乌龙丹对多梗死性痴呆模型大鼠血液黏度、内皮素及一氧化氮的影响

背景乌龙丹是在长期临床用于缺血性脑血管病治疗中总结出来的经验方,该方以"益气健脾补肾,活血通络化痰"立法.以前的研究表明该方具有改善大脑微循环,调节神经内分泌和抗脑缺血损伤等作用.血液黏度升高,血管及神经细胞等分泌的内皮素、一氧化氮(NO)失调参与了多梗死性痴呆(multi-infarctdementia,ID)病理发展过程,且相互影响.目的通过复制MID大鼠模型,探讨乌龙丹对MID模型大鼠血液黏度、NO及内皮素的影响.设计以实验动物为研究对象的随机对照实验研究.单位一所军医大学的中医系.材料实验于2002-01/08在解放军第一军医大学中医系实验室和附属珠江医院神经内科实验室完成.选用清洁级SD大鼠雄性大鼠,体质量(270±30)g(合格证号2000337).实验分为空白对照组、模型组、乌龙丹低剂量组、乌龙丹高剂量组.方法在分离一侧颈内动脉后,推注1200比例的同种属的大鼠干血悬液0.8mL制作MID大鼠模型.血液黏度测定采用锥板法,内皮素测定采用放射免疫法,O测定采用镉还原比色法,乌龙丹的制剂采用水煮醇提法.主要观察指标主要指标各实验组全血黏度和血浆黏度、血浆内皮素、NO浓度.次要指标学习记忆测试结果.结果模型组大鼠全血黏度(mpa·s)显著升高(200s-17.21±1.02;5s-111.24±0.93,＜0.01),血浆内皮素(ng/L)含量(167.91±46.87,P＜0.01)和内皮素/NO增高(64.94±11.14,＜0.01),O(μmol/L)则下降(2.60±0.43,＜0.01);给药组大鼠全血黏度(mpa·s)与模型组比较差异有显著性意义(高剂量200s-14.28±0.81;5 s-18.84±0.79,P＜0.01;低剂量200 s-15.22±0.92, s-19.18±0.81,＜0.05),血浆内皮素(ng/L)(高剂量120.18±34.51,＜0.01)、NO(μmol/L)含量(6.84±0.79,＜0.01)及内皮素/NO(31.26±8.41,＜0.01)与模型组比较差异均有显著性意义.结论血液黏度升高,血管及神经细胞等分泌的内皮素、NO失调参与了MID病理发展过程,且相互影响.乌龙丹的健脾补肾、活血化痰通络?对MID模型大鼠血液黏度升高、NO和内皮素分泌异常有对抗和调节作用.

Effect of wu long dan on blood viscosity,endothelin and nitric oxide in rat model of multi-infarct dementia

BACKGROUND: Wu long dan is the experienced formula summarized in the long-term clinical practice on the treatment ischemic cerebral vascular disorder and aims at "benefiting qi,strengthening spleen,tonifying kidney,activating blood circulation,promoting circulation of collaterals and resolving phlegm". It is indicated in the previous researches that such formula acts on improving microcirculation of cerebrum,regulating neural endocrinal system and being against cerebral ischemic injury. The increased blood viscosity and disturbance endothelin and nitric oxide(NO) secreted from vessels and nerve cells have participated in the pathological progression of multi-infarct dementia(MID) and affect mutually.OBJECTIVE: To probe into the effect of wu long dan on blood viscosity,NO and endothelin in MID model in rats by duplicating MID rat model.DESIGN: A randomized controlled and experimental study based on the experimental animals.SETTING: Department of traditional Chinese medicine in a military medical university of Chinese PLA.MATERIALS: The experiment was performed in Laboratory of Department of Traditional Chinese Medicine in First Military Medical University of Chinese PLA and Laboratory of Department of Neurological Internal Medicine in affiliated Zhujiang Hospital from January to August 2002. SD male rats of clean grade were employed,weighted(270 ± 30) g (Qualified No. 2000337). In the experiment,there were blank control,model group,wu long dan low dosage group and wu long dan high dosage group.METHODS: After internal carotid artery isolated,dried blood suspension of homologous rats was injected at the ratio of 1:200 to prepare MID rat model. Cone-plate stationary method was adopted for the determination of blood viscosity,radioimmunoassay was for the determination of endothelin and cadmium-reduction-colorimetric method was for NO determination. Water-alcohol sedimentation was for the preparation of wu long dan.MAIN OUTCOME MEASURES: Primary indexes: whole blood viscosity,plasma viscosity,plasma endothelin and NO concentration in every experimental group. Secondary indexes: results of learning and memory test.creased significantly (200 s-1: 7.21 ± 1.02; 5 s-1: 11.24 ± 0.93,P ＜ 0.01 ),the plasma endothelin(ng/L) content(167.91 ±46. 87,P ＜0.01) and endothelia/NO(64.94 ± 11.14,P ＜0.01) were increased,and NO(μmol/L)(2.60 ± 0. 43,P ＜ 0.01 ) reduced. The significant difference in the vismedication group in rats(in high dosage 200 s-1: 4.28 ±0. 81,5 s-1:8.84±0.79,P ＜0.01; in low dosage 200 s-1: 5.22±0.92,5 s-1;9.18 ± 0. 81,P ＜ 0.05 ) with model group. Concerning to plasma endothelin(ng/L) (in high dosage 120. 18±34.51,P ＜ 0.01),NO (μmol/L)content(6.84 ± 0.79,P ＜ 0.01 ) and endothelin/NO(31.26 ± 8.41,P＜ 0.01 ),the significant differences presented in all of those compared with model group.CONCLUSION: The increased blood viscosity and the disturbance between endothelin and NO secreted from vessels and nerve cells have participated in the pathological progression of multi-infarction MID and affect mutually. Wu long dan with the efficacy of strengthening spleen and tonifying kidney,activating blood circulation,resolving phlegm and promoting the circulations of collaterals acts on antagonism and regulation of increased blood viscosity and abnormal secretion of NO and endothelin in MID model rats.