缺氧复合氰化纳中毒对大鼠脑组织线粒体影响

Functional variation of mitochondria in rat brain injured by hypoxia and/or NaCN intoxication

目的探讨缺氧和氰化物中毒2种因素对大鼠脑线粒体能量储备和线粒体复合体抑制的作用。方法雄性SD大鼠分为平原组、高原急性缺氧组和阶梯适应组。各组大鼠进行相应的处理后,腹腔注射氰化钠3.6mg/kg,于中毒0,0.5和2h时相点麻醉,断头取脑,提取脑组织线粒体蛋白。高效液相色谱分析大鼠脑线粒体腺苷三磷酸(ATP)、腺苷二磷酸(ADP)和腺苷一磷酸(AMP)含量。常规比色法测定线粒体呼吸链复合体Ⅰ和Ⅳ的活性。结果平原组、高原缺氧组和阶梯适应组氰化钠中毒脑内线粒体ATP的含量降低,ADP和AMP的含量增加(P<0.05或P<0.01);线粒体复合体Ⅰ和Ⅳ的活性降低,与对照组比较差异有统计学意义(P<0.01);高原缺氧组与相应的平原组比较脑内线粒体ATP的含量降低(P<0.05),ADP和AMP的含量增加(P<0.05)。结论氰化钠中毒可加重急性高原缺氧导致的脑组织线粒体内腺苷酸能量代谢储备障碍和线粒体复合体Ⅰ和Ⅳ活性抑制。

Objective To explore the function variation of mitochondria in the rat brain injured by acute hypobaric hypoxia and/or NaCN intoxication. Methods Adult SD rats （male） were divided randomly into normoxic group, acute hy- poxia group and pre-step adaptation group. The acute hypoxic exposure model was established by exposing the rats to a hy- pobaric chamber simulating 4 000 m above sea level for 3 days. The rats in the pre-step adaptation group were continuously exposed to hypobaric chamber stimulating 1 500,2 500,3 000, 3 500 and 4 000m ,respectively for one day. The rats were in- jected with 3.6mg/kg NaCN intra-peritoneally. The rats were sacrificed and the brains were isolated at the time of 0. 5 and 2h of intoxication. Brain mitochondria were isolated by centrifugation program. HPLC was employed to determine the con- tents of ATP, ADP and AMP in the mitochondria of the rat brain. Results In normoxic group, acute hypoxia group and pre- step adaptation group ,ATP content was decreased and ADP and AMP contents were inereased（ P 〈0.05 or P 〈0.0I ）. The activities of mitochondrial complex I and Ⅳ were also decreased. ATP of the acute hypoxia group decreased. ADP and AMP contents were increased compared to these of the normoxic group （ P 〈 0. 05 ）. Conclusion NaCN intoxication may influence the energy store reduction and the activity of complex Ⅰ and Ⅳ of the brain mitochondria in rats exposed to acute hypoxia.