肝外门静脉梗阻对抗凝血因子水平的影响

摘要

目的 探讨肝外门静脉梗阻对血清抗凝血因子水平的影响.方法 2016年3月至2016年12月,将25只成年新西兰雄性白兔(体重:2.2～3.4 kg,平均2.9kg)采用部分结扎肝外门静脉主干的方法制作成肝外门静脉高压兔模型.10只成年新西兰雄性白兔作为正常对照组.所有动物手术前后测量门静脉压力和脾脏大小,于术后4周再次手术测量门静脉压力和脾脏大小,并收集静脉血.采用蛋白C、蛋白S和抗凝血酶Ⅲ试剂盒,利用ELISA技术检测蛋白C、蛋白S和抗凝血酶Ⅲ的血清浓度.比较肝外门静脉高压模型与对照组的蛋白C、蛋白S和抗凝血酶Ⅲ水平的差异.结果 25只采用部分结扎肝外门静脉主干方法制作的肝外门静脉梗阻兔模型,其中8只因伤口感染裂开、门静脉高压出血死亡,其余17只均成功制作肝外门静脉高压模型,术后4周肝外门静脉压力显著高于术前[(25.1±7.2) cmH2O比(10.6±2.6)cmH2O,P＜0.01];术后4周脾脏大小明显大于术前[长径:(6.0±0.8) cm比(5.3±0.5) cm,P=0.045;宽径:(1.2±0.3)cm比(1.0±0.2)cm,P=0.002].肝外门静脉梗阻组的蛋白C和抗凝血酶Ⅲ浓度显著低于对照组[PC:(21.1±2.7)μg/ml比(32.7±4.0)μg/ml,P=0.015;ATⅢ:(25.5±5.5)μg/ml比(38.6±4.3)μ上g/ml,P=0.031],两组蛋白S浓度无差别[(7.4±1.4)μg/ml比(6.6±1.7) μg/ml,P=0.584].结论 肝外门静脉梗阻导致蛋白C和抗凝血酶Ⅲ显著降低,是人肝血流减少导致的.%Objective To explore the effect of extrahepatic portal venous obstruction upon the levels of protein C,protein S and antithrombin Ⅲ in rabbits.Methods From March 2016 to December 2016,25 New Zealand white rabbits were used for modeling of extrahepatic portal hypertension by partial ligation of extrahepatic portal vein.The mean weight was 2.9 (2.2-3.4) kg.And another 10 rabbits were used as control group.The portal pressure and size of spleen were measured pre-and post-operatively at 4 weeks.The blood samples were collected at 4 weeks for detecting the serum levels of protein C,protein S and antithrombin Ⅲ by enzyme-linked immunosorbent assay (ELISA).And the levels of protein C,protein S and antithrombin Ⅲ were compared between two groups.Results Seventeen animal models of extrahepatic portal hypertension were established successfully and eight animals died from wound infection or bleeding due to portal hypertension.Portal pressure increased significantly from preoperative (10.6 ± 2.6) cmH2O to postoperative (25.1 ±7.2) cmH2 O (P＜0.01).The size of spleen increased significantly after 4 weeks [length:(6.0±0.8) vs.(5.3±0.5)cm,P =0.045;width:(1.2±0.3) vs.(1.0±0.2)cm,P =0.002].The levels of protein C and antithrombin Ⅲ in model group were significantly lower than those in control group [PC:(21.1±2.7) vs.(32.7 ± 4.0) μg/ml,P =0.015;AT Ⅲ:(25.5±5.5) vs.(38.6± 4.3) μg/ml,P =0.031].No significant inter-group difference existed in the level of protein S.Conclusions The deficiency of protein C and antithrombin Ⅲ is caused by reduced hepatopetal blood flow due to extrahepatic portal venous obstruction.