控制性低血压对兔脊髓不同节段前角神经元HIF-1α和Caspase-3表达的影响
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摘要
目的观察控制性低血压对兔不同节段脊髓前角神经元HIF-1α和Caspase-3表达的影响。方法 24只健康雄性新西兰白兔随机均分为假手术对照组和控制性低血压组,用硝普钠调控的低血压水平构建兔脊髓缺血缺氧性损伤模型,Western blot检测各种动物脊髓颈、胸、腰节段HIF-1α和Caspase-3蛋白含量,TUNEL染色检测不同节段脊髓前角神经元的凋亡状况。结果 CH组颈、胸、腰段脊髓组织HIF-1α和Caspase-3的表达水平以及TUNEL染色的细胞凋亡指数均明显升高于Cont组相应脊髓节段(P<0.01)。在CH组内,颈段脊髓组织HIF-1α的表达水平低于胸腰段脊髓(P<0.05),而其Caspase-3蛋白的表达水平以及细胞凋亡指数则明显高于胸、腰段脊髓(P<0.01)。结论控制性低血压水平明显导致各节段脊髓组织的缺血缺氧性损伤,且HIF-1α的表达与Caspase-3呈反相关;颈髓的损伤程度比胸、腰段脊髓严重,可能与颈段脊髓对缺血缺氧的敏感性有关。
Objective The study observed the effect of controlled hypotension on the expression of HIF-1α and Caspase-3in spinal cord anterior horn neurons of different segments. Methods Twenty-four adult male New Zealand White rabbitswere randomly divided into sham control(Cont) group and controlled hypotension(CH) group(n=12), and in CH group spinal cord hypoxicischemia injury(SCHII) was induced by sodium nitroprusside. Western blot assayed HIF-1α and Caspase-3 protein expression in cervical, thoracic and lumbar segments of spinal cord. The apoptotic index of spinal cord anterior horn neurons was evaluated with TUNEL staining. Results The expression of HIF-1α and Caspase-3 were obviously higher in cervical, thoracic and lumbar segments of spinal cord in CH group than that in Cont group(all P<0.01). In CH group, the cervical segment of spinal cord has an up-regulated expression of HIF-1α compared with thoracic and lumbar segments of spinal cord(P<0.05), but it has a down-regulated expression of Caspase-3(P<0.01). Conclusion Controlled hypotension could remarkably induce all segments of SCHII. The expression of HIF-1α presented the inverse correlation with Caspase-3, and then the degree of cervical segment injury was more serious than thoracic and lumbar segments in spinal cord, which was possibly associated with the susceptibility of cervical spinal cord to ischemia and hypoxia.
Objective The study observed the effect of controlled hypotension on the expression of HIF-1α and Caspase-3in spinal cord anterior horn neurons of different segments. Methods Twenty-four adult male New Zealand White rabbitswere randomly divided into sham control(Cont) group and controlled hypotension(CH) group(n=12), and in CH group spinal cord hypoxicischemia injury(SCHII) was induced by sodium nitroprusside. Western blot assayed HIF-1α and Caspase-3 protein expression in cervical, thoracic and lumbar segments of spinal cord. The apoptotic index of spinal cord anterior horn neurons was evaluated with TUNEL staining. Results The expression of HIF-1α and Caspase-3 were obviously higher in cervical, thoracic and lumbar segments of spinal cord in CH group than that in Cont group(all P<0.01). In CH group, the cervical segment of spinal cord has an up-regulated expression of HIF-1α compared with thoracic and lumbar segments of spinal cord(P<0.05), but it has a down-regulated expression of Caspase-3(P<0.01). Conclusion Controlled hypotension could remarkably induce all segments of SCHII. The expression of HIF-1α presented the inverse correlation with Caspase-3, and then the degree of cervical segment injury was more serious than thoracic and lumbar segments in spinal cord, which was possibly associated with the susceptibility of cervical spinal cord to ischemia and hypoxia.
引文
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11 李花,邓常清,陈北阳,等.三七总皂苷对大鼠脑缺血再灌注后Caspase表达的影响[J].中国药理学通报,2006,22(2):189-193.
12 Liu Y,Ye H,Satkunendrarajah K,et al.A self-assembling peptide reduces glial scarring,attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury[J].Acta Biomater,2013,9(9):8075-8088.
2 Ha TN,van Renen RG,Ludbrook GL,et al.The effect of blood pressure and cardiac output on the quality of the surgical field and middle cerebral artery blood flow during endoscopic sinus surgery[J].Int Forum Allergy Rhinol,2016,6(7):701-709.
3 Liu B,Zhou D,Huang H,et al.Experimental study on the effect of controlled hypotension levels on rabbit CA1neurons[J].J Surg Res,2013,182(1):e15-24.
4 Kaelin WG Jr,Ratcliffe PJ.Oxygen sensing by metazoans:the central role of the HIF hydroxylase pathway[J].Mol Cell,2008,30(4):393-402.
5 李娜,梁亚统,刘冰冰,等.红花黄色素对硝普钠控制性低血压兔脑组织缺氧诱导因子-1α及Caspase-3表达的影响[J].实用医学杂志,2016,32(9):1404-1407.
6 Lee M,Lee E,Kim Y,et al.Ischemic injury-specific gene expression in the rat spinal cord injury model using hypoxiainduciblesystem[J].Spine,2005,30(24):2729-2734.
7 刘林,薛文,钱耀文.缺氧诱导因子-1α在大鼠脊髓缺血再灌注损伤中的表达[J].中华神经外科疾病研究杂志,2013,12(1):16-19.
8 Dai Y.Preconditioning and post-treatment with cobalt chloride in rat model of perinatal hypoxic-ischemic encephalopathy[J].Brain Dev,2014,36(3):228-240.
9 Yang Y.Changes in levels of hypoxia-induced mediators in rat hippocampus during chronic cerebral hypoperfusion[J].Neurochem Res,2013,38(11):2433-2439.
10 Baranova O.Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia[J].J Neurosci,2007,27(23):6320-6332.
11 李花,邓常清,陈北阳,等.三七总皂苷对大鼠脑缺血再灌注后Caspase表达的影响[J].中国药理学通报,2006,22(2):189-193.
12 Liu Y,Ye H,Satkunendrarajah K,et al.A self-assembling peptide reduces glial scarring,attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury[J].Acta Biomater,2013,9(9):8075-8088.