摘要:Objective To investigate the effect of different transplantation approaches of human umbilical cord menchymal stem cells (HU-MSCs) on repairing hepatic ischemia-reperfusion injury (HIRI) in rat models. Methods Forty male SD rats were randomly divided into the A (control group), B (model group), C (portal vein transplantation of MSC sgroup) and D (tail vein transplantation of MSCs group) groups (n=10 for each group). In the B, C and D groups, HIRI rat models were established by Pringle maneuver. MSC transplantation was not delivered in the B group, and chloromethylbenzamidodialkylcarbocyanine(CM-DiL) labeled-HU-MSCs (106) were transplanted via portal vein or tail vein in the C or D groups. Blood samples were collected for detection of the expression levels of alanine aminotransferase(ALT) and tumor necrosis factor (TNF)-α before and 1, 3 and 5 d after transplantation. At 5 d post-transplantation, all rats in each group weresacrificed. The liver tissues were prepared for hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase-mediateddUTP nick end labeling(TUNEL) staining for evaluation of liver injury. The distribution of HU-MSCs in the rat liver in eachgroup was observed under laser confocal microscope. Results After HU-MSCs transplantation, the expression levels ofALT in the C and D groups were significantly down-regulated compared with that in the B group, and the level of ALT inthe C group was significantly lower than that in the D group (all P<0.05). The expression levels of inflammatory cytokineTNF-α in the C and D groups were significantly lower than that in the B group and the TNF-α level in the C group wasconsiderably lower than that in the D group (all P<0.05). HE staining of the liver tissue prompted that the liver injury was the most severe in the B group, and the liver injury in the C group was less severe compared with that in the D group. TUNEL staining of the liver tissue revealed that the apoptosis index (AI) in the C and D groups was significantly lower than that in the B group, and the AI in the C group was significantly lower compared with that in the D group (all P<0.05). Under laser confocal microscope, CM-DiL-labeled HU-MSCs were noted in the C and D groups after transplantation, and the quantity of HU-MSCs in the C group was significantly higher than that in the D group (all P<0.05). Conclusions Transplantation of HU-MSCs can mitigate the severity of HIRI. And transplantation via portal vein transplantation yields higher clinical efficacy compared with the tail vein route.%目的 探讨不同途径移植人脐带间充质干细胞(HU-MSCs)对大鼠肝脏缺血-再灌注损伤(HIRI)的修复效果.方法 将40只雄性SD大鼠随机分为A组(对照组)、B组(模型组)、C组(门静脉移植干细胞组)、D组(尾静脉移植干细胞组),每组10只,B、C、D组采用Pringle法建立HIRI模型,其中B组不予进行干细胞移植,C组和D组分别经门静脉、尾静脉移植氯甲基苯甲酰氨(CM-DiL)标记的HU-MSCs 106个.分别于术前、移植后第1、3、5日抽血检测丙氨酸转氨酶(ALT)、肿瘤坏死因子(TNF)-α 水平;移植后第5日处死各组大鼠,肝脏取材行苏木素-伊红(HE)及dUTP缺口末端标记(TUNEL)染色观察肝脏损伤情况,在激光共聚焦显微镜下观察HU-MSCs在各组大鼠肝脏分布情况.结果 干细胞移植后C、D组ALT水平较B组降低,且C组ALT水平低于D组(均为P<0.05);C、D组炎症因子TNF-α 水平明显低于B组,且与D组相比,C组下降更显著(均为P<0.05).肝组织HE染色提示B组肝脏损伤最严重,C组肝脏损伤轻于D组.肝组织TUNEL染色结果显示,C、D组的凋亡指数(AI)低于B组,且C组较D组低,差异均有统计学意义(均为P<0.05).激光共聚焦显微镜下可见,移植后C组与D组均可见CM-DiL标记的HU-MSCs,且C组的HU-MSCs数量高于D组(P<0.05).结论 移植HU-MSCs能减轻HIRI,且门静脉移植效果优于尾静脉移植效果.