依那普利拉对严重烧伤大鼠心肌损伤的保护作用及其机制探讨

Protective effects and mechanism of enalaprilat on myocardial injury of severely burned rats

目的探讨应用依那普利拉的早期干预对严重烧伤大鼠心肌损害的保护作用,并对其作用机制进行初步研究。方法 66只雌性清洁级SD大鼠,随机将大鼠分为对照组6只、烧伤组30只、治疗组30只。烧伤组和治疗组分为伤后1、3、6、12、24 h 5个时相点,每时相点6只大鼠。烧伤组与治疗组大鼠采用热水直接烫伤法制作严重烧伤模型,伤后予以腹腔注射补液抗休克,治疗组加用依那普利拉早期干预,均在伤后各时相点行腹主动脉采血,留取心脏组织,ELISA法检测血清心肌肌钙蛋白Ⅰ(cTnⅠ)、白介素1(IL-1)、肿瘤坏死因子α(TNF-α)、血管紧张素Ⅱ(AngⅡ)水平、心肌AngⅡ水平,部分心肌组织应用TUNEL法检测细胞凋亡情况。结果烧伤组与治疗组血清cTnI水平在伤后各时相点较对照组均有显著性升高(P<0.05),治疗组各时相点血清cTnI水平升高幅度均低于烧伤组(P<0.05);烧伤组与治疗组血清IL-1、TNF-α水平各时相点较对照组均有显著性升高(P<0.05),治疗组各时相点血清IL-1、TNF-α水平升高幅度均低于烧伤组(P<0.05);烧伤组心肌匀浆及血清中AngⅡ在伤后显著性升高(P<0.05),治疗组各时相点血清及心肌匀浆中AngⅡ水平升高幅度均低于烧伤组,其中伤后1、12 h差异有统计学意义(P<0.05);烧伤后心肌细胞凋亡数量在各个时相点显著增加,治疗组各个时相点凋亡数量显著少于烧伤组(P<0.05)。结论严重烧伤大鼠早期即发生心肌损伤,依那普利拉对烧伤大鼠心肌损伤起保护作用,其保护作用机制可能与减少烧伤后IL-1、TNF-α、AngⅡ的释放,减少心肌细胞凋亡有关。

Objective To observe the early situation of myocardial damage in rats,and explore the protective effect of enalaprilat＇s early intervention in myocardial damage in severely burned rats and to preliminarily study its mechanism of action,by the direct method of burns caused by hot water to build the rat model. Methods 66 female SD rats were randomly divided into the control group（ n = 6）,burn group（ n = 30）,and the treatment group（ n =30）. Burn and treatment groups were divided into 1,3,6,12,24 h time points after injury,each time point had six rats. The burn and the treatment group rats were taken use of the direct method of burns caused by hot water to build the severely burned model. The rats were given fluid infusion（ ip.） to anti-shock after injury. The treatment group was intervened with enalaprilat. The abdominal aortic blood and heart tissue were taken at each time point.The concentrations of serum cTnⅠ,IL-1,TNF-α,Ang Ⅱ and myocardial Ang Ⅱ were detected by ELISA. The myocardial apoptosis was detected by TUNEL. Results The concentrations of serum cTnⅠ of burn and treatment groups were significantly increased compared with the control group at each time point（ P 〈0. 05）. The increased rates of serum cTnⅠ concentrations of the treatment group were lower than the burn group（ P〈 0. 05）. The concentrations of serum IL-1 and TNF-α of burn and treatment groups were significantly increased compared with the control group at each time point（ P〈 0. 05）. The increased rates of serum IL-1 and TNF-α concentrations of treatment group were lower than the burn group（ P 〈0. 05）. The concentrations of myocardial homogenates and serum AngⅡ were significantly increased（ P〈 0. 05）. The increased rates of myocardial homogenates and serum AngⅡ of treatment group were lower than the burn group at each time point（ P 〈0. 05）. The number of myocardial apoptosis increased significantly after injury and the number of the treatment group was significantly less than burn group at each time point（ P〈 0. 05）. Conclusion Early myocardial damage occurs in severely burned rats. Enalaprilat takes protective effect in myocardial damage of severely burned rats. Enalaprilat can reduce the release of IL-1,TNF-α,AngⅡ and reduce myocardia apoptosis,then protect the heart.