山茶花总黄酮对实验性心肌缺血的保护及其机制
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摘要
山茶花总黄酮(Total flavone of Camellia,TFC)是从山茶花中提取的有效部位。近年来,多种黄酮类化合物经研究证实对缺血性心肌损伤有保护作用,但TFC对心肌缺血保护作用的研究还未见报道。本研究在多种心肌缺血动物模型上观察了TFC对心肌缺血的保护作用,并对其可能机制进行了初步探讨,主要研究结果如下:
     1、TFC延长气管挟闭小鼠心电持续的时间
     在气管挟闭小鼠心肌缺氧模型上,TFC(80,40mg·kg~(-1),ig)可明显延长气管挟闭小鼠心电持续的时间。
     2、TFC减轻垂体后叶素(Pituitrin,Pit)诱发的大鼠心肌缺血性损伤
     在舌下静脉注射(intravenous injection,iv)Pit诱发大鼠心肌损伤模型上,TFC(60,30mg.kg~(-1),ig)能明显抑制iv Pit后ST段的上移和T波的抬高,降低血清和心肌组织中丙二醛(malondiadehyde,MDA)含量,同时降低血清中乳酸脱氢酶(lactate dehydrogenase,LDH)的活力。
     3、TFC减轻异丙肾上腺素(Isoproterenol,Iso)诱发的大鼠心肌缺血性损伤
     在皮下注射(Subcutaneous injection,Sc)Iso诱发大鼠心肌损伤模型上,TFC(60,30mg.kg~(-1),ig)可明显改善缺血心肌的病理损伤程度,刺激心肌组织中热休克蛋白70(Heat shock protein 70,Hsp70)的表达,升高血清中超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione Peroxidase,GSH-PX)的活力,降低组织中的MDA含量,钙离子浓度,同时增强心肌组织中腺苷三磷酸(Adenosine triphosphate,ATP)酶的活力。
     4、TFC减轻大鼠血栓的湿重,抑制大鼠动静脉血栓的形成
     在大鼠动静脉血栓形成实验中,与NS组相比,TFC(60,30mg.kg~(-1),ig)可明显减轻血栓的湿重。
     5、TFC抑制胶原和腺苷二磷酸(Adenosine diphosphate,ADP)诱导的血小板聚集
    
    安徽医科大学硕士学位论文
     在胶原和ADP诱导的体外血小板聚集实验中,TFc(l .0,0.5,0.25mg.ml一,)可明
    显抑制加入胶原和ADP Zmin及smin时的血小板聚集。
    6、TFC减轻结扎冠状动脉左前降支(anterior deseending of the left arter丫LAD)家兔
    心肌缺血性损伤
     在冠状动脉左前降支(LAD)结扎致家兔心肌缺血损伤模型上,TFC(60,
    3Omg.kg一,,19)能明显减少家兔心肌梗死面积,降低冠脉结扎后6h及24h时ST段
    的抬高,降低血清中肌酸激酶(ereatine kinase,CK)的活力和内皮素(endo伍etin,ET)
    的含量,升高血清中一氧化氮(nitric oxide,N0)的浓度。
     结论:TFC对心肌缺血缺氧损伤有明显的保护作用,其机制可能与减轻细胞膜
    脂质过氧化、改善心肌细胞能量代谢、抑制血小板聚集、抗血栓形成、保护血管
    内皮细胞等有关。
Total flavone of Camellia (TFC) is the effective part, which was extracted from the flower of Camellia. Recently many kinds of flavones from plants have been investigated to have protective effects on myocardial ischemia injury. Till now total flavone of Camellia hasn't been reported to have such effects. In this paper, the protective effect of TFC on myocardial ischemia injury and its mechanism were studied. Results were showed as followed:
    1. TFC 80, 40 mg.kg"' remarkedly prolonged the ECG time after clamping trachea on the myocardial anoxia model induced by clamping trache in mice.
    2. On the myocardial ischemia model induced by Pituitrin in rats, TFC 60, 30 mg.kg-1 can ameliorate the changes of ST height and T wave; TFC 60,30,15mg.kg-1 significantly reduced the MDA contents in the myocardium and serum of rats; TFC 30 mg.kg "'reduced the activity of LDH in the serum of rats.
    3. On the myocardial ischemia model induced by isoproterenol in rats, TFC 30 mg.kg "'reduced the MDA and calcium contents and increased the activity of ATPase in the myocardium of rat; TFC 30,15mg.kg-1 increased the activity of SOD in the serum of rats; TFC 60,30mg.kg-1 increased the activity of GSH-PX in the serum of rats.
    4. On the myocardial ischemia model induced by isoproterenol in rats, it was found that the density of distribution of Hsp70 was significantly elevated in TFC 60,3 0,15mg.kg-1 groups. That is to say, Hsp70 was positively expressed.
    5. On the myocardial infarction model by occluding the anterior descending of the left artery (LAD) in rabbits, TFC 60,30mg.kg-1 obviously reduced the height of ST segment after occlusion 6h, 24h, the activity of CK and the content of ET in the serum of rabbits after occlusion 24h; TFC 60mg.kg-1 also obviously reduced the the size of myocardial ischemia.
    
    
    6. TFC 60,30mg.kg-1 obviously decrease the wet weight of thrombosis on the A-V thrombosis pass-by model.
    7. TFC1.0, 0.5, 0.25mg.ml-1 has magnificent effect on inhibition of platelet aggregation in vitro.
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