去乙酰毛花甙与依那普利拉单用及配伍应用对烫伤大鼠脏器早期损害的影响

Effects of single or combined administration of cedilanid and enalaprilat on visceral damages in early stage of severe scald in rats

目的了解去乙酰毛花甙与依那普利拉单用及两药配伍应用对严重烫伤大鼠心、肝、肾、肠早期损害的影响。方法将40只雄性Wistar大鼠按随机数字表法分为假伤组（模拟烫伤）、烫伤对照组、去乙酰毛花甙组、依那普利拉组、去乙酰毛花甙＋依那普利拉组，每组8只。大鼠麻醉后给予背部30％TBSAm度烫伤，伤后30min腹腔注射乳酸钠林格液（4mL·kg^-1·1％TBSA^-1）复苏治疗。补液同时去乙酰毛花甙组静脉注射去乙酰毛花甙0．2mg／kg；依那普利拉组静脉注射依那普利拉1mg／kg；去乙酰毛花甙＋依那普利拉组静脉注射去乙酰毛花甙及依那普利拉，剂量同前。伤后6h，以多道生理信号采集处理系统记录各组大鼠心肌力学指标；以激光多普勒血流仪记录肝、肾、肠血流量；取大鼠静脉血检测心肌肌钙蛋白I（cTnI）、总胆汁酸（TBA）、β2微球蛋白（β2-MG）、二胺氧化酶（DAO）。结果与假伤组比较，烫伤对照组大鼠各项心肌力学指标均显著降低；肝血流量为（158±32）血流灌注单位（PU）、肾（156±46）PU、肠（119±30）PU，亦显著降低（P〈0．05）；血清cTnI（5．0±0．3）μg／L、TBA（82±23）μmol／L、β2-MG（2．55±0．15）mg／L、DAO（1．52±0．08）kU／L，明显高于假伤组（P〈0．05）。与烫伤对照组比较，去乙酰毛花甙组和依那普利拉组心肌力学指标均有不同程度提升，肝、肾、肠血流量增加（P〈0．05），血清cTnI、TBA、β2-MG浓度和DAO活性降低（P〈0．05）。去乙酰毛花甙＋依那普利拉组大鼠心肌力学指标全部升高，血流量分别为肝（240±49）PU、肾（239±75）Pu、肠（194±55）Pu，明显升高（P〈0．05），血清cTnI为（3．4±0．2）μg／L、TBA（47±8）μmol／L、B2-MG（2．01±0．16）mg／L、DAO（1．17±0．15）kU／L，均明显降低（P〈0．05）。结论严重烫伤后早期单用去乙酰毛花甙或依那普利拉，均能改善大鼠心功能，对肝、肾、肠损害有一定防治作用，两药配伍应用可产生协同作用。

Objective To investigate the effects of single or combined administration of cedilanid and small-dose of enalaprilat on heart, liver, kidney and intestine damages at early stage of severe scald in rats. Methods Forty healthy male Wistar rats were enrolled in the study and randomly divided into： sham, burn control, cedilanid, enalaprilat, cedilanid ＋ enalaprilat groups, with 8 rats in each group. Rats, except that of sham group （simulated scald with 37℃ water） were inflicted with 30% TBSA full-thickness scald, and were injected with Ringer＇s lactate solution （4 mL·kg^-1·1% TBSA^-1） intraperitonealy 30 minutes after burn. Then rats in cedilanid group were given cedilanid injection （0.2 mg/kg） intravenously, and those in enalaprilat group were given enalaprilat （1 mg/kg） , and cedilanid ＋ enalaprilat group with cedilanid and enalapril in the same dosage. At 6 post burn hour （PBH） or sham injury, parameters of myocardiac mechanics were recorded with the Multiple Channel Physiological Signal Collecting and Processing System. The blood flow of the liver, kidney and intestine was respectively detected with the Laser Doppler Flowmetry at 6 PBH. Serum contents of cTnl, TBA, beta2-MG and DAO were determined at 6 PBH to reflect visceral dam- ages. Results Compared with those in sham group, the parameters of myocardiac mechanics and blood flow of liver, kidney, intestine（ 158±32, 156±46, 119±30 PU, respectively）in burn control group were obviously decreased（ P〈0.05 ） , and the serum contents of eTnI, TBA, beta2-MG, DAO （5.0±0.3 μg/L, 82±23 μmol/L, 2.55± 0.15 mg/L, 1.52±0.08 kU/L, respectively） in burn control group were obviously increased （ P 〈 0.05 ）. Compared with those in burn control group, the parameters of myocardiac mechanics and blood flow of liver, kidney, intestine in the cedilanid or enalaprilat groups increased markedly, and their serum contents of cTnI, TBA, beta2-MG, DAO decreased significantly （ P 〈 0.05 ）. Compared with those in burn control group,the parameters of myoeardiae mechanics and blood flow of liver, kidney, intestine （240±49, 239±75, 194 ±55 PU, respectively） in cedilanid ＋ enalaprilat group increased significantly（ P 〈0.05） , and the serum contents of cTnI, TBA, beta2-MG, DAO （3.43 ±0.21μg/L, 47 ± 8 μg/L, 2.01 ± 0.16 mg/L, 1.17±0. 15 kU/L, respectively） were decreased （P〈0.05）. Conclu- sion Single administration of cedilanid or small-dose enalaprilat can ameliorate impairment of cardiac functions, prevent damages to liver, kidney and intestine in early stage of severe scald in rats. Combined administration of cedilanid and small-dose enalaprilat seems to be more effective.