1,6-二磷酸果糖对大鼠肝脏创伤救治的影响及其作用机制

Effect and mechanism of fructose-1,6-diphosphate on liver trauma treatment in rats

目的观察1,6-二磷酸果糖(FDP)在大鼠肝脏创伤救治中的作用并探讨其可能的机制。方法选取健康SD大鼠49只,建立肝脏撞击破裂伤模型。先取42只建模后大鼠,随机分为对照组、葡萄糖组、FDP组(n=14),分别于致伤10min后静脉注射0.9%氯化钠、5%葡萄糖及15%FDP注射液2ml(均在10min内静注完),各组再按处死取材时相点随机均分为缺血前和再灌注4h两个亚组(n=7)。剩余7只建模后大鼠为再灌注4h假手术组。测定各组动物外周血谷草转氨酶(AST)、谷丙转氨酶(ALT)水平,肝组织丙二醛(MDA)、糖原含量及超氧化物歧化酶(SOD)活性。结果在缺血前时相点,肝糖原含量对照组<葡萄糖组<FDP组(P<0.05),余各指标各组间比较无显著差异。与缺血前比较,再灌注4h时相点各组肝糖原含量均明显降低,除假手术组外,各组外周血ALT、AST水平及肝组织MDA含量均明显增高,肝组织SOD活性均明显降低(P<0.01)。再灌注4h时相点,外周血ALT水平对照组>葡萄糖组>FDP组>假手术组(P<0.01或P<0.05),AST水平对照组>葡萄糖组/FDP组>假手术组(P<0.01或P<0.05),FDP组与葡萄糖组比较无显著差异;肝组织SOD活性对照组<葡萄糖组<FDP组<假手术组(P<0.01或P<0.05),MDA含量对照组>葡萄糖组>FDP组>假手术组(P<0.01或P<0.05)。结论与葡萄糖比较,FDP对大鼠肝脏撞击破裂伤有更好的保护作用,其机制可能为在应激条件下肝脏能更有效地以FDP为底物合成糖原,增加肝脏缺血前糖原贮备,从而减轻肝脏创伤救治中的热缺血再灌注损伤。

Objective To investigate the effect and the possible mechanism of fructose-1,6-diphosphate （FDP） on liver trauma treatment in rats. Methods The liver rupture model was established with 49 healthy Sprague-Dawley rats by abdominal impact, and then 42 model animals were chosen and randomly divided into control group, glucose group and FDP group （14 each）, which were injected 2ml of 0. 9% sodium chloride, of 5% glucose and of 15% FDP, respectively, at 10 minutes after injury. Animals in each group were randomly divided into preischemia group and 4h reperfusion group （7 each） according to the sacrificed time point （before or after ischemia）. The 7 remains of model rats, as sham operation group （SH group）, were sacrificed at 4h reperfusion time point. The aspartate aminotransferase （AST） and alanine aminotransferase （ALT） levels of peripheral blood, the contents of glycogen and malondialdehyde （MDA）, and the activity of superoxide dismutase （SOD） were determined. Resulls At pre-ischemia time point, the contents of liver glycogen ranked as control group 〈 glucose group 〈 FDP group （P〈0. 05）, and no significant difference was found in other markers among the 3 groups. As compared with pre-ischemia time point, glycogen contents decreased significantly in 4h reperfusion time point （P〈0. 01）, while ALT and AST levels of peripheral blood and MDA contents of liver tissue increased and SOD activity decreased significantly （P〈0. 01） except in SH group. At 4h reperfusion time point, the ALT levels in peripheral blood of 4 groups ranked as control group 〉 glucose group 〉 FDP group 〉 SH group （ P〈0. 01 or P〈0. 05）, while the AST levels ranked as control group 〉 glucose group/ FDP group 〉 SH group （ P 〈0. 01 or P〈0. 05）, and no significant difference existed between glucose group and FDP group; the SOD activity of liver tissue ranked as control group 〈 glucose group 〈 FDP group 〈 SH group （P〈0. 01 or P〈0. 05）, and the MDA contents ranked as control group glucose group 〉 FDP group 〉 SH group （P〈0. 01 or P〈0. 05）. Conelusions As compared with glucose, the application of FDP has a better protective effect on impact iniury of liver rupture in rats. The mechanism might be that FDP is a re,ore effective substrate for glycogen synthesis in liver under stress conditions, and can increase the reserve of liver glycogen before ischemia, thus abate the ischemiareperfusion injuries in therapeutic treatments of traumatic liver.