orexin A levels. The qPCR results displayed a significant reduction in the Orexin-1 receptors (OX1R) expression with a concomitant increase in the A1 receptor (A1R) and equilibrative nucleoside transporter type 1 (ENT1) expression in EIC rats. In contrast, XNJI reduced the extracellular AD levels but orexin A levels remained unaffected. XNJI also counteracted the downregulation of the OX1R expression and upregulation of A1R and ENT1 expression caused by EIC. As for ADK expression, XNJI but not ethanol, displayed an upregulation in the LHA in EIC rats. Based on these results, we suggest that XNJI promotes arousal by inhibiting adenosine neurotransmission via reducing AD level and the expression of A1R and ENT1.
机译:急性酒精暴露会引起昏迷状态,例如昏迷,昏迷的主要物理表现是扶正反射丧失(LORR)。醒脑静注射液(XNJI)来自中国经典配方安宫牛黄丸,在中国广泛用于昏迷等意识障碍。尽管XNJI有效地缩短了急性乙醇诱导的LORR的持续时间,但仍不清楚XNJI如何作用于乙醇诱导的昏迷(EIC)。我们进行了实验,以检查XNJI对EIC大鼠下丘脑外侧区(LHA)中的orexin和腺苷(AD)信号传导的影响。结果显示,XNJI减少了LORR的持续时间,这意味着XNJI促进了昏迷的恢复。微透析数据表明,急性乙醇可显着增加LHA中的AD释放,但对食欲素A水平无影响。 qPCR结果显示EIC大鼠中Orexin-1受体(OX1R)的表达显着减少,同时A1受体(A1R)和1型平衡核苷转运蛋白(ENT1)的表达随之增加。相比之下,XNJI降低了细胞外AD水平,但orexin A水平未受影响。 XNJI还抵消了由EIC引起的OX1R表达下调以及A1R和ENT1表达上调。至于ADK的表达,XNJI而不是乙醇在EIC大鼠的LHA中显示出上调。根据这些结果,我们建议XNJI通过降低AD水平以及A1R和ENT1的表达来抑制腺苷神经传递来促进唤醒。

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