褪黑激素对严重烧伤大鼠心肌损害的保护作用

Protective effect of melatonin on myocardial injury in severelyburned rats

目的探讨褪黑激素（MLT）对严重烧伤大鼠早期心肌损害的保护作用及机制。方法将30只SD大鼠按随机数字表法分为假伤组、烧伤组和MLT组，每组10只。采用大鼠背部皮肤浸入沸水中15s造成30％总体表面积Ⅲ度烫伤复制烧伤动物模型；假伤组大鼠背部皮肤浸入37℃水中。伤后立即腹腔注射溶剂（1％乙醇生理盐水）或MLT10mg／kg。伤后6h鼠尾取血后处死大鼠，取心肌组织，检测丙二醛（MDA）和还原型谷胱甘肽（GSH）含量、谷胱甘肽过氧化物酶（GSH—Px）和髓过氧化物酶（MP0）活性，以及血清肌酸激酶（CK）和乳酸脱氢酶（LDH）水平。结果与假伤组比较，烧伤后心肌组织MDA含量升高了66．7％（nmol／mg：1．55±0．17比0．93±0．05），GSH含量下降了27．8％（nmol／mg：13．58±0．33比18．82±0．55，均P〈0．01），GSH—Px活性被轻度抑制（nmol·min·mg-1：74．04±3．42比93．79±3．76，P〈0．05），MP0活性则增加至2．8倍（U／g：9．43±1．15比3．41±0．27，P〈0．01），提示心肌产生明显的氧化应激损伤。除GSH—Px外，MLT治疗可改善上述各种异常，与烧伤组比较差异均有统计学意义[MDA（nmol／mg）：0．89±0．08比1．55±0．17，GSH（nmol／mg）：17．23±0．54比13．58±0．33，MP0（U／g）：6．91±0．51比9．43±1．15，P〈0．05或P〈0．01]。此外，烧伤后血清CK及LDH水平分别较假伤组增加至37．8倍和7-4倍（均P〈0．01）；MLT治疗后二者分别降低了32．9％及21．2％（P〈0．05和P〈0．01）。结论MLT对严重烧伤早期的心肌损害具有保护作用，其机制可能和MLT抑制烧伤诱导的氧化应激损伤有关。

Objective To investigate the protective effect of melatonin （MLT） on myocardial injury in severely-burned rats and its mechanism. Methods A total of 30 Sprague-Dawley （SD） rats were randomly assigned to three groups： sham group, bum group and MLT group, each n = 10. The dorsal skin of animal was immersed into boiling water for 15 seconds to induce 30% total body surface area （TBSA） full-thickness burn, or immersed into 37 ℃ water for sham operation. Immediately after burn, the animals in burn group and MLT group were given intraperitoneally vehicle （ 1% alcohol in normal saline） or MLT （ 10 mg/kg） respectively. Six hours postburn, the blood from tail vessel was collected for serum preparation. After sacrificed, the myocardial tissues of rats were collected for the determination of malondialdehyde （MDA） and reduced glutathione （GSH） as well as glutathione peroxidase （GSH-Px） and myeloperoxidase （MPO） activities. Serum levels of creatine kinase （CK） and lactate dehydrogenase （LDH） were also estimated. Results Compared with the sham control, burn injury increased MDA by 66.7% （nmol/mg： 1.55 ± 0.17 vs. 0.93 ±0.05） and decreased GSH by 27.8% （nmol/mg： 13.58 ±0.33 vs. 18.82 ±0.55, both P〈O.01） in myocardial tissues, GSH-Px activity was also slightly inhibited （nmol rain-1 rag74.04 ± 3.42 vs. 93.79 ± 3.76, P〈0.05 ）, but MPO level was found to increase to 2.8 folds （U/g： 9.43 ± 1.15 vs. 3.41 ± 0.27 ,P〈0.01 ）. These changes indicated the occurrence of oxidative stress in myocardial tissues after severe burn. MLT treatment relieved most of the abnormality with significant statistical significances MDA （nmol/mg） ： 0.89 ± 0.08 vs. 1.55 ± 0.17, GSH （nmol/mg） ： 17.23 ± 0.54 vs. 13.58 ± 0.33, MPO （U/g） ： 6.91 ± 0.51 vs. 9.43 ± 1.15, P〈0.05 or P〈0.01 ]. In addition, the serum levels of CK and LDH in bum group increased to 37.8 folds and 7.4 folds respectively （both P〈0.01 ）. MLT treatment reduced CK by 32.9% and reduced LDH by 21.2% （P〈0.05 and P〈0.01）. Condusion MLT treatment exerts the protective effect on myocardial injury in severely-burned rats, which is attributed predominantly to its inhibition on burn-induced oxidative stress injury.