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

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

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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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
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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