肝糖原贮备的变化对热缺血再灌注期大鼠肝储备功能的影响

Effects of liver glycogen storage on hepatic functional reserve during warm ischemia and reperfusion injury in rats

目的探讨增加肝糖原贮备对肝缺血再灌注损伤的保护作用。方法建立大鼠肝热缺血再灌注模型。动物分组:(1)H组,于缺血前24h尾静脉注射25%葡萄糖(2mL/只,1次/6h);(2)L组,缺血前禁食24h,饮水不限;(3)缺血再灌注对照组(C组),建模前不注射葡萄糖,亦不禁食;(4)假手术对照组(N组)。H,L,C组动物于缺血45min,再灌注1/4h,1/2h和1h后取样测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(AKP)和吲哚氰绿代谢试验(ICGR15)、胰高血糖素负荷试验(GLT),同时取肝组织行光镜形态学观察。结果(1)肝储备功能(HFR):ICGR15在各个时点4组间差异有显著性,N组<H组<C组<L组(P<0.05或P<0.01);GLT,负荷后c-AMP浓度及应答比(CAR)在各个时点4组间差异有显著性,N组>H组>C组>L组(P<0.01)。H,C,L组的ICGR15和GLT在组内各时点间差异有显著性(P<0.05或P<0.01)。(2)肝酶学指标各时点4组间差异有显著性(P<0.05或P<0.01),N组<H组<C组<L组;各组内1/2h与1/4h之间差异无显著性(P>0.05)。(3)肝脏病理组织学改变:H组明显轻于C组及L组,并接近N组,L组最严重。结论(1)预防性增加肝糖原贮备能拮抗热缺血再灌注损伤过程中肝储备功能的损害。(2)ICGR15,GLT较常规肝功能酶学指标能更早期、灵敏反映肝热缺血再灌注过程中肝储备功能的变化。

ObjectiveTo study the role of hepatic glycogen reserve in pretecting the ischemia-reperfusion (injury) of rat liver. MethodsA model of rat liver warm ischemia and reperfusion injury (WIRI) was set up. Rats were divided into 4 groups:(1)Group H, given 25% glucose by tail vein injection(2ml,q6h,iv);(2)group L, food was not supplied (drinking unlimited) 24 hours before warm ischemia; (3)control group (group C), rats took food freely; and (4)sham operation group (group N). After 45 min of ischemia, reperfusion for 1/4h,1/2h and 1h, blood was taken to test for ICGR_(15)and GLT(glucagon loading test). Meanwhile, the levels of enzymes (including AST, ALT, AKP) were observed. Results(1) Hepatic functional reserve (HFP): ICGR15: groupN<groupH<groupC<groupL(P<0.05 or P<0.01). GLT: c-AMP level in plasma after GLT and c-AMP answering rate (CAR): group N>groupH>group C>groupL(P<0.01).There were significant differences of ICGR_(15), GLT between the periods of reperfusion of 1/2h,1/4h and 1h in group H, C and L (P<0.05 or P<0.01). (2) Enzyme level: There were signlficant differences in the same periods among the four groups (P<0.05 or P<0.01), groupN<groupH<groupC<group L. No difference was observed between 1/2h and 1/4h enzyme level in the groups(P>0.05). (3)Histopathologic changes in the liver:They were significantly milder in group H than in groups C and L, and the changes in group H were similar to group N. The changes in group L were the most severe. Conclusions(1)Prophylactic increase of hepatic glycogen storage could counteract the injury of hepatic functional reserve that occurs during warm ischemia and reperfusion. (2)The changes of hepatic functional reserve that occurs during warm ischemia reperfusion can be earlier and more sensitively reflected by ICGR_(15) and GLT than by the (routine) enzyme parameters of hepatic function.