吸入麻醉药七氟醚对脊髓痛觉传导的双向作用研究

发布时间：2018-04-16 22:17

本文选题：吸入麻醉药 + 七氟醚　；参考：《中南大学》2014年硕士论文

【摘要】：目的通过观察七氟醚对脊髓痛觉传导标记物p-CREB (phosphor-ylated cAMP response element binding protein,磷酸化环腺苷酸反应元件结合蛋白)表达的影响,初步探讨吸入麻醉药七氟醚的镇痛和痛觉过敏双向作用及可能机制。方法本研究以成年雄性SD大鼠作为研究对象,采用行为学分析、免疫组化和Western Blot的方法：①通过足底皮下注射1%福尔马林建立炎性痛痛模型,观察福尔马林注射后不同时间点脊髓内p-CREB的表达变化,以及七氟醚对福尔马林所致炎性痛中脊髓p-CREB表达的作用；②直接观察单纯吸入七氟醚麻醉后脊髓p-CREB表达的变化；③通过在七氟醚麻醉下足底皮下注射低浓度福尔马林并维持麻醉至注射后1h并随后撤去麻醉,建立七氟醚撤药模型,观察七氟醚撤药对0.5%低浓度福尔马林注射后2h和3h的同侧机械性缩足阈值(PWT)和注射后3h的脊髓p-CREB表达的作用。结果①七氟醚对福尔马林诱发的炎性痛中脊髓p-CREB表达的作用：足底注射福尔马林后出现快速的双侧脊髓内p-CREB(免疫组化：P0.001; Western Blot:P0.001)表达明显增多,并在注射后10min达到顶峰,注射后1h双侧脊髓内p-CREB表达下降但明显高于正常水平(免疫组化：P0.001；Western Blot:P0.001);七氟醚麻醉能抑制福尔马林注射后1h脊髓内p-CREB的表达(免疫组化：P0.001; Western Blot:P0.05)。 ②单纯七氟醚麻醉后脊髓p-CREB表达的变化：单纯吸入七氟醚能诱发大鼠双侧脊髓p-CREB的表达(免疫组化：P0.001; Western Blot: P0.001),随着麻醉时间延长而逐渐增多。 ③七氟醚撤药对低浓度福尔马林注射后PWT和脊髓p-CREB表达的作用：七氟醚撤药能诱发低浓度福尔马林注射后2h和3h大鼠PWT下降,并激活低浓度福尔马林注射后3h脊髓p-CREB表达(免疫组化：P0.001; Western Blot:P0.01)。结论七氟醚对脊髓内p-CREB表达具有双向调节作用：七氟醚麻醉能抑制炎性痛中p-CREB表达；而单纯七氟醚麻醉能激活p-CREB表达。此外七氟醚撤药能诱发炎性痛大鼠的痛觉过敏并激活脊髓p-CREB。这些提示七氟醚可能具有痛敏和镇痛的双向作用,并可能导致术后痛觉过敏,这些都可能由p-CREB介导。
[Abstract]:Objective to investigate the effect of sevoflurane on the expression of p-CREB phosphor-ylated cAMP response element binding, a phosphorylated cyclic adenylate responsive element binding protein, in the spinal cord.To explore the two-way effects of sevoflurane on analgesia and hyperalgesia and its possible mechanism.Methods in this study, adult male Sprague-Dawley rats were used to establish inflammatory pain model by subcutaneous injection of 1% formalin into the plantar of Sprague-Dawley rats by behavioral analysis, immunohistochemistry and Western Blot.To observe the changes of p-CREB expression in spinal cord at different time points after formalin injection and the effect of sevoflurane on spinal cord p-CREB expression in formalin induced inflammatory pain.3The model of sevoflurane withdrawal was established by subcutaneous injection of low concentration formalin under sevoflurane anesthesia and maintenance of anesthesia until 1 hour after injection and then withdrawal of anesthesia.To observe the effects of sevoflurane withdrawal on ipsilateral mechanical foot contraction threshold at 2 and 3 hours after injection of 0.5% low concentration formalin and the expression of p-CREB in spinal cord at 3 h after injection.Results 1the effect of sevoflurane on the expression of p-CREB in the spinal cord of formalin-induced inflammatory pain: the expression of p-CREBin in bilateral spinal cord increased rapidly after formalin injection (immunohistochemistry: P0.001; Western Blot: P0.001), and 10min reached its peak after injection.1 h after injection, the expression of p-CREB in the bilateral spinal cord decreased but was significantly higher than the normal level (immunohistochemistry: P0.001 / Western Blot: P0.001) and sevoflurane anesthesia inhibited the expression of p-CREB in the spinal cord 1 h after injection of formalin (immunohistochemistry: P0.001; Western Blot: P0.05).2 changes of p-CREB expression in spinal cord after sevoflurane anesthesia alone: the expression of p-CREB in bilateral spinal cord was induced by sevoflurane alone (immunohistochemistry: P 0.001; Western blot: P 0.001), and increased with the prolongation of anesthesia time.3 the effect of sevoflurane withdrawal on the expression of PWT and p-CREB in spinal cord after low concentration formalin injection: sevoflurane withdrawal induced the decrease of PWT in rats at 2 h and 3 h after low concentration formalin injection.The expression of p-CREB in spinal cord was activated 3 hours after injection of low concentration formalin (immunohistochemistry: P0.001; Western Blot: P0.01a).Conclusion sevoflurane has a bidirectional regulatory effect on the expression of p-CREB in spinal cord: sevoflurane anesthesia can inhibit the expression of p-CREB in inflammatory pain and sevoflurane anesthesia alone can activate the expression of p-CREB.In addition, sevoflurane withdrawal could induce hyperalgesia and activate p-CREB in spinal cord of inflammatory pain rats.These results suggest that sevoflurane may have a two-way effect of pain sensitivity and analgesia, and may lead to postoperative hyperalgesia, which may be mediated by p-CREB.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614

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