急性肝功能衰竭猪应用同种体外肝脏灌注技术支持的实验研究

目的 评价体外肝脏灌注（extracorporeal liver perfusion,ECLP）技术应用于急性肝功能衰竭（acute liver failure,ALF）短暂替代治疗的疗效和可行性。方法 实验动物均为健康普通长白猪,体重20～30kg。按随机数字表法随机分为3组：肝衰组（n=5）,通过结扎肝脏血供和门体分流制备肝衰模型,肝衰模型制成8h后处死取标本;肝衰＋ECLP组（n=5）,受体为肝衰猪,供肝阻断血供后迅速切取,连接ECLP开始灌注,ECLP灌注时间为4h,肝衰模型制成8h后处死取标本;正常肝＋ECLP组（n=4）,受体为正常猪,灌注方法同肝衰＋ECLP组。观察受体一般情况、肝脏和脑组织病理变化,检测受体血常规、血生化、血凝、血氨和TNF等指标。结果 肝衰组PT、AST、TNF、血氨、RBC和HCT值明显高于肝衰＋ECLP组（P〈0．05）;正常肝＋ECLP组的FIB、AST、TNF和血氨的变化明显低于肝衰＋ECLP组（P〈0．05）。病理学检查显示,肝衰组受体的脑组织出现广泛的脑水肿,表现为神经元细胞问隙明显增宽,并有多数神经元细胞死亡;肝衰＋ECLP组受体的脑组织也出现有脑水肿的表现,并有少数神经元细胞死亡,但较肝衰组轻;正常肝＋ECLP组的脑组织病理检查基本正常。肝衰组和肝衰＋ECLP组的受体肝脏病理检查可见大片肝细胞坏死,而正常肝＋ECLP组受体的肝脏病理检查基本正常。结论 同种ECLP能有效地改善肝衰受体的体内环境,缓解症状．尤其是这种技术能缓解肝衰受体的脑水肿,而脑水肿可能是肝衰受体最主要的致死原因,但ECLP也有其自身的并发症存在。总之,同种ECLP技术是一种有效而且可行的ALF短暂替代治疗方案。

Effect of Extracorporeal Liver Alloperfusion in Treatment of Acute Liver Failure in Pigs

Objective To evaluate the feasibility and curative effect of extracorporeal liver perfusion (ECLP) in treatment of acute liver failure (ALF) in pigs. Methods The experiments were carried out in healthy pigs (weight 20-30 kg) under general anesthesia. All of the pigs were randomly divided into 3 groups. ALF model was established by liver blood supply obstructing and portal-systemic shunting. ALF group (n=5): ALF pigs were killed 8 h after establishing. ALF+ECLP group (n=5): ALF pigs were perfused with ECLP for 4 h and killed 8 h after establishing. Normal liver+ECLP group (n=4): normal pigs were dealt with just as ALF+ECLP group. The data of PT, AST, TNF, blood ammonia were collected in all groups. Pathologic changes in liver and brain were detected. Results The levels of PT, AST, TNF, blood ammonia, RBC and HCT in the ALF+ECLP group were lower than those in the ALF group (P<0.05). In the normal liver+ECLP group, the levels of FIB, AST, TNF and blood ammonia were lower than those in the ALF+ECLP group (P<0.05). The pathologic examination showed that extensive hydrocephalus in the ALF group which was more serious than that in the ALF+ECLP group. Hydrocephalus could not be found in the normal liver+ECLP group. Massive hepatocyte necrosis was observed in the livers of ALF group and ALF+ECLP group but was not found in the normal liver+ECLP group. Conclusion The results suggest that ECLP can effectively improve the internal environment in ALF pigs and alleviate hydrocephalus which is the main cause of death in ALF. But ECLP has its complications. In a word, ECLP is an effective and feasible "bridge" treatment of ALF in pigs.