复方血栓通胶囊防治缺血性中风的实验研究

发布时间：2018-04-21 21:26

本文选题：复方血栓通胶囊 + 缺血性中风　；参考：《广州中医药大学》2014年硕士论文

【摘要】：目的：采用线栓法制作大鼠大脑中动脉缺血再灌注损伤模型,在此基础上评价复方血栓通胶囊防治缺血性中风的作用,并对其作用机理进行探讨,为复方血栓通胶囊临床应用于缺血性中风提供药理学依据。方法：本实验将雄性SD大鼠随机分为假手术组、模型组、尼莫地平组、脑安胶囊组、复方血栓通低(0.375g/kg)、中(0.75g/kg)、高(1.5g/kg)剂量组,灌胃给药,每天一次,连续7天。末次给药1h后,腹腔注射10%水合氯醛麻醉大鼠,将线栓从颈总动脉缓缓插入颈内动脉,直达大脑中动脉的起始部,阻断同侧大脑中动脉所有血供来源。2h后,将线栓缓缓拔出进行再灌注。假手术组除不插入线栓外,其余操作与手术组相同。术后10h重复灌胃给药1次。采用Berderson评分法观察造模后4h、10h、24h大鼠神经行为。再灌注后24h后,用PowerLab生物电放大系统记录大脑脑电活动；取脑切片,用TTC染色后,ImageJ软件分析脑梗死面积比；称量动物体质量,取全脑,称脑湿重与干重,计算脑组织含水量；取脑组织,HE染色,光镜下观察脑细胞形态。为进一步研究其保护机制,采用激光多普勒仪检测大脑皮层血流量；测定血清中TXA2、PGI2、ET-1及CGFP的含量；测定脑组织中Glu、MDA、NO、Lac、 Pyru、LDH的含量。结果：实验结果表明,与假手术组比较,模型组大鼠的神经行为评分在缺血再灌注4h、10h、24h后均显著升高；脑电活动平均波幅显著降低；脑梗死面积显著增大；脑含水量明显升高；病理评分分值有增加趋势,神经组织坏死及细胞结构破坏严重。与模型组相比,复方血栓通低、中、高剂量组大鼠在缺血再灌注4h、10h、24h的神经行为评分显著降低；血栓通低、中、高剂量组大鼠脑电活动平均波幅显著增大；复方血栓通低、中、高剂量组大鼠脑梗死面积显著减少；复方血栓通中、高剂量组大鼠脑含水量显著减少；复方血栓通低、中、高剂量对SD大鼠脑组织病理评分有所降低,但无显著性差异；进一步的机制研究显示,模型组与假手术组比较,脑微循环血流量显著减少,血清中TXA2、ET-1含量显著升高,PGI2、CGRP含量显著降低,TXA2/PGI2比值显著增大；脑组织中Glu、MDA、NO、Lac、LDH、LPR值含量均显著升高。与模型组相比,血栓通低、中、高剂量组大鼠脑微循环血流量显著增加；血栓通低剂量组大鼠血清TXA2含量显著降低；血栓通高剂量组PGI2含量显著升高；血栓通低剂量组TXA2/PGI2的比值显著减小；血栓通低剂量组大鼠血清ET-1含量明显降低；血栓通低、中剂量组CGRP含量显著升高；血栓通低、中、高剂量组MDA与NO含量显著降低；血栓通高剂量组大鼠脑组织Glu、Lac、LDH含量、LPR值均显著降低。结论：复方血栓通胶囊对缺血再灌注损伤具有明显的保护作用,其保护机制可能与改善脑内微循环、抗自由基损伤、拮抗兴奋性氨基酸毒性作用和改善能量代谢有关。实验结果为复方血栓通胶囊应用于缺血性中风的预防和治疗提供了药理学依据。
[Abstract]:Purpose :

The model of ischemia - reperfusion injury in the middle cerebral artery of rats was made by using the method of thread embolism . On the basis of this , the effect of Fufang Xuetong capsule on ischemic stroke was evaluated and the mechanism of its action was discussed . It provided the pharmacological basis for the clinical application of Fufang Xuesong capsule in ischemic stroke .

Method :

In this experiment , male SD rats were randomly divided into sham operation group , model group , nimodipine group , Naoan capsule group , compound thrombus low ( 0.375g / kg ) , middle ( 0.75g / kg ) and high ( 1.5g / kg ) dose group .

After 24 hours of reperfusion , the brain electrical activity was recorded with a PowerLab bioelectrical amplification system after 24 hours of reperfusion .
Brain slices were taken and stained with TTC and the area ratio of cerebral infarction was analyzed by ImageJ software .
weighing dynamic object quality , taking whole brain , weighing brain wet weight and dry weight , and calculating brain tissue water content ;
Brain tissue and HE staining were taken and the morphology of brain cells was observed under light microscope .

In order to further study its protective mechanism , the cerebral cortex blood flow was detected by laser Doppler instrument .
The contents of TXA2 , PGI2 , ET - 1 and CGFP in serum were measured .
The contents of Glu , MDA , NO , Lac , Pyru and LDH in brain tissue were measured .

Results :

The experimental results showed that the neurobehavioral score of the model group increased significantly after 4 h , 10 h and 24 h after ischemia / reperfusion compared with the sham operation group .
The average amplitude of EEG decreased significantly .
the area of cerebral infarction increased significantly ;
the water content of brain increased obviously ;
The scores of pathological scores increased , the necrosis of nerve tissue and the destruction of cell structure were serious .

Compared with the model group , the neurobehavioral scores of the rats in low , medium and high dose groups were significantly decreased at 4 h , 10 h and 24 h after ischemia / reperfusion .
The average amplitude of brain electrical activity increased significantly in low , medium and high dose groups .
The cerebral infarction area of the rats with low , medium and high doses was significantly reduced .
The cerebral water content of rats with high - dose group was significantly decreased in compound thrombus .
The pathological score of the brain tissue of SD rats was decreased , but there was no significant difference between them .

The results showed that the cerebral microcirculation blood flow was significantly decreased , the contents of TXA2 and ET - 1 in serum were significantly increased , the contents of PGI2 and CGRP decreased , and the ratio of TXA2 / PGI2 increased significantly compared with sham operation group .
The content of Glu , MDA , NO , Lac , LDH and Lpr in brain tissue was significantly increased .

Compared with the model group , the cerebral microcirculation blood flow in the middle and high dose groups increased significantly in the middle and high dose groups .
The content of TXA2 in serum of low - dose group was significantly lower than that in low - dose group .
The content of PGI2 in the high - dose group was significantly higher than that in the high - dose group .
The ratio of TXA2 / PGI2 in the low - dose group was significantly decreased .
The content of ET - 1 in serum of low - dose group was significantly lower than that in low - dose group .
The content of CGRP in middle - dose group was significantly higher than that in middle - dose group .
The content of MDA and NO in the middle and high dose groups were significantly lower than those in the middle and high dose groups .
The content of Glu , Lac , LDH in brain tissue of the rats with high - dose thrombus was significantly decreased .

Conclusion :

Compound Xuesong capsule has obvious protective effect on ischemia - reperfusion injury , and its protective mechanism may be related to improving microcirculation , free radical damage , antagonism of excitatory amino acid toxicity and improving energy metabolism . The experimental results provide pharmacological basis for the prevention and treatment of ischemic stroke .

【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R285.5

【参考文献】