环维黄杨星-D对脑缺血损伤的保护作用

【作者】 沈祥春；

【导师】 方泰惠；

【作者基本信息】 南京中医药大学 ， 药理学， 2001， 硕士

【摘要】 脑血管疾病是老年人的常见病、多发病，是严重危害老年人健康长寿的疾病之一，其发病率、患病率，均居各类疾病之首。缺血性脑血管疾病的治疗多以恢复再灌为主，但缺血一定时间后再灌注会引起再灌注损伤，因此开发具有防治缺血再灌注损伤的药物具有重要的临床实用价值和社会经济价值。本文主要通过对微循环的影响、对小鼠脑缺血再灌注损伤的影响以及对培养神经细胞的影响三个方面探讨环维黄杨星-D的作用。 1．对微循环的影响：通过在体微循环实验研究环维黄杨星-D对正常小鼠耳廓微循环和家兔球结膜微循环的影响、家兔急性微循环障碍模型以及大鼠急性微循环障碍模型，观察环维黄杨星-D对微动脉（A）、微静脉（V）、微动脉/微静脉（V/A）以及微循环血流速度、对线离流的改善作用。结果表明，环维黄杨星D具有扩张微动脉，减小V/A值，改善线离流、加快急性微循环障碍的血流速度；提示其具有改善微循环的作用。 环维黄杨星-D在10.0mg.kg^-1和20.0mg.kg^-1剂量组均可明显扩张小鼠耳廓细动脉和细静脉的管径，与生理盐水组比较差异显著。但对血流速度未见有明显影响。环维黄杨星-D各剂量组对正常家兔眼球结膜微循环血流明显加快。环维黄杨星-D各剂量组均可以扩张细静脉（p＜0.05、p＜0.01）；4.0mg.kg^-1、8.0mg.kg^-1 币直申口拓大守 ％级硕士学位论文 对细动脉具有明显的扩张作用。环维黄杨星I三个剂量组对急性不完全脑缺血 所致的微循环障碍的微血流速度减慢具有明显的改善作用。环维黄杨星 千．kg’、4mg．kg‘剂量组对急性不完全脑缺血所致微循环障碍时微动脉管径 收缩具有明显的改善作用。同时，实验结果提示环维黄杨星十对微循环的影响 具有种属差异。 2．对脑缺血再灌注的影响：急性脑缺血再灌注小鼠的学习反应潜伏期明显 延长、错误次数增多、记忆潜伏期缩短，错误次数也增多，说明缺血再灌小鼠 学习和记忆功能显著下降；与假手术组比较脑指数、脑含水量及脑湿重明显增 加，LDH、SOD活性明显下降，MDA、NO的含量明显增加。环维黄杨星－D 5 mg．kg‘、 10ms．k合‘显著减少学习过程中潜伏期及错误次数，但环维黄杨星I 20m谷 k合‘ 未见有明显的改善作用；环维黄杨星o sins．k合’、10m巳k合‘剂量组可以明显降 低缺血再灌的脑指数、脑含水量以及脑湿重，差异显著；20m百kg’未见有明显 改善作用；环维黄杨星－D 10mg．kg－‘对SOD、LDH、MDA、NO的含量均具有不同程 度的改善作用，环维黄杨星－D 20ms．ks’对 SOD指标具有一定的改善作用，环维 黄杨星－D sins．ks‘对LDH具有一定的改善作用。 3．对H。0。、GIU、缺糖缺氧诱发的原代培养神经细胞的影响：H。oz、GIU、缺 糖缺氧对原代培养神经细胞均可引起LDH、NOS的活性明显提高、NO、MDA的含 量明显增加。环维黄杨星－D 20X10ed可以明显改善比几所致原代神经细胞损伤的 LDH活性增加以及降低MDA的含量，提示环维黄杨星0对比，所致的原代神经细 胞的损伤具有一定的保护作用。环维黄杨星－D 10X10－‘、20X10’剂量组均可以 明显降低GIU引起的LDH的外漏，环维黄杨星－D 20X10“明显降低GIU引起的 WIA的含量增加；环维黄杨星－D 20X10“明显降低 GIU所致原代培养皮层细胞的 NO含量的升高，降低NOS的活力。环维黄杨星－D 10X10”、20X10”剂量组均可 以明显降低缺糖缺氧所致 LDH的外漏，环维黄杨星－D 20X10As明显降低缺糖缺氧 引起的 WIA、NO含量及 NOS的活性的增加，环维黄杨星个三剂量组均可以明显 －2－ 币亥申＠历走一 咒馒硕士 论文 降低LDH的活牲，环维黄杨星－DI OX10ed明显降低MDA、NO的含量，20X10As明显 降低 NOS的活力，环维黄杨星－D10X10一、20X10As对缺血缺糖损伤所致的细胞死 亡率具有保护作用。更多还原

【Abstract】 CBV-D has been recorded by Chinese Phamacopoeia. The effects of CBV-D on cerebral ischemia reperfusion were studied in this artiele.This dissertation consists of three patrs. Part 1. Effect of CBV-D on micro-circulation: The effect of CVB-D was studied from the following aspects: experiment of micro-circulation on the auricle of mice, rabbit conjunctiva aperture of and obstruction of meninges micro-circulation of rats induced by urgent in-complete ischemia. The results showed that CVB-D could dilate micro-artery and micro-vena, improve line and particle flow. Therefore, the CBV-D can markedly improved micro-circulation. CBV-D dilate micro-artery and micro-vena on auricle of mice administrated 10mg. kg-1, 20. 0mg. kg-1 by 1. g, once a day for three day. However there isn?t marked influence on flow of blood. But it could markedly increase both flow velocity of blood and flow velocity of blood induced by Dextran T500 conjunctiva of aperture on rabbit; l0mg.kg?20.Omg.kg CBV-D can markedly dilate micro-artery. The decreased flow velocity of blood induced by urgent non-complete ischemia on rats can increase, simultaneously improve contractions on meninges micro-artery. Simultaneity , the results shows that effects of CBV-D on micro-circulation are diffenent to varsity. Part 2 Effect of CBV-D against cerebral ischemia-reperfusion injury in mice: On the cerebral ischemia-reperfusion model mice, the levels of MDA,NO and the activity of NOS were increased, but the activity of LDH were decreased, and the water content of brain ,index of brain and the wet weight of brain were increased. 5 mg. kg-1 10mg. kg1CBV-D could improve the learning and memory capability of model mice in step down test, but there were not markedly improve at the dosage of 20mg. kg CBV-D.5mg. kg-1、10mg. kg-1CBV-D could markedly decreased index of brain, water content of brain and wet weight of brain, 2Omg.kg-1CBV-D could not markedly. 10mg.kg-1CBV-D could markedly improved SOD, LDH, MBA and NO. 20mg. k&tCBV-D could markedly improve SOB, however 5mg.kg-1CBV-D could markedly improve LDH. Part3. Protective effects on H2O2-induced ,Glu-induced and ischemic injury in culturing rat cortical neurons: The efflux of LDH of neurons, content of MBA, NO in neurons and activity of NOS were increased by H202-induced ,Glu-induced and ischemic injury in culturing rat cortical neurons. 2OX1O-1 CBV-D could markedly reduced the effux of LDH and content of MBA, which results showed that CBV-D had perfect effect on 1-1202-induced cultured rat cortical neurons. To Glu-induced in cultured rat cortical neurons, 1OXlO-1 CBV-D and 2Oy10-1 CBV-D could markedly reduce the effux of LDH and content of MBA, 20/lW CBV-D could markedly reduce activity of NOS and content of NO. To ischemic injury in cultured rat cortical neurons, three groups of CBV-D could markedly reduce the effux of LDH; 20/lW CBV-D could markedly reduce activity of NOS, content of NO and content of MBA. iO-1iW CBV-D could markedly reduced content of NO and content of MDA. 20/lW CBV-D could markedly reduced activity of NOS. Both iOyiW CBV-D and20/1W CBV-D can reduce the cell death ratio.更多还原