肝细胞移植联合肝再生增强因子治疗大鼠急性肝功能衰竭的研究  

Combining hepatocyte transplantation intraperitoneally and augmenter of liver regeneration for acute hepatic failure in rats

作　　者：王志毅[1] 张艳[1] 石小枫[1] 刘杞[2] 

机构地区：[1]重庆医科大学附属第二医院感染科,重庆400010 [2]重庆医科大学病毒性肝炎研究所

出　　处：《第三军医大学学报》2007年第10期899-902,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30170843);重庆市重点项目{渝科发计字[2001]38号}~~

摘　　要：目的探讨同种异体肝细胞腹腔移植联合肝再生增强因子(augmenter of liver regenration,ALR)对D-氨基半乳糖(D-gal)诱导的急性肝功能衰竭大鼠的治疗作用。方法采用D-gal诱导大鼠急性肝功能衰竭,诱导后24h,59只大鼠随机数字表法分成4组。Ⅰ组15只:腹腔注射生理盐水;Ⅱ组15只:经腹腔移植2×107肝细胞,以后腹腔注射生理盐水;Ⅲ组15只:经腹腔移植2×107肝细胞,同时腹腔注射ALR50μg.kg-1.d-1;Ⅳ组14只:腹腔注射ALR50μg.kg-1.d-1。观察大鼠的存活率、肝脏功能、移植肝细胞存活情况、病理变化。结果Ⅱ组、Ⅲ组大鼠存活率(46.7%、66.7%)显著高于Ⅰ组(0.0%)(P=0.006;P=0.0002),Ⅲ组(66.7%)与Ⅳ组(14.3%)有显著差异(P=0.008),其他组间无明显差异(P>0.05)。移植后第1、2天Ⅱ组腹水AST高于Ⅲ组(P=0.001),Ⅱ组第1、2天腹水ALT高于Ⅳ组,Ⅱ组、Ⅲ组第1、2天腹水TBil高于Ⅰ组(P<0.05)。Ⅲ组肝脏病理改变轻于其他组。Ⅲ组大鼠腹腔移植的肝细胞存活数多于Ⅱ组。结论同种异体肝细胞经腹腔移植联合ALR可明显改善D-gal诱导的肝衰竭大鼠的存活率,促进移植肝细胞存活和增殖,促进肝组织及功能恢复。Objective To investigate the effect of allogeneic hepatocyte transplantation （HcT） plus augmenter of liver regenration （ALR） intraperitoneally on acute hepatic failure （ AHF ） induced by D-galactosamine （D-gal） in rats. Methods AHF was induced by D-gal in SD rats. HcT was received 24 h after intoxication, and the AHF rats were divided into four groups randomly. Group Ⅰ received normal saline （NS） intraperitoneally. Group Ⅱreceived 2 ×10^7 hepatocytes intraperitoneally and daily NS. Group Ⅲ received 2 × 10^7 hepatocytes intraperitoneally and daily intraperitoneal injection of ALR （50 μg · kg ^- 1· d ^-1 ） simultaneously. Group Ⅳ received daily intraperitoneal injection of ALR （50 μg · kg ^- 1· d ^-1 ）. The survival rate of rats, the survival rate of transplanted hepatocytes, liver function and liver histology of all rats were observed. Results Survival rate of Group Ⅱ , Group Ⅲ was higher than that of Group Ⅰ（46.7%, 66.7% vs 0. 0%, P =0. 006, P =0. 000 2）, that of Group Ⅲ was higher than Group Ⅳ（66.7% vs 14.3%, P =0. 008）, without significant difference among other groups. Ascitic aspartate aminotransferase （AST） of Group Ⅱwas higher than that of Group Ⅲon day 1, 2 after transplantation （P =0. 001 ）. Ascitic alanine aminotransferase （ALT） of Group Ⅱwas higher than that of Group Ⅳon day 1, 2 after transplantation （ P 〈 0. 05 ）. Ascitic total bilirubin of Group Ⅱ , Group Ⅲwas higher than that of Group Ⅰ （P 〈 0. 05 ）. Hepatic histologic changes of Group Ⅲwas improved more than other groups. The function and histologic changes of transplanted hepatocytes were obviously improved in Group Ⅲas compared with that of Group Ⅱ. Conclusion After HcT plus ALR intraperitoneally, the survival rate of AHF rats intoxicated with D-gal was increased, and their liver function and histologic changes were also improved. ALR improved the survival and proliferation of transplanted hepatocytes.

关 键 词：肝细胞移植 肝再生增强因子 急性肝功能衰竭 

分 类 号：R575.305[医药卫生—消化系统] R657.3[医药卫生—内科学]