权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

ROLE OF NITRIC OXIDE IN PATHOGENESIS UNDERLYING ISCHEMIC BRAIN DAMAGE

一氧化氮在缺血性脑损伤发病机制中的作用

基本信息

批准号：
05671181
负责人：
MATSUI Toru
金额：
$ 1.34万
依托单位：
SAITMA MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671181/
关键词：
Nitric oxide nitric oxide synthase brain ischemia nitro-L-arginine brain edema infarction

项目摘要

The present study aimed at examining whether ischemic brain damage might develop mediated via a postischemic overproduction of nitric oxide in the brain tissue.First, concentration of nitric oxide in the rat brain was directly measured, using newly devised microsensor. The exaggerated production (ca. 2-3 mumol) of nitric oxide was appeared in the affected hemisphere 15-20 minutes after MCAo and then reversed to the baseline. Three hours after MCAo, nitric oxide was yielded again over the baseline. The preischemic administration of LNA (Nomega-nitro-L-arginine, 1mg/kg, It is already reported that this dose is effective for prevention of ischemic brain edema following MCAo in rats) inhibited both of the above phenomena and ischemic brain edema was significantly blocked. Second, from the chronological study of Ca2^+-dependent and -independent NOS activity of cerebral MVs obtained from the affected hemisphere of the MCAo rats, Ca2^+-dependent NOS was first activated 10 times more than its … More baseline value immediately after MCAo. At 4 hours after MCAo, Ca2^+-independent NOS (9 times of the baseline value, p<0.01 vs.control) was siginifcantly activated (p<0.01 vs.control). At 48,168 hr after MCAo, in place of Ca2^+-independent, Ca2^+-dependent NOS was activated again (3 times of the baseline value, p<0.01 vs.control).Third, effects of LNA on brain water content subjected to MCAo was examined. it was elucidated that repeated intraperitoneal injection of 0.01 to 1mg/kg LNA found to be effective for prevention of increase in brain water content, 72 hours after MCAo.The present study suggested that the ischemic brain is always subjected to high-concentrated nitric oxide, yielded from cerebral MVs and that adequate inhibition of both type of NOS in cerebral MVs by LNA might be beneficial for prevention of ischemic brain edema. The present study provided the first evidence that two distinct types of NOSs were activated and involved in the pathogenesis of ischemic brain damage and that a total inhibition of NOS is not required. Less

本研究的目的是探讨缺血性脑损伤是否可能通过脑组织中一氧化氮的过度产生介导。首先，使用新设计的微传感器直接测量大鼠脑中一氧化氮的浓度。夸张的生产（CA。2-3 MCAo后15-20分钟，患侧大脑半球出现一氧化氮（nitric oxide），然后恢复到基线水平。MCAo后3小时，一氧化氮再次超过基线。缺血前给予LNA（N-硝基-L-精氨酸，1 mg/kg，已报道此剂量对预防大鼠MCAo后缺血性脑水肿有效）可抑制上述两种现象，并显著阻断缺血性脑水肿。第二，从MCAo大鼠患侧大脑MVs的Ca 2 ^+依赖性和非依赖性NOS活性的时间顺序研究中发现，Ca 2 ^+依赖性NOS首先被激活的时间是其激活时间的10倍。 ...更多信息 MCAo后即刻的基线值。在MCAo后4小时，Ca 2 ^+非依赖性NOS（基线值的9倍，p<0.01 vs.control）显著激活（p<0.01 vs.control）。在MCAo后48、168小时，Ca 2 ^+依赖性NOS再次激活，而非Ca 2 ^+依赖性NOS激活（是基线值的3倍，p<0.01 vs.control）。结果表明，反复腹腔注射0.01 ~ 1 mg/kg LNA可有效地防止MCAo后72小时脑含水量的增加。本研究表明，缺血脑始终处于高浓度的一氧化氮，结论：LNA能有效抑制脑MVs中两种NOS的表达，对缺血性脑损伤的预防可能是有益的水肿本研究提供了第一个证据表明，两种不同类型的NOS被激活，并参与缺血性脑损伤的发病机制，并认为NOS的总抑制是不需要的。少