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Effects of adenosine receptor antagonist on spinal neuronal injury after transient spinal cord ischemia.

腺苷受体拮抗剂对短暂性脊髓缺血后脊髓神经元损伤的影响。

基本信息

批准号：
08671758
负责人：
TAIRA Yutaka
金额：
$ 0.77万
依托单位：
University of the Ryukyus
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671758/
关键词：
spinal cord ischemia rat paraplegia hypotension adenosine theophylline プロペントフィリン

项目摘要

To examine the role of adenosine receptor on spinal neuronal injury after transient spinal cord ischemia, following expeniments were performed.1. Estimation of the rat spinal aid ischemia modeL : Motor function of hind limbs of the rats, which suffered different duration of aortic occlusion, were observed for 72 hours 100% (8/8) of the rats, of which aorta were occluded for 10 mm, showed complete paraplegia. Though the rats, of which aorta were occluded for 6 mm, showed transient and slight motor weakness of hind limb, all of them (7/7) recovered to normal walk.2. Effects of adenosine receptor agonist and antagonist on spinal neuronal injury after transient spinal aid iachemia :Intrathecal injection of theophylline, an adenosine receptor antagonist, (100 mug) did not worsen the motor function after 6 min spinal cord ischemia model Intrathecal injection of propentofylline, an adenosine re-uptake inhibitor, (30 mug or 100 mug) did not improve the motor deficit after 10 min spinal cord ischenia Intrathecal injection of 2-chroloadenosina a selective adenosine Al receptor agonist, (10 mug of 30 mug) did not improve the motor deficit after 10 min spinal cord ischemia.3. Effect of on glutamate concentration in lumbar cerebral spinal fluid after 10 min spinal cord ischemia : Though 2-chroloadenosme did not reduce the concentration of glutamate till 3 hours after reperfusion, reduced significantly at 4 hours alter reperfusion.Our results indicated that adenosine receptor activation reduced the glutamate concentration in CSF, but, it would not have significant role in the mechanism of spinal ischemic neuronal injury in the model in which spinal collateral blood flow was reduced by proximal hypotension. Also it was suggested that protective effect of adenosine receptor activation reported previously may be due to vasodilation by adenosine A2 receptor activation.

为了研究腺苷受体在短暂性脊髓缺血后脊髓神经元损伤中的作用，进行了以下实验。大鼠脊髓辅助缺血模型的评价：观察不同时间的主动脉阻断大鼠后肢运动功能，72h后100%(8/8)的大鼠出现完全性截瘫。结论：1.大鼠主动脉阻断6 mm后，虽然出现一过性轻度后肢运动无力，但全部(7/7)恢复正常行走。腺苷受体激动剂和拮抗剂对短暂性脊髓缺血后脊髓神经元损伤的影响：鞘内注射腺苷受体拮抗剂茶碱(100杯)对脊髓缺血6分钟后的运动功能没有恶化作用；鞘内注射腺苷再摄取抑制剂丙戊茶碱(30或100杯)不能改善脊髓缺血10分钟后的运动功能障碍；鞘内注射选择性腺苷Al受体激动剂2-铬负荷肌苷(10杯30杯)不能改善脊髓缺血10分钟后的运动障碍。对脊髓缺血10min后腰脑脊液中谷氨酸浓度的影响：2-羟色胺在再灌流后3h才能降低脑脊液中谷氨酸的浓度，再灌流后4h明显降低。结果表明，在近端降压减少脊髓侧支血流量的模型中，腺苷受体激活降低了脑脊液中的谷氨酸浓度，但在脊髓缺血性神经元损伤的机制中没有明显作用。另外，以前报道的腺苷受体激活的保护作用可能是通过激活腺苷A2受体来扩张血管的。