CAJ | 학술논문

目的探讨骨髓间充质干细胞(MSC)移植对大鼠暴发性肝功能衰竭(FHF)的治疗作用.方法全骨髓细胞贴壁培养筛选法分离纯化大鼠MSC；四氯化碳灌胃制作大鼠FHF模型,分为实验组和模型对照组,各20只,8只灌服等剂量0.9％氯化钠溶液作为空白对照组.将4 ’,6-二脒基-2-苯基吲哚(DAPI)标记的大鼠MSC 1.0×106从尾静脉移植入实验组和空白对照组,等剂量0.9％氯化钠溶液尾静脉注入模型对照组；分别于术后7、14 d处死各组部分大鼠,评价实验组与模型对照组大鼠一般状况、生存率、肝功能、TNF-α水平、肝脏病理、MSC归巢至肝脏的情况.正态分布资料采用两个独立样本t检验,非正态分布资料采用非参数检验.结果术后3d开始,实验组存活大鼠一般情况比模型对照组好转更加明显；术后7d,实验组与模型对照组各有15只和8只大鼠存活,差异有统计学意义(x2 =4.122,P＜0.05)；术后7d以及14 d,实验组与模型对照组相比,肝功能指标、TNF-α水平均差异均有统计学意义(均P＜0.05),病理学检查肝组织炎性反应改善情况实验组均更为明显；术后实验组MSC归巢细胞逐渐增多,空白对照组只观察到很少量归巢细胞.结论 MSC经尾静脉同种异体移植,可以归巢到肝功能衰竭大鼠肝脏,改善大鼠免疫和肝脏组织炎性反应坏死状态,促进FHF大鼠肝功能的恢复,对FHF具有明显的治疗作用.
목적 탐토골수간충질간세포(MSC)이식대대서폭발성간공능쇠갈(FHF)적치료작용.방법 전골수세포첩벽배양사선법분리순화대서MSC；사록화탄관위제작대서FHF모형,분위실험조화모형대조조,각20지,8지관복등제량0.9％록화납용액작위공백대조조.장4 ’,6-이미기-2-분기신타(DAPI)표기적대서MSC 1.0×106종미정맥이식입실험조화공백대조조,등제량0.9％록화납용액미정맥주입모형대조조；분별우술후7、14 d처사각조부분대서,평개실험조여모형대조조대서일반상황、생존솔、간공능、TNF-α수평、간장병리、MSC귀소지간장적정황.정태분포자료채용량개독립양본t검험,비정태분포자료채용비삼수검험.결과 술후3d개시,실험조존활대서일반정황비모형대조조호전경가명현；술후7d,실험조여모형대조조각유15지화8지대서존활,차이유통계학의의(x2 =4.122,P＜0.05)；술후7d이급14 d,실험조여모형대조조상비,간공능지표、TNF-α수평균차이균유통계학의의(균P＜0.05),병이학검사간조직염성반응개선정황실험조균경위명현；술후실험조MSC귀소세포축점증다,공백대조조지관찰도흔소량귀소세포.결론 MSC경미정맥동충이체이식,가이귀소도간공능쇠갈대서간장,개선대서면역화간장조직염성반응배사상태,촉진FHF대서간공능적회복,대FHF구유명현적치료작용.
Objective To investigate the therapeutic effects of mesenchymal stem cells (MSC) on rat fulminant hepatic failure (FHF). Methods The rat MSC were separated and purified by adherent culture of whole bone marrow cells. The rat FHF models were established by CCl4 intragastric administration.The rats were divided into experimental group (n=20) and model control group (n=20).And the same dose of saline was administered to rats as normal controls (n=8).Dosage of 1.0 × 106 4',6-diamidino-2-phenylindole (DAPI) labeled MSC were transplanted into rats in experimental group and normal control group through caudal veins,and the same dose of saline was given intravenously in model control group.Part of rats in each group were sacrificed after 7 days and 14 days of injection to evaluate the general condition,survival rate,liver function,tumor necrosis factor (TNF)-α level,liver pathology and MSC homing to the liver between experimental group and model control group.Normal distribution data were compared by independent-sample t test and nonnormal distribution data were analyzed by non-parameter test.Results After 3 days of injection,the general condition of experimental group were better than the model control group. After 7 days of injection,there were 15 and 8 survival rats,the survival rates were statistically different between experimental group and model control group (x2 =4.122,P＜0.05).After 7 days and 14 days of injection,the liver function and TNF-α levels were statistically different between experimental group and model control group (both P ＜0.05),and liver pathology improvement in experimental group was more significant than model control group.DAPI labeled cells increased after transplantation in experimental group, while few DAPI labeled cells were observed in normal control group.Conclusions MSC can home to liver of FHF rats after MSC allogeneic transplantation through caudal veins,which can improve liver immunity and liver tissue necroinflammation,and facilitate recovery of liver function.Therefore,it is demonstrated that MSC transplantation has obvious therapeutic effect on rat FHF.