张丽敏,陈凤收,李 哲,陈晓光,马 虹.右美托咪定后处理对脊髓缺血再灌注损伤后Caspase-3、IL-1β的表达和血脊髓屏障的影响[J].,2019,19(11):2013-2018 |
右美托咪定后处理对脊髓缺血再灌注损伤后Caspase-3、IL-1β的表达和血脊髓屏障的影响 |
Effects of Dexmedetomidine Postconditioning on Caspase-3, IL-1β Expression and Blood-spinal Cord Barrier after Spinal Cord Ischemia-reperfusion Injury |
投稿时间:2018-12-26 修订日期:2019-01-30 |
DOI:10.13241/j.cnki.pmb.2019.11.003 |
中文关键词: Caspase-3 IL-1β 右美托咪定后处理 脊髓缺血再灌注损伤 |
英文关键词: Caspase-3 IL-1β Dexmedetomidine postconditioning Spinal cord ischemia-reperfusion injury |
基金项目:国家自然科学基金项目(81771342) |
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中文摘要: |
摘要 目的:研究右美托咪定后处理在大鼠急性脊髓缺血再灌注损伤(spinal cord ischemia-reperfusion injury, SCIRI)后对细胞因子Caspase-3、IL-1β的表达量和血脊髓屏障(blood-spinal cord barrier, BSCB)的影响。方法:将120只成年雄性SD大鼠随机分为5组:假手术组(sham组)、脊髓缺血再灌注组(IR组)、脊髓缺血再灌注右美托咪定低剂量组(DEX1组)、脊髓缺血再灌注右美托咪定中剂量组(DEX5组)、脊髓缺血再灌注右美托咪定高剂量组(DEX10组)。采用改良的Zivin法构建脊髓缺血再灌注损伤模型,实验中应用临床上常用的微量泵泵注的方法对大鼠给予等量生理盐水和右美托咪定,造模24 h后采用Tarlov法对大鼠运动功能评分,伊文思蓝(Evans Blue, EB)染色检测血脊髓屏障通透性,HE染色观察大鼠脊髓病理学变化(L4-L6),western blot检测Cas- pase-3、IL-1β的表达。结果:与sham组比较,IR组及DEX各组下肢运动功能评分明显较低,脊髓结构损伤严重,神经元数目减少,血脊髓屏障渗透性增加,Caspase-3、IL-1β表达量增多;与IR组比较,DEX各组下肢运动功能评分较高,脊髓结构损伤明显减轻,神经元数目增多,血脊髓屏障渗透性减少,western blot显示caspase-3、IL-1β表达降低;与DEX5组比较,DEX1组和DEX10组的下肢运动功能评分较低,脊髓结构损伤较重,神经元数目较少,血脊髓屏障渗透性减少,western blot显示Caspase-3、IL-1β表达增加。结论:右美托咪定后处理对SCIRI具有明显的保护作用,可以保护BSCB的完整性,减轻对脊髓的损失。该保护作用可能与激动α2肾上腺素受体,降低炎症反应中IL-1β表达,下调Caspase-3表达的抗细胞凋亡作用有关。 |
英文摘要: |
ABSTRACT Objective: To study the effects of dexmedetomidine postconditioning on expression of protein Caspase-3 and IL-1β, and blood-spinal cord barrier in rats with spinal cord ischemia-reperfusion injury. Methods: Choose 120 adult male Sprague-Dawley rats, and divide them randomly and evenly into 5 groups: sham group, IR group, DEX1 group, DEX5 group, and DEX10 group. Spinal cord ischemia-reperfusion injury was modelled by adopting the improved Zivin method. Normal saline and dexmedetomidine were injected into the rats with equal quantity with the help of the widely used micro-pump. The motor function of rats was evaluated quantitatively with score by adopting the Tarlov method 24 h after the reperfusion. For measurement of the permeability of blood-spinal cord barrier in spinal cord, the dyeing method with Evans Blue was used. The pathological changes of spinal cord was observed by HE staining, and the expression of protein Caspase-3 and IL-1β was assessed by the western blot. Results: By comparing the sham group and the other groups, it is found that lower extremity motor function score in IR group and DEX groups were much lower, spinal cord structure was damaged seriously, the number of neurons was decreased, the permeability of blood-spinal cord barrier was increased, and the expression of pro- tein Caspase-3 and IL-1β were increased; Further, to compare the IR group and the DEX groups, the results show that lower extremity motor function score in DEX groups were significantly higher, damage of spinal cord structure injury was mitigated, the number of neu- rons was increased, the permeability of blood-spinal cord barrier was decreased, and the expression of protein Caspase-3 and IL-1β de- creased based on results of the western blot; Finally, results of the DEX groups are compared with each other. Among them, the results of DEX1 and DEX10 groups show lower motor function score, more spinal cord injury and fewer neurons, that the permeability of blood-spinal cord barrier was decreased, and that Caspase-3 and IL-1β expression were increased visualized by western blot results. Conclusion: Dexmedetomidine postconditioning has obvious protective effect on SCIRI, which can maintain structure of BSCB and de-crease the damage of spinal cord. This protective effect may work by activating the α2 adrenergic receptor, decreasing IL-1β expres- sion in inflammatory reaction and degrading the anti-apoptotic effect of Caspase-3 expression. |
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