骨髓间充质干细胞移植对急性肝衰竭大鼠基质细胞衍化生长因子-1α、血管内皮生长因子表达的影响  

Effects of bone marrow mesenchymal stem cell transplantation on the expression of stromal cell-derived factor-1α and vascular endothelial growth factor in rats with acute hepatic failure

作　　者：袁淑芳[1] 刘志英[2] 阿依夏木古丽 郑嵘灵 张跃新[3] Yuan Shufang, Liu Zhiying, Ayi Xiamuguli, Zheng Rongjiong, Zhang Yuexin(Department of Infectious Diseases, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China; Department of Pathology, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China; Department of Infectious Diseases, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China)

机构地区：[1]新疆医科大学第五附属医院感染科,乌鲁木齐830011 [2]新疆医科大学第五附属医院病理科,乌鲁木齐830011 [3]新疆医科大学第一附属医院感染科,830011

出　　处：《中华肝脏病杂志》2018年第10期750-755,共6页Chinese Journal of Hepatology

基　　金：新疆维吾尔自治区自然科学基金（医学联合基金2015211C178）

摘　　要：目的探讨骨髓间充质干细胞（BMSCs）移植治疗急性肝衰竭大鼠的疗效、对比两种移植途径的疗效，以及对基质细胞衍化生长因子（SDF）-1α、血管内皮生长因子（VEGF）表达的影响。方法对84只-氨基半乳糖联合脂多糖诱导的急性肝衰竭（ALF）大鼠，随机平均分为对照组、尾静脉移植组、门静脉移植组，后两组通过尾静脉、门静脉注射同种异体大鼠BMSCs。于移植后24、72、120、168h收集血液样本和肝组织标本，检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平，比较BMSCs移植前后各组肝功能的改善情况。采用免疫荧光化学方法、Westernblot等方法检测肝组织VEGF、SDF-1α的表达情况。计量资料用方差分析进行组间比较，计数资料采用秩转换后的方差分析；相关分析采用Sperman等级相关分析。结果尾静脉移植、门静脉移植组中大鼠血清ALT、AST水平于移植后24h达峰值，分别为（134．60±58．08）U／L、（179．20±86．68）U／L和（131．00±54．47）U／L、（173．50±93．10）U／L；于移植后168h降至（4J6．10±8．40）U／L、（95．67±13．80）U／L和（19．30±1．30）U／L、（54．30±6．00）U／L。在BMSCs移植120、168h后，尾静脉移植组、门静脉移植组中血清AIJrr、AST水平与对照组相比，差异有统计学意义（F≥12．51，P值均〈0．01）。原位杂交、免疫荧光化学法结果显示：两种BMSCs移植组中SDF-1±、VEGF蛋白的表达水平随肝功能的好转逐渐升高，在移植后120、168h与对照组相比，差异有统计学意义∽≥9．069，尸值均〈0．05）。尾静脉和门静脉移植组间肝组织SDF-1±、VEGF蛋白的表达水平差异无统计学意义（P〉0．05）。相关分析显示肝组织中SDF-1±、VEGF表达水平呈正相关（r=0．923，P〈0．05）。结论BMSCs移植能够促进ALF大鼠肝功能的恢复，减轻肝组织炎症坏死程度；BMSCs�Objective To investigate the curative effect of bone marrow mesenchymal stem cells （BMSCs）transplantation on the expression of stromal cell-derived growth factor （SDF-1α） and vascular endothelial growth factor （VEGF） in rats with acute hepatic failure, and to compare the effects of two transplantation pathways. Methods Eighty-four rats with acute liver failure （ALF） induced by D-galactosamine combined with lipopolysaccharide were randomly divided into control group, tail vein and portal vein transplantation group. The latter two groups were injected allogenic BMSCs into the tail vein and portal vein. Blood samples and liver tissue samples were collected at 24, 72, 120, and 168h after transplantation to detect serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST）. The improvement of liver function before and after BMSCs transplantation was compared. The expression of VEGF and SDF-1α in liver tissue was detected by immunofluorescence and Western blot. Data measurement between two groups was performed by analysis of variance and the correlation analysis was performed by Spearman＇s rank correlation coefficient. Results Serum ALT and AST levels in the tail vein and portal vein transplantation group peaked at 24 h after transplantation, which were （134.60 ± 58.08 1U/L）, （179.20 ±86.68 IU/L）, and （131.00 ± 54.47 IU/L）, （173.50 ± 93.10 IU/L）. In addition, 168h after transplantation it decreased to （46.10 ± 8.40 IU/L）, （95.67 ± 13.80 IU/L） and （19.30± 1.30 IU/L）, （54.30 ± 6.00 IU/L）. After 120 and 168 hours of BMSCs transplantation, the levels of serum ALT and AST in tail vein and portal vein transplantation group were significantly higher than control group （F ≥ 12.51, P 〈 0.01）. The results of western blot and immunofluorescence showed that the expression levels of SDF-1α and VEGF protein in the two BMSCs transplantation groups increased with the improvement of liver function, and the difference was statistically significant

关 键 词：肝功能衰竭 急肚 干细胞 基质细胞衍化生长因子-1α 血管内皮生长因子 

分 类 号：R575.3[医药卫生—消化系统]