微囊化肝细胞移植治疗大鼠急性肝功能衰竭的研究  

Experimental study in the treatment of acute liver failure with intraperitoneal microencapsulated hepatocytes in rats

作　　者：章志宇[1] 陈卫昌[1] 赵钢[2] 陈琳[2] 

机构地区：[1]苏州大学医学院附属第一医院,215006 [2]大连医科大学附属第一医院

出　　处：《中国航天医药杂志》2003年第6期7-11,共5页Medical Journal of CASE

摘　　要：目的探讨应用生物微胶囊包裹肝细胞(microencapsulatedhepatocyte)腹腔移植治疗急性肝功能衰竭的机制与可行性,评价生物膜功能。方法D-氨基半乳糖(D-gal)诱发急性肝功能衰竭大鼠模型,造模动物随机分成5组:Ⅰ组生理盐水组;Ⅱ组空微胶囊对照组;Ⅲ组促肝细胞生长素(hepatocytegrowthfactor,HGF)组;Ⅳ组裸肝细胞组;Ⅴ组微囊化肝细胞组,观察造模动物的2周存活率及死亡时间、肝功生化指标的变化,2周后收集腹腔内微胶囊,观察其形态与功能。结果Ⅴ组动物的存活率较Ⅳ、Ⅲ、Ⅱ、Ⅰ组有明显提高(分别为66.7%、33.3%、20%、13.3%、20%,P<0.05),其它组间存活率无显著性差异;Ⅴ、Ⅳ、Ⅲ组动物的存活时间明显长于Ⅱ组与Ⅰ组(分别为86.0±7.0、84.0±6.0、83.0±6.0、72.0±5.0、65.0±4.0小时,P<0.05);Ⅴ组移植后24小时起白蛋白(ALB)、总胆红素(TBIL)、凝血酶原时间(PT)较其它组有明显提高(P<0.05)。2周后腹腔收集的空微胶囊形态完整,微囊内肝细胞部分保持存活,Ⅳ组腹腔中大部分游离肝细胞被大网膜包裹破坏。结论微囊化肝细胞移植可以明显提高肝功能衰竭大鼠的存活率,延长生存时间,显著改善肝生化功能。生物微胶囊可以有效阻断免疫排斥反应,保护移植肝细胞,有利于其发挥生物功能。Objective To evaluate the feasibility of this method by transplanting the microencapsulated hepatocytes intraperitoneally, as while to examine the function of the bio-membrane, and also to elucidate the mechanisms of the effects. Methods All the model rats of acute liver failure were induced by D-galactosamine and were divided into 5 groups at random 48 hours after drug induction:Ⅰ. NS group (n=15);Ⅱ. free capsule group (n=15);Ⅲ. HGF group(n=15);Ⅳ. free hepatocyte group;Ⅴ. microencapsulated hepatocyte group. Two weeks later,observed the survival rate, living time and changes of liver biochemical markers; collectd the microcapsules in the survival rats'bodys and observed the histological changes and microcapsules'function. Results The survival rate of group Ⅴwas higher than that of Ⅳ、Ⅲ、Ⅱ、Ⅰgroup(respectively 66.7%,33.3%,20%,13.3%,20%,P<0.05).The living time of Ⅴ,Ⅳ,Ⅲgroup was longer than that of Ⅱ, Ⅰgroup. ALB,TBIL,PT of groupⅤimproved markedly than other groups from the time 24 hours after transplantation. Two weeks later, the microcapsules collected from the survival rats remained smooth and intact, the hepatocytes inside remained alive partially, while the free hepatocytes in peritoneal of group Ⅳwere coated by the great omentum and were destroyed 24 hours after transplantation. Conclusion Microencapsulated hepatocyte transplantation can improve the survival rate of acute liver failure rats and spread the life time, also can improve the liver biochemical function as well. During the course of transplantation, the shape and structure of microcapsules remained stable perfectly, and has showed no impacts on the body, which can prevent the hepatocyte from destruction due to the immune responses and can also help them perform function better.

关 键 词：微囊化肝细胞移植 治疗 大鼠 急性肝功能衰竭 生物膜功能 ALF 

分 类 号：R657.3[医药卫生—外科学]