一氧化氮合酶激活参与烧伤后Ca^(2+)介导的心肌线粒体损伤

Involvement of mtNOS in the Ca^(2+)-induced damages of myocardial mitochondria during the early stage after severe burns

目的 :探讨线粒体一氧化氮合酶 (mtNOS)在严重烧伤早期心肌线粒体损害中的作用。方法 :复制30 %TBSAⅢ°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)及细胞色素c氧化酶、mtNOS活性。结果 :①伤后 1h心肌线粒体呼吸控制率 (RCR)显著高于正常组 ,但 3、6、12、2 4h明显低于正常组 ,Ⅲ态呼吸速率 (ST3 )变化与RCR平行 ,ST4 仅于伤后 3h明显升高 ;②伤后各时点 [Ca2 + ]m 均明显高于正常组 ,尤以 3、6h为甚 ,而mtNOS活性于伤后 3、6、12、2 4h显著高于对照组 ,细胞色素c氧化酶活性于伤后 3、6、12、2 4h显著低于正常组 ;③伤后mtNOS活性与 [Ca2 + ]m 呈明显正相关 ,相关系数为 0 8945 (P <0 0 5 ) ,RCR与mtNOS活性呈显著负相关 ,相关系数为 - 0 934 7(P <0 0 5 )。结论 :伤后 [Ca2 + ]m 升高激活mtNOS ,可能参与严重烧伤早期心肌线粒体损害。

AIM: To study the role of mitochondrial nitric oxide synthase (mtNOS) in the damages of myocardial mitochondria during the early stage after severe burns.METHODS: An experimental model of 30% TBSA full-thickness skin scalding was reproduced in rats. Myocardial mitochondria were isolated from control and burned rats at 1, 3, 6, 12 and 24 h postburn. The mitochondrial respiratory function, content of mitochondrial calcium([Ca 2+ ] m) and activities of mtNOS and cytochrome c oxidase were determined. RESULTS: (1) Myocardial mitochondrial respiratory control rate(RCR) at 1 h was evidently higher than that of control, but at 3, 6, 12 and 24 h postburn, it was significantly lower than that of the control. The changes in ST 3 is parallel to those of RCR, and ST 4 was evidently increased only at 3 h postburn. (2) [Ca 2+ ] m was higher at all time points postburn and the activity of mtNOS was higher significantly only at 3, 6, 12 and 24 h than that of the control. The activity of cytochrome c oxidase at the 3, 6, 12 and 24 h was low comparing to the control. (3) After severe burns, RCR was negatively correlated with mtNOS activity( r=0.9347, P<0.05 ) and mtNOS activity was positive correlated with [Ca 2+ ] m ( r=0.8945, P<0.05 ).CONCLUSION: The elevation of [Ca 2+ ] m significantly activates mtNOS, which might play an important role in the damages of myocardial mitochondria during the early stage after burn injury. [