移植途径对大鼠骨髓间充质干细胞归巢及肝功能恢复的影响

Effect of transplantation approach on homing of bone marrow mesenchymal stem cells and recovery of liver function in rats

目的探讨移植途径对骨髓间充质干细胞(MSCs)归巢及促进肝切除大鼠肝再生的影响。方法建立肝切除大鼠模型,随机分为3组,即肝切除对照组、尾静脉移植组和门静脉移植组。移植组分别经尾静脉和门静脉注射DAPI标记的MSCs约1.5×106/只,分别于第3天和第9天后采血清检测肝功能,第9天处死大鼠取肝脏标本,并通过荧光显微镜观察两种移植途径对MSCs向肝脏迁移的影响。结果门静脉移植组(18.1±3.4)个细胞/100倍视野到肝脏归巢及定植的MSCs多于尾静脉移植组(7.6±2.0)个细胞/100倍视野,差异有统计学意义(P<0.01)。术后第9天各组大鼠肝功能均有好转,丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST)3组之间对比差异无统计学意义(F=2.822,1.046,P=0.057,0.365,P>0.05);但两移植组与单纯肝切除组比较血浆白蛋白(ALB)均有明显升高,差异具有统计学意义(F=6.259,P=0.006);尾静脉移植组与门静脉移植组两移植组之间相比,差异无统计学意义(P>0.05)。结论移植途径对MSCs归巢、定植到肝脏有一定影响,门静脉途径优于外周静脉,MSCs移植对肝大部切除大鼠肝功能恢复具有促进作用。

Objective To observe the effect of transplantation approach on homing of bone marrow mesenchymal stem cells and promoting liver regeneration in rats after hepatectomy. Methods Bone marrow mesenchymal stem cells （about 1.5×106 each rat） labeled with DAPI were injected via the tail or portal vein of rats after hepatectomy. Serum was collected to evaluate liver function on the 3rd day and the 9th day after hepatectomy. Animals were sacrificed on the 9th day to collect liver samples. Fluorescence microscopy was used to observe cell migration. Results The number of bone marrow mesenchymal stem cells homing to liver was significantly higher in the rats receiving transplantation via the portal vein than those via the tail vein （18.1 ± 3.4 vs 7.6 ± 2.0/HPF×100）. The difference was statistically significant （P 〈 0.01）. The liver function of all groups improved on the 9th day after hepatectomy. There were no significant difference in ALT and AST among three groups （F = 2.822, 1.046; P = 0.057, 0.365）. ALB of the two cell transplantation groups were significantly higher than control group （F = 6.259, P = 0.006 ）, while there were no significant difference between two cell transplantation groups （ P 〉 0.05 ）.Conclusions Transplantation approach may influence MSCs homing＇ to liver. The transplantation via the portal vein is superior to that via the tail vein. MSC transplantation to rats after major hepatectomy can promote recovery of liver function.