PNU282987对致死性烧伤休克犬器官功能和存活率的影响

Effects of PNU282987 on organ function and survival in dogs with lethal burn shock

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器官功能和存活率的影响。方法成年雄性Beagle犬12只，按完全随机数字表法分为单纯烧伤组和PNU282987组（PNU组），每组6只。采用凝固汽油燃烧法造成50％总体表面积Ⅲ度烧伤休克模型，PNU组于伤后静脉泵入PNU2829870．38mg／kg；单纯烧伤组给予等量生理盐水。于伤前和伤后0．5、2、4、8、12、24h，在非麻醉状态下测定平均动脉压（MAP）及血浆肿瘤坏死因子-α（TNF-α）、丙氨酸转氨酶（ALT）、肌酐（Cr）、尿素氮（BUN）、肌酸激酶同工酶（CK-MB）的变化，并记录伤后24h存活率。结果两组犬伤后MAP明显降低；伤后4h起PNU组MAP显著高于单纯烧伤组，于24h时恢复至伤前水平的83．6％；而单纯烧伤组MAP呈进行性降低，直至死亡。PNU组伤后各时间点血浆TNF-α水平均显著低于单纯烧伤组。单纯烧伤组伤后ALT（U/L）、Cr（moUL）、BUN（μmmol／L）和CK-MB（U/L）水平持续升高；而PNU组除ALT持续升高外，其余指标均呈先升高后下降趋势，且至12h时PNU组上述指标均显著低于单纯烧伤组（ALT：51．2±7．0比104．8±7．4，Cr：42．7±5．4比88．5±4．8，BUN：4．9±1．2比14．7±1．4，CK-MB：564．0±39．1比734．0±35．9，均P〈0．05）。PNU组伤后24h存活率为50％（3，6），显著高于单纯烧伤组0（0／6）。结论PNU282987能改善致死性烧伤休克犬24h存活率，降低炎症因子水平，保护器官功能，具有潜在临床应用价值。

Objective To investigate the effects of PNU282987, a α7 nicotinic acetylcholine receptor agonist （α7nAChR）, on organ function and survival rate 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 a burn group and a PNU282987 group （PNU group）, each n=6. The dogs in PNU group received PNU282987 （0.38 mg/kg, venous pumping） and the dogs in burn group received equal amount of normal saline solution as the control group. The mean arterial pressure （MAP） and the plasma levels of tumor necrosis factor-α （TNF-α ）, alanine aminotransferase （ALT）, MB isoenzyme of creatine kinase （CK-MB）, creatinine （Cr）, blood urea nitrogen （BUN） were continuously determined before and 0.5, 2, 4, 8, 12, 24 hours after burn. All the above measurements were performed with animals in conscious and cooperative state. At the end of 24-hours-period experiment, the survival rate was recorded. Results The MAP significantly decreased after burn compared with the baseline data before-injury. The level of MAP in PNU group were significantly higher than those of the burn group from 4 hours after burn, and it returned to 83.6% of baseline level at 24 hours. In contrast, those in the burn group progressively decreased with time till death. The plasma levels of TNF- α in PNU group were significantly lower than those of burn group at each time points post injury. The ALT （U/L）, Cr （μmol/L）, BUN （mmol/L） and CK-MB （U/L） of the burn group increased pesistently, while those of the PNU group increased at first and decreased subsequently except for ALT increased pesistently, and they were all significantly lower than those of the burn group till to the time point of 12 hours （ALT： 51.2 ±7.0 vs. 104.8 ±7.4, Cr：42.7 ±5.4 vs. 88.5 ±4.8, BUN：4.9 ± 1.2 vs. 14.7 ± 1.4, CK-MB：564.0 ±39.1 vs. 734.0 ± 35.9, all P〈0.05）. At the end of 24-hours-period experiment, the survival rate of the PNU group was 50% （3/6） and significantly higher than that of the burn group 0 （0/6）. Conclusions The results indicated that PNU282987 decrease the levels of inflammatory cytokine, improve the organ functions and increase 24-hour survival rate in dogs with lethal burn injury. And PNU282987 may have potential clinical application.