一氧化氮合酶调节伤段脊髓血流量的作用及其机制

The regulation effect of nitric oxide synthase on blood flow and mechanism of injured spinal cord

目的 探讨一氧化氮合酶 (NOS)在脊髓损伤早期调节伤段脊髓血流量的作用及其机制。 方法 通过大鼠脊髓伤前 30min蛛网膜下腔注射NOS底物左旋精氨酸 (L -Arg)及其不同剂量的抑制剂亚硝基左旋精氨酸甲酯 (L -NAME) ,采用激光多普勒血流仪观测不同NOS活性状态对伤段脊髓血流量的影响 ;同时应用免疫组化和酶标免疫电镜技术 ,进一步研究NOS在脊髓组织中的分布规律及其调节血流量的超微结构特征。 结果 伤前注射L -Arg导致伤段脊髓伤后早期血流量明显改善 ;而注射不同剂量的抑制剂则导致剂量依赖性血流量降低。参与脊髓血流量调节的NOS主要是位于神经细胞胞浆内的Ⅰ型。 结论 NOS在脊髓损伤早期伤段脊髓血流量的调节中起着极其关键的作用 ;许多含有NOS的神经细胞和其突起与脊髓微血管毗邻的解剖学结构确保了半衰期极短的一氧化氮 (NO)在其丧失活性之前作用于微血管 。

Objective To explore the mechanism and the regulation effect of nitric oxide synthase (NOS) on injured spinal cord blood flow (SCBF) in the early period of spinal cord injury. Methods Larginine (a substrate for the formation of NO) and different doses of LNAME (an inhibitor of NOS) were infused into the spinal subrachnoid space 30 minutes before spinal cord injury (SCI). Then, the effect of different activities of NOS on SCBF at the injured sites was monitored by LaserDoppler flowmetry; meanwhile,the derivation and characteristics of NOS was investigated by immunohistochemistry and immunoelectronmicroscopy. Results The intrathcal injection of Larginine increased early SCBF at the injured sites; and LNAME resulted in dosedependent SCBF decrease. NOS in normal spinal cord,especially NOSⅠ was identified in the cytoplasm of neurons. Many neural processes and neurons containing NOS were closely associated with spinal cord microvessels. Conclusions NOS plays a key role in regulating the early SCBF at the injured sites by NO synthesis. The ultrastructural features and many neural processes and neurons containing NOS help NO with short halflife effect microvesseles and regulat microcirculation before lose of activities.