Ca^(2+)介导严重烧伤早期心肌线粒体呼吸功能损害

Calcium induced the damage of myocardial mitochondrial respiratory function in the early stage after severe burns

目的 :探讨Ca2 + 在严重烧伤早期心肌线粒体呼吸功能损害中的作用及其机制。方法 :复制 30 %TBSAⅢ度烧伤大鼠模型 ,取正常及伤后 1、3、6、12、2 4h大鼠心肌分离线粒体 ,测其呼吸功能、Ca2 + 浓度 ([Ca2 + ]m)、F0 F1-ATPase和细胞色素c氧化酶活性 ,同时观察心肌线粒体能量代谢变化。结果 :①伤后 1h [Ca2 + ]m 即明显升高 ,同时心肌线粒体呼吸功能加强 ,呼吸控制率(RCR)、Ⅲ态呼吸速率升高 ,且RCR与 [Ca2 + ]m 呈显著正相关 (r=0 .8415 ,P <0 .0 1) ;伤后 3、6、12、2 4h心肌 [Ca2 + ]m 升高更加明显 ,但线粒体呼吸功能反而下降 ,RCR与 [Ca2 + ]m 均呈显著负相关。②F0 F1-ATPase活性于伤后 1h明显降低 ,但 3h显著高于对照组 ,6、12、2 4h再度下降 ;伤后 3、6、12、2 4h线粒体细胞色素c氧化酶活性分别下降 42 .5 %、36 .2 %、32 .3%和 18.9%。③大鼠烧伤后 1h心肌线粒体ATP含量无明显变化 ,但 3、6、12、2 4h线粒体ATP含量均显著降低 ,同时ADP含量升高。结论 :烧伤初始 [Ca2 + ]m 适度升高 ,促进线粒体呼吸功能加强 ;烧伤后续阶段Ca2 + 严重超载在线粒体呼吸功能损害中起重要作用。

Objective: To explore the role of Ca 2+ in the damages of myocardial mitochondrial respiratory function in the early stage after severe burns.Methods: Myocardial mitochondria were isolated from control and burned rats(30%TBSA full-thickness skin scalded). The mitochondrial respiratory function, contents of mitochondrial calcium( m),ATP, ADP and AMP, activities of F 0F 1-ATPase and cytochrome c oxidase were determined.Results:① m was increased evidently at the first hour postburn, and the myocardial mitochondrial respiratory function was significantly reinforced at the same time. Mitochondrial respiratory control rate (RCR) was elevated and positively relatived with m (r=0.8415, P<0.01). At the 3rd, 6th, 12th and 24th hour, m was increased more evidently. However, the mitochondrial respiratory function was decreased, and RCR was negatively relatived with m. ②The activity of F 0F 1-ATPase was increased at the 3rd hour postburn, but lower than that of the control at the 1st, 6th, 12th and 24th hour. The activity of cytochrome c oxidase decreased 42.5%, 36.2%, 32.3% and 18.9% respectively at the 3rd, 6th, 12th and 24th hour. ③The mitochondrial ATP content didn't change evidently at the 1st hour postburn, but with ADP content increasing, it decreased at the 3rd, 6th, 12th and 24th hour. Conclusion: Appropriate increasement of m reinforces the mitochondrial respiration at the beginning of burns, but Ca 2+ severe overload plays an important role in the damages of myocardial mitochondrial respiratory function in the following stage.