PNU282987对烧伤休克犬复苏时脂质过氧化损伤和组织含水率的影响

目的：研究α7烟碱型乙酰胆碱受体（α7nAChR）激动剂PNU282987对致死性烧伤休克犬脂质过氧化损伤和组织含水率的影响.方法：成年雄性Beagle犬12只,按完全随机数字表法分为烧伤补液组和烧伤PNU282987组,每组6只.采用凝固汽油燃烧法造成50%总体表面积Ⅲ度烧伤.于伤后0.5 h分别通过颈静脉补液,烧伤补液组给予林格液,烧伤PNU282987组给予等量含有PNU282987 （0.38 mg/kg）的林格液.补液量和速率均根据Parkland公式确定.于伤前和伤后2、4、8、12和24 h颈静脉取血,测定丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性,并于伤后24 h处死动物,留取心、肝、脾、肺、肾和回肠组织,测定组织含水率.结果：两组犬伤后SOD水平显著降低;伤后4 h起烧伤PNU282987组SOD水平显著高于烧伤补液组（P＜0.05）,而单纯烧伤组SOD水平持续降低.两组犬伤后MDA水平均上升,伤后4h起烧伤PNU282987组血浆MDA水平均显著低于烧伤补液组（P＜0.05）.烧伤PNU282987组脏器含水率显著低于烧伤补液组心：（68.6±1.1）% vs.（78.3±1.8）%;肝：（70.0±1.4）% vs.（ 79.8±0.7）%;脾：（67.2±1.2）% vs.（78.8±0.8）%;肺：（74.3±0.5）% vs.（ 80.2±1.6）%;肾：（71.2±0.8）% vs.（ 80.1±0.9）%;回肠：（68.9±1.1）% vs.（ 78.7±0.8）%],差异均有统计学意义（P＜0.05）.结论：PNU282987能抑制烧伤休克犬复苏时引起的脏器氧自由基生成,减轻组织水肿,具有潜在临床应用价值.

Effect of PNU282987 on lipid peroxidative injury and tissue water content in dogs with lethal burn shock

Objective： To investigate the effect of PNU282987, a cholinergic agonist, on lipid peroxidative injury and tissue water content in dogs with lethal burn shock. Methods： Twelve adult male Beagle dogs were subjected to 50% total body surface area （TBSA） full-thickness flame injury, and then they were randomly divided into two groups, resuscitation group and PNU282987 group, with 6 animals in each group. The dogs in resuscitation group received Ringer＇s solution, and PNU282987 group received equal amount of Ringer＇s solution containing PNU282987 （0.38 mg/kg, diluted in Ringer＇s solution） 0.5 hour after injury. The delivery rate and volume of Ringer＇s solution was in accordance with that of Parkland formula（4 ml· kg^-1.1%TBSA 1）： in the first 8 hours half of the total volume was transfused uniformly, in the later 16 hours the other half of the total volume was transfused uniformly. The plasma levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were continuously determined before and 2, 4, 8, 12 and 24 hours after burn. The dogs were sacrificed at 24 hours after burn, and heart, liver, spleen, lung, kidney and intestine were harvested for assessment of tissue water con2 tent （ratio of dry to wet weight）. Results： The SOD activity was significantly decreased after burn compared to that before injury in both groups. The activity of SOD in PNU282987 group was significantly higher than that of the resuscitation group from 4 hours on after burn （P〈 0.05）, while the level of SOD in resuscitation group decreased progressively. The plasma levels of MDA increased in both two groups after burn, the level of MDA in PNU282987 group was significantly lower than that of the resuscitation group from 4 hours on after burn（P〈0.05）.The tissue water contents were significantly lower in PNU282987 group than resuscitation group in heart（68. 6± 1.1）% vs. （78. 3±1.8）%1, liverE（70.0±1.4）% vs. （79.8±-0.7）%, spleenr（67. 2±1. 2）% vs. （78. 8±0. 8）%, lung （74. 3±0. 5）% vs. （ 80. 24±1. 6）%1, kidney-（71.2±0.8）% vs. （ 80. 1±0.9）% and ileum （68.9±1.1）% vs. （78.7±0.8） %1 respectively, all P〈0.05. Conclusions： The results indicate that PNU282987 can alleviate visceral tissue edema and lower the lipid peroxidative injury in dogs with lethal burn injury.