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  本文選題：復(fù)方血栓通膠囊 + 缺血性中風(fēng)�。� 參考：《廣州中醫(yī)藥大學(xué)》2014年碩士論文

【摘要】：目的： 采用線栓法制作大鼠大腦中動脈缺血再灌注損傷模型,在此基礎(chǔ)上評價復(fù)方血栓通膠囊防治缺血性中風(fēng)的作用,并對其作用機理進(jìn)行探討,為復(fù)方血栓通膠囊臨床應(yīng)用于缺血性中風(fēng)提供藥理學(xué)依據(jù)。 方法： 本實驗將雄性SD大鼠隨機分為假手術(shù)組、模型組、尼莫地平組、腦安膠囊組、復(fù)方血栓通低(0.375g/kg)、中(0.75g/kg)、高(1.5g/kg)劑量組,灌胃給藥,每天一次,連續(xù)7天。末次給藥1h后,腹腔注射10%水合氯醛麻醉大鼠,將線栓從頸總動脈緩緩插入頸內(nèi)動脈,直達(dá)大腦中動脈的起始部,阻斷同側(cè)大腦中動脈所有血供來源。2h后,將線栓緩緩拔出進(jìn)行再灌注。假手術(shù)組除不插入線栓外,其余操作與手術(shù)組相同。術(shù)后10h重復(fù)灌胃給藥1次。 采用Berderson評分法觀察造模后4h、10h、24h大鼠神經(jīng)行為。再灌注后24h后,用PowerLab生物電放大系統(tǒng)記錄大腦腦電活動；取腦切片,用TTC染色后,ImageJ軟件分析腦梗死面積比；稱量動物體質(zhì)量,取全腦,稱腦濕重與干重,計算腦組織含水量；取腦組織,HE染色,光鏡下觀察腦細(xì)胞形態(tài)。 為進(jìn)一步研究其保護(hù)機制,采用激光多普勒儀檢測大腦皮層血流量；測定血清中TXA2、PGI2、ET-1及CGFP的含量；測定腦組織中Glu、MDA、NO、Lac、 Pyru、LDH的含量。 結(jié)果： 實驗結(jié)果表明,與假手術(shù)組比較,模型組大鼠的神經(jīng)行為評分在缺血再灌注4h、10h、24h后均顯著升高；腦電活動平均波幅顯著降低；腦梗死面積顯著增大；腦含水量明顯升高；病理評分分值有增加趨勢,神經(jīng)組織壞死及細(xì)胞結(jié)構(gòu)破壞嚴(yán)重。 與模型組相比,復(fù)方血栓通低、中、高劑量組大鼠在缺血再灌注4h、10h、24h的神經(jīng)行為評分顯著降低；血栓通低、中、高劑量組大鼠腦電活動平均波幅顯著增大；復(fù)方血栓通低、中、高劑量組大鼠腦梗死面積顯著減少；復(fù)方血栓通中、高劑量組大鼠腦含水量顯著減少；復(fù)方血栓通低、中、高劑量對SD大鼠腦組織病理評分有所降低,但無顯著性差異； 進(jìn)一步的機制研究顯示,模型組與假手術(shù)組比較,腦微循環(huán)血流量顯著減少,血清中TXA2、ET-1含量顯著升高,PGI2、CGRP含量顯著降低,TXA2/PGI2比值顯著增大；腦組織中Glu、MDA、NO、Lac、LDH、LPR值含量均顯著升高。 與模型組相比,血栓通低、中、高劑量組大鼠腦微循環(huán)血流量顯著增加；血栓通低劑量組大鼠血清TXA2含量顯著降低；血栓通高劑量組PGI2含量顯著升高；血栓通低劑量組TXA2/PGI2的比值顯著減��；血栓通低劑量組大鼠血清ET-1含量明顯降低；血栓通低、中劑量組CGRP含量顯著升高；血栓通低、中、高劑量組MDA與NO含量顯著降低；血栓通高劑量組大鼠腦組織Glu、Lac、LDH含量、LPR值均顯著降低。 結(jié)論： 復(fù)方血栓通膠囊對缺血再灌注損傷具有明顯的保護(hù)作用,其保護(hù)機制可能與改善腦內(nèi)微循環(huán)、抗自由基損傷、拮抗興奮性氨基酸毒性作用和改善能量代謝有關(guān)。實驗結(jié)果為復(fù)方血栓通膠囊應(yīng)用于缺血性中風(fēng)的預(yù)防和治療提供了藥理學(xué)依據(jù)。
[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 .

【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R285.5

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