改进的90%无血肝切除术与药物诱导建立大鼠急性肝衰竭模型  

Establishment of a rat model of acute liver failure by a modified 90% bloodless hepatectomy and by D-galactosamine and lipopolysaccharide injection

作　　者：宫绪萌[1] 周彬[2] 陈华木 杨方圆[2] 黄月朝 钟己生 高毅[1] 

机构地区：[1]南方医科大学珠江医院肝胆二科,广东广州510282 [2]南方医科大学第二临床医学院,广东广州510282

出　　处：《南方医科大学学报》2014年第8期1135-1139,共5页Journal of Southern Medical University

基　　金：国家863计划(2012AA020505);广东省中国科学院全面战略合作项目(2011B090300015);国家级大学生创新创业训练计划项目(201212121016);南方医科大学交叉学科创新团队培育计划项目"肝衰竭替代治疗相关肝组织工程生物材料和关键技术研发"~~

摘　　要：目的建立理想的大鼠急性肝衰竭(ALF)模型。方法 SD大鼠68只随机分为3组:(1)传统手术组,按Higgins和Anderson法直接套扎肝蒂切除90%大鼠肝脏;(2)改进手术组,采用改进无血肝切除术切除90%肝脏组织;(3)药物组,腹腔注射D-氨基半乳糖(700 mg/kg)+脂多糖(5μg/kg)。观察手术相关情况及建模后7 d大鼠存活率;检测肝功能指标包括谷丙转氨酶(ALT)、总胆红素(Tbil)、白蛋白(ALB)、血氨(NH3)、血糖(Glu)和凝血酶原时间(PT);观察建模后24、72 h肝脏组织病理变化。结果传统手术组术后出血死亡率高于改进手术组(15%vs 0);传统手术组、改进手术组、药物组大鼠建模后7 d存活率分别为0、25%和15%;改进手术组及药物组处理后24、72 h,ALT、Tbi、ALB、NH3、Glu、PT等均出现明显变化(P<0.05),其中ALT、Tbi、NH3、Glu、PT在改进手术组中均在24 h变化最明显,在药物组中均在72 h变化最明显,两组ALB则均在7 d下降至最低值后逐渐恢复;改进手术组残肝及药物组肝脏在24、72 h均出现不同程度的肝细胞变性坏死等表现。结论改进90%无血肝切除术及腹腔注射D-氨基半乳糖+脂多糖均可建立理想的大鼠ALF模型,可适用于不同的ALF相关研究。Objective To compare the effects of different approaches to establishing rat models of acute liver failure （ALF）. Methods Sixty-eight Sprague-Dawley rats were randomly divided into 3 groups for establishing ALF models using 3 different approaches, namely conventional hepatectomy for resecting 90% liver tissue as described by Higgins and Anderson, modified bloodless hepatectomy for resecting 90% liver tissue, and intraperitoneal injections of 700 mg/kg D-galactosamine （D-gal） and 5 μg/kg lipopolysaccharide （LPS）. The mortality of the rats due to postoperative bleeding and survival rate at 7 days after the surgery were recorded. The levels of alanine aminotransferase （ALT）, total bilimbin （Tbil）, albumin （ALB）, NHz, glucose （Glu） and prothrombin time （PT） were monitored, and histopathologies of the liver were examined at 24 and 72 h after the surgery. Results The mortality rate due to postoperative bleeding was higher in conventional hepatectomy group than in the modified surgical group （15% vs 0）. The survival rate at 7 days was 25%, 0%, 15% in conventional surgical group, modified surgical group and drug injection group, respectively. In the latter two groups, significant changes of ALT, Tbil, ALB, NH3, Glu, and PT were recorded at 24 and 72 h after the modeling （P〈0.05）, and these changes were the most obvious at 24 h in modified surgical group and at 72 h in the drug injection group; ALB in both groups declined to the lowest at 7 days and then increased gradually. Liver cell degeneration and necrosis were found in modified surgical group and drug injection group at 24 h and 72 h after the modeling. Conclusion Both the modified 90% bloodless hepatectomy and injections of D-gal and LPS can be used to establish ideal rat models of ALF to suit different ALF-related researches.

关 键 词：急性肝衰竭 肝切除术 D-氨基半乳糖 脂多糖 动物模型 

分 类 号：R657.3[医药卫生—外科学] R-332[医药卫生—临床医学]