【作者】 武煜；

【导师】 顾振纶； 谢梅林； 周文轩； 郭次仪；

【作者基本信息】 苏州大学 ， 药理学， 2005， 硕士

【摘要】 目的 观察茶多酚（Tea Polyphenol,TP）对实验性心肌肥厚及心肌细胞损伤的保护作用,并初步探讨其作用机制。方法采用大鼠腹主动脉缩窄（coarctation of abdominal aorta,CAA）及小鼠小剂量异丙肾上腺素（Isopenaline,Iso）连续皮下注射制作心肌肥厚动物模型,观察TP对心肌肥厚是否具有保护作用:建立H₂O₂致心肌细胞损伤模型,观察TP对其的影响;采用RT-PCR法检测心肌组织中与心肌肥厚有关的过氧化物酶体增殖物活化受体α（peroxisome proliferator activated receptors α,PPARα）mRNA的表达。结果 1.TP给药组大鼠心重指数及术后第5周收缩压均低于腹主动脉缩窄组（P<0.05,P<0.01）。TP可明显增加心肌肥厚大鼠血清SOD活性（P<0.01）,减少MDA生成（P<0.05,P<0.01）,抑制血清和心肌FFA堆积（P<0.01）,增加Na⁺-K⁺-ATPase活性（P<0.01）,并可减少羟脯氨酸含量（P<0.01）;病理镜检显示TP组心肌细胞肥大及肌原纤维排列紊乱均有所减轻。电镜分析表明,TP可减轻心肌细胞及线粒体肿胀,减少肌丝溶解断裂。2.TP可改善Iso致小鼠左心室肥厚形成的“老损”征象,降低心重指数（P<0.05,P<0.01）,增加SOD活性（P<0.01）,降低MDA含量（P<0.05,P<0.01）,增加NO含量（P<0.05）,同时降低血清CPK和LDH水平（P<0.05,P<0.01）。3.TP在体外与心肌细胞共孵后可减轻H₂O₂引起的细胞损伤,增加心肌细胞的存活率（P<0.01）,降低LDH释放量（P<0.05,P<0.01）,并可对抗H₂O₂诱发的细胞内[Ca²⁺]i升高（P<0.05,P<0.01）。4.TP可增加腹主动脉缩窄大鼠心肌组织中PPAR α mRNA的表达（P<0.05,P<0.01）。结论 TP能预防实验性大鼠、小鼠心肌肥厚并对乳鼠心肌细胞损伤具有更多还原

【Abstract】 Aim: To investigate the protective effects of Tea Polyphenol （TP） on cardiac hypertrophy and cell injury in cultured myocardium cells. Methods: Cardiac hypertrophy models of rats induced by CAA （coarctation of abdominal aorta） and mice induced by continued administration of Isoprenaline （Iso） were used. The H₂O₂-induced myocardial cell injury in vitro was used as well. RT-PCR was used to determine the expression of PPAR α （peroxisome proliferator activated receptors α ） which is related to cardiac hypertrophy. Results:1. After administration of TP for 5 wks, the cardiac weight indexes and BP were significantly decreased compared with that in the CAA group （P<0.05, P<0.01） , the increase of serum SOD activity and decrease of serum MDA content were found （P<0.05, P<0.01） , the contents of FFA in serum and myocardial tissue were decreased （P<0.01 ） . Also, Na⁺-K⁺-ATPase activity in myocardial tissue was elevated in TP groups （PO.01） . At the same time the hydroxyproline content and the hypertrophic myocardial cells and disorder fibril were reduced and abated respectively after administration of TP （PO.01） . 2.After administration of TP for 2 wks, the ’cardiac hypertrophy fatigue’ which can be seen from the electrocardiograms and the cardiac weight indexes were decreased （P<0.05, P<0.01） . There were an increase in serum SOD activity, a decrease in serum MDA、 LDH、 CPK contents and an increase in NO content （P<0.05, P<0.01） . 3.The injury ofmyocardium cells induced by H2O2 when incubated TP with cells was reduced （P<0.01）, and LDH release, decreased CP<0.05, P<0.0l) . The [Ca2+]i overload induced by H2O2 was prevented by TP （PO.05, PO.01） . 4. TP can elevate the expression of PPAR a mRNA in mycardial tissue CP<0.05, PO.01). Conclusion: TP could inhibit the cardiac hypertrophy in rats and mice and had protective effects on cultured neonatal rat heart cells. These effects of TP were related to scavenging oxygen free radical, decreasing blood pressure, blocking calcium overload, improving the energy metabolism and increasing PPAR a mRNA expression.更多还原