目的 研究伏立诺他在无静脉补液条件下对致死性烫伤大鼠生存率和心脏功能的影响。方法 建立50%TBSAIII°烫伤大鼠模型，60只雄性SD大鼠随机分为假烫组（n=12）：37℃水浴浸泡，烫伤组（n=24）：伤后腹腔内注射0.25ml生理盐水，SAHA组(n=24)：伤后腹腔内注射SAHA（7.5mg/kg，溶于0.25ml 0.9%生理盐水）。伤后观察6h，各组取8只大鼠，取腹主动脉血测血浆CK-MB、TNF-α水平，处死动物取心肌组织，采用伊文斯蓝( EB) 染色法检测心脏组织血管通透性，caspase-3活性试剂盒测定心肌组织内caspase-3活性，Western blot测定心肌组织内HIF-1α、iNOS、BNIP3蛋白表达水平；各组剩余大鼠观察12h生存率。结果 烫伤组伤后12小时内全部死亡，给与SAHA处理后12h生存率为50%，大鼠存活时间明显延长，与烫伤组比较有统计学意义（P<0.05）；与假烫组比较，烫伤组伤后CK-MB水平、血管通透性、TNF-α含量、caspase-3活性明显升高，HIF-1α及iNOS、BNIP3蛋白表达明显增加（P均<0.05）；而给与SAHA处理后，CK-MB水平、血管通透性、TNF-α含量、caspase-3活性明显下降，HIF-1α及iNOS、BNIP3蛋白表达明显降低，比较均具有统计学意义（P均<0.05）。结论 在无液体复苏条件下，SAHA能延长致死性烫伤大鼠生存时间，保护心脏功能，降低心脏血管通透性，其作用机制可能与其减轻全身炎症反应、降低caspase-3活性，抑制HIF-1α及下游靶基因iNOS、BNIP3的表达有关。

Objective To investigate the effect of suberoylanilide hydroxamic acid(SAHA) on survival and cardiac function in rats with fatal scald without fluid resuscitation. Methods Resulting in third degree scald injury involving 50% TBSA，60 male SD rats of clean-level, they were randomly divided into 3 groups:the sham scald group（n=12）、the scald group（n=24）、the SAHA group（n=24）.Rats in scald group and SAHA group were subjected to 50％TBSA third-degree full-thickness scald injury with boiled water，respectively，they received an intraperitoneal injection of 0.25ml of 0.9% normal saline（NS）or SAHA (7.5mg/kg,dissolved in 0.25ml of NS) .And 37℃ water instead of boiled water was used for the rats in sham scald group.At 6h after scald,8 rats in each group were select ,blood in each group was with drawn from the abdominal aorta to detect the level of creatine kinase isoenzymes（CK-MB） and TNF-α,the rats were sacrificed and collected cardical tissues.Visceral microvascular permeability was examined with evans ,the activity of caspase-3 was measured by detection kits,the expression of HIF-1α、iNOS、BNIP3 were detected by Western blot assay. Results The survival rate of the SAHA group was 50% at 12 h, which significantly prolonged the survival time of rats, while all died at 12 h after injury in the scald group, and the difference was statistically significant (P < 0.05).Compared with the sham group, the levels of CK-MB、visceral microvascular permeability、the level of TNF-α、the content of caspase-3、the protein expression levels of HIF-1α、iNOS、BNIP3 were significantly increased（P all<0.05）;however, after SAHA treatment, tthe levels of CK-MB、visceral microvascular permeability、the level of TNF-α、the content of caspase-3、the protein expression levels of HIF-1α、iNOS、BNIP3 were significantly reduced compared with the scald group(P all< 0.05).Conclusions:Without fluid resuscitation,SAHA can prolong the survival time,protect the cardiac function and reduce the visceral microvascular permeability of rats with fatal scald,the mechanism may be related to the reduction of systemic inflammatory response、the decrease of caspase-3 activity、the inhibition of HIF-1αand the downstream target genes iNOS、BNIP3.

国家自然科学基金项目（面上项目，重点项目，重大项目）