缺血预处理对老年大鼠肝硬化肝脏保护作用及其机制探讨  

Effect of ischemic preconditioning on the ischemia-reperfusion injury of the aged rat liver with cirrhosis.

作　　者：程向东[1] 江献川[2] 彭承宏[2] 刘颖斌[2] 徐斌[2] 彭淑牖[2] 

机构地区：[1]浙江省肿瘤医院肝胆外科,杭州市310022 [2]浙江大学医学院附属第二医院普外科

出　　处：《中华老年医学杂志》2002年第6期430-432,共3页Chinese Journal of Geriatrics

基　　金：浙江省卫生厅科研基金资助项目 (M 9810 )

摘　　要：目的　探讨缺血预处理对老年大鼠肝硬化肝脏缺血再灌注损伤的保护作用和机制。　方法　老年肝硬化SD雄性大鼠 40只 ,随机分为 5组 ,每组 8只。以肝组织ATP、ADP、AMP、能荷及血清丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、乳酸脱氢酶 (LDH)和肝脏胆汁分泌量来评价肝功能 ,检测肝组织P 选择素蛋白表达并计算肝组织中性粒细胞浸润数。　结果　缺血再灌注 12 0min后 ,缺血预处理 (IPC)组和精氨酸预处理 (APC)组ATP含量和能荷水平明显高于缺血再灌注 (I/R)组〔分别为 (4 1± 1 6)、(4 0± 1 6)、(1 5± 0 6)U/L和 (0 6± 0 1)、(0 6± 0 1)、(0 4± 0 1)U/L ,均为P<0 0 1〕 ,而Nω 硝基 L 精氨酸甲酯预处理 (NPC)组与I/R组间差异无显著性 (P >0 0 5 )。IPC组和APC组ALT、AST、LDH受到明显抑制 (P <0 0 1)。肝组织胆汁分泌量 ,IPC组明显多于I/R组〔(0 10±0 0 3 )和 (0 0 7± 0 0 3 )ml/g肝组织 ,P <0 0 1〕 ,APC组与I/R组差异有显著性 (P <0 0 1)。IPC组和APC组中白细胞浸润受到抑制。I/R组肝细胞P 选择素蛋白表达显著增强 (P <0 0 1) ,IPC组和APC组明显抑制 ,而NPC组增强 (P <0 0 1)。肝组织中P 选择素蛋白表达与中性粒细胞浸润数之间呈显著正相关 (r=0 60 ,P <0 0 1)。?Objective To investigative the effects and mechanisms of ischemic preconditioning(IPC) on the ischemia-reperfusion(I/R) injury of liver of cirrhosis aged rat. Methods Forty male aged SD rats with liver cirrhosis were allowed to 5 groups randomly, eight rats in each group.Hepatocellular viability was assessed by hepatic adenine nucleotide level,energy charge,ALT, AST,LDH in serum and bile output .The expression of P-selectin in the liver tissue was located and analyzed by immunohistochemitry technique.Leukocyte count in ischemic hepatic lobe was calculated. Results At 120 min after reperfusion,the level of ATP and EC in Ischemic precontioning group(IPC group),L-Argine preconditioning group(APC group) were higher than those in Ischemia/reperfusion group(I/R group) significantly〔(4.1±1.6 )and (4.0±1.6 )U/L versus (1.5±0.6) U/L,(0.6±0.1) versus (0.4±0.1)U/L respectively,P<0.01〕. The increases in AST,ALT and LDH were prevented in IPC and APC groups.The livers produced more bile in IPC group than in I/R group during 120 min after reperfusion〔(0.10±0.03) versus (0.07±0.03) ml/g liver, P<0.01〕.There was significant difference between APC and I/R group (P<0.01). The increase in the leukocytes count was prevented in IPC and APC group. Significant promotion of the expression of P-selectin in hepatocytes in the I/R group was observed with respected to the SO group (P<0.01). IPC or L-argine attenuated P-selectin expression significantly(P< 0.01). The degree of P-selectin expression was positive correlation with the counts of leukocyte infiltrating in liver(r=0.60,P<0.01). Conclusions IPC abolishes ischemic reperfusion injury induced leukocyte adhesion and infiltration by preventing postischemic P-selectin expression in the aged rat liver with cirrhosis via a NO-initiated pathway.

关 键 词：老年大鼠 缺血预处理 肝硬化 P选择素 一氧化氮 作用机制 

分 类 号：R363[医药卫生—病理学]