高迁移率族蛋白B1预处理对大鼠脊髓缺血再灌注损伤的影响

Effects of high mobility group box 1 preconditioning on spinal cord ischemia reperfusion injury in rats

摘要:

目的：评价高迁移率族蛋白B1（high mobility group box 1，HMGB1）预处理对大鼠脊髓缺血再灌注损伤（spinal cord is－chemia reperfusion injury，SCII）的影响。方法：健康成年雄性SD大鼠于缺血前18 h经侧脑室给予不同浓度的重组HMGB1预处理。采用Zivin改进法建立大鼠SCII模型，阻断腹主动脉45 min后行再灌注。于再灌注6、12、24 h取血清检测循环中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6 （interleukin-6，IL-6）水平，取脊髓组织检测核因子-κB（nuclear factor-κB，NF-κB）活性及其抑制蛋白（inhibitors κB-α，IκB-α）含量。评价大鼠后肢运动神经功能，观察脊髓组织病理学改变。结果：再灌注各时间点，与行单纯缺血再灌注损伤的大鼠相比，给予HMGB1预处理后大鼠后肢运动神经功能评分明显提高，脊髓前角正常运动神经元的计数增多，血清中TNF-α、IL-6水平下降，脊髓组织中IκB-α含量增高，NF-κB活性降低。结论：HMGB1预处理对大鼠SCII具有保护作用，其机制与预处理减少IκB-α降解，抑制NF-κB活性，从而减轻炎性反应有关。

Abstract:

Objective：To investigate the effects of high mobility group box 1（HMGB1） preconditioning on spinal cord ischemia reper－fusion injury（SCII） in rats. Methods：Various concentrations of HMGB1 were injected into lateral ventricle of male SD rats at 18 h before ischemia. SCII model was completed by clamping the abdominal aorta for 45 min according to modified Zivin. At 6，12，24 h after reperfusion，blood samples were collected to measure the levels of tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） and the spinal cord segment was harvested to detect the activity of nuclear factor-κB（NF-κB） and expression of inhibitor κ B-α（IκB-α）. Meanwhile，functional evaluation on hind limbs was done and pathological change of spinal cord was observed. Results：Preconditioning with HMGB1 significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons，which was accompanied with reduction of levels of TNF-α and IL-6 in serum as well as degradation of IκB-α and activity of NF-κB in spinal cord. Conclusions：Preconditioning with HMGB1 protects spinal cord against ischemia-reperfusion injury by at－tenuating inflammatory response.