Effects of dexmedetomidine combined with targeted temperature management on the expression of hippocampal P2X7 receptor and antisense hypoxia inducible factor-1α in rats with traumatic brain injury

Shih-Wei Li, Fan Li, Yi-dan Huang, Xu-Hong Wei
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Abstract

Objective To investigate the effects of dexmedetomidine (Dex) combined with targeted temperature management (TTM) on the expression of hippocampal P2X7 receptor and antisense hypoxia inducible factor (aHIF)-1α in rats with traumatic brain injury (TBI). Methods A model of TBI was established through controlled cortical impact using rats after 1 week of adaptive feeding. Then, 15 rats were randomly selected as a control group, while the others were set as a model group. The successfully modeled rats were divided into five groups (n=15), according to the random number table method: a sham operation group, a TBI group, a TBI+Dex group, a TBI+TTM group and a TBI+Dex+TTM group. After corresponding treatment, their behaviors were tested, and the expression of tumor necrosis factor (TNF)-α/interleukin (IL)-1β in brain tissue and the expression of hippocampal P2X7 receptor and aHIF- 1α were analyzed. Results Rats in each group did not die. Compared with the TBI, TBI+Dex and TBI+TTM groups, the TBI+Dex+TTM group presented remarkably reduced escape latency on Days 3-5 and shortened exploration duration on Day 6 (P<0.05), as well as decreased expression of TNF-α and IL-1β in brain tissues (P<0.05), reduced expression of hippocampal P2X7 receptor and increased amounts of aHIF- 1α (P< 0.05). Conclusions Dex combined with TTM can effectively decline the concentration of P2X7 receptor, down-regulate the levels of TNF-α and IL-1β, and increase the level of aHIF- 1α, which can be served as a promising therapy for TBI rats. Key words: Brain injuries, traumatic; Dexmedetomidine; Targeted temperature management; P2X7 receptor; Antisense hypoxia inducible factor- 1α
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右美托咪定联合靶向温度管理对创伤性脑损伤大鼠海马P2X7受体和反义缺氧诱导因子-1α表达的影响
目的探讨右美托咪定(Dex)联合靶向温度管理(TTM)对创伤性脑损伤大鼠海马P2X7受体和反义缺氧诱导因子(aHIF)-1α表达的影响。方法适应性喂养1周后,采用控制性皮质冲击法建立大鼠脑外伤模型。然后,随机选取15只大鼠作为对照组,其余大鼠作为模型组。将成功造模的大鼠按随机数字表法分为5组(n=15):假手术组、TBI组、TBI+Dex组、TBI+TTM组和TBI+Dex+TTM组。治疗后检测各组小鼠行为,分析脑组织肿瘤坏死因子(TNF)-α/白细胞介素(IL)-1β的表达、海马P2X7受体和aHIF- 1α的表达。结果各组大鼠均未死亡。与TBI、TBI+Dex和TBI+TTM组比较,TBI+Dex+TTM组小鼠3 ~ 5天的逃避潜伏期明显缩短,第6天的探查时间明显缩短(P<0.05),脑组织中TNF-α、IL-1β表达明显降低(P<0.05),海马P2X7受体表达明显降低,aHIF- 1α表达明显升高(P<0.05)。结论右美托咪唑联合TTM可有效降低P2X7受体浓度,下调TNF-α、IL-1β水平,升高aHIF- 1α水平,有望成为治疗TBI大鼠的有效方法。关键词:脑损伤;外伤性;Dexmedetomidine;针对性温度管理;P2X7受体;反义缺氧诱导因子- 1α
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