摘要
目的利用心肌梗死后心力衰竭模型研究组织激肽释放酶(TK)和缓激肽(BK)改善心功能、抑制心肌纤维化的机制。方法冠状动脉结扎后1周,纯化的TK及BK连续皮下渗透给药4周,5周后处死动物。导管法检测各组动物的心功能,天狼红染色检测胶原的沉积,银染法测量心肌细胞的面积,免疫组织化学法检测Ⅰ、Ⅲ型胶原,W estern b lot-ting检测TGF-β1、Sm ad 2和phosph-Sm ad 2的表达,化学发光法检测一氧化氮(NO)和过氧化物的含量。结果TK及BK能明显改善心功能,对梗死面积无影响。治疗组胶原的沉积明显减少,细胞肥大减轻,TGF-β1、Smad的表达和磷酸化减少,NO的合成增加,过氧化物蓄积减轻。结论TK及BK对心肌梗死后的心力衰竭有治疗作用,抑制TGF-β1活化及过氧化物形成是主要的机制。
Objective We investigated the effects of tissue kallikrein （TK） and bradykinin （BK） on cardiac function and fibrosis in rats after myocardial infarction （MI）. Methods At 1 week after coronary artery ligation, rats were infused with TK or BK via osmotic minipumps for 4 weeks. At 5 weeks after MI, hemodynamic parameters were analyzed. We used sirius red staining for collagen deposition, immunostaining for collagen Ⅰ, Ⅲ and silver staining for cardiomyocyte size. Nitric oxide （NO） and malondialdehyde levels were measured by chemiluminesence. Western blotting was used to examine TGF-β1, Smad 2 and the phosphorylation of Smad 2. Results TK and BK infusion significantly improved cardiac function with no apparent effect on infarct size. TK and BK infusion inhibited interstitial collagen deposition and reduced cardiomyocyte size,TGF-β1 expression,Smad 2 and Smad 2 phosphorylation. The effects of TK and BK on cardiac remodeling were associated with increased cardiac NO and reduced malondialdehyde levels. Conclusions These results indicate that TK or BK can restore impaired cardiac function, inhibit hypertrophy and fibrosis through increasing NO formation,suppressing oxidative stress and TGF-β1 expression.
出处
《现代医学》
2008年第6期393-396,共4页
Modern Medical Journal
