二氮嗪对严重烧伤大鼠心肌损害的保护作用及其机制

Protective effects of diazoxide on cardiomyocytes after severe burn injury and the related mechanism

目的 探讨二氮嗪对严重烧伤早期心肌损害的保护作用及其机制。方法 健康成年Wistar大鼠 2 4只 ,随机分为正常对照组、烧伤组和烧伤二氮嗪处理组 (n =8)。烧伤组、烧伤二氮嗪处理组大鼠造成 3 0 %TBSAⅢ度烧伤 ,伤后 3 0min经腹腔补液 ,烧伤二氮嗪处理组同时于颈外静脉推注二氮嗪 (剂量 10mg kg)。烧伤组和烧伤二氮嗪处理组动物于伤后 6h抽血并活杀 ,测定线粒体K+ 内流、呼吸功能、Ca2 + 浓度 ( [Ca2 + ]m)、MDA及血清LDH、CK。结果 二氮嗪处理组线粒体K+ 内流速率明显高于正常组与烧伤组 ,且线粒体呼吸控制率 (RCR)、Ⅲ态呼吸速率 (ST3)明显高于烧伤组 ,而 [Ca2 + ]m、MDA含量显著低于烧伤组 ,Ⅳ态呼吸速率 (ST4 )与正常对照组无显著差异 ;同时二氮嗪处理组血清CK、LDH显著低于烧伤组 ,分别是烧伤组的 63 7%和 5 2 0 %。结论 二氮嗪可减轻严重烧伤早期心肌细胞损害 ,其机制可能与开放线粒体K+ 通道 ,抑制线粒体Ca2 +

Objective To investigate the protective effects of diazoxide on cardiomyocytes after severe burn injury Methods A total of 24 healthy Wistar rats were randomized into normal control group(Control), burn group(Burn) and diazoxide treated group(Diazo)( n =8) Rats in Burn and Diazo groups were inflicted with 30%TBSA Ⅲ degree burn and resuscitated with Ringer's solution intraperitoneally 30 min after burn Diazoxide was injected into rats in Diazo group at the dose of 10 mg/kg through the external jugular vein After rats were sacrificed at 6 h after burn, myocardial mitochondrial K + influx, respiratory function, Ca 2+ concentration ([Ca 2+ ]m), MDA content, serum CK and LDH levels were determined Results Mitochondrial K + influx of Diazo group was evidently higher than that in Control and Burn group Mitochondrial respiratory control rate(RCR) and ST 3 in Diazo group were higher than that in Burn group However, [Ca 2+ ]m, MDA, CK and LDH levels in Diazo group were significantly lower than those in Burn group Conclusion Diazoxide can attenuate the damage to cardiomyocytes after severe burn injury, which might be related to the opening of mitochondrial K + channel, inhibition of mitochondria from Ca 2+ overloading and decrease of free radical production