摘要
目的探讨骨髓间充质干细胞（BM—MSC）在缺血再灌注（I／R）扩大肝切除（85％）大鼠模型中对肝功能衰竭的防治作用。方法以雄性SD大鼠提取和培养BM—MSC。8周龄雄性SD大鼠尾静脉注射BM—MSC或等量磷酸缓冲盐（PBS）后Pringle法肝门阻断30min，然后行85％的肝切除术。以假手术组为空白对照。观察手术后7天内的大鼠生存率，评估术后第2天肝再生状态及术后24h肝功能损害、肝细胞凋亡和残肝细胞因子的表达等。治疗组及假手术组分别输注荧光染料标记的BM—MSC，以观察BM—MSC最终的募集器官。结果绝大多数BM—MSC募集于脾。缺血前BM-MSC移植降低肝髓过氧化物酶水平[（19．9±6．0）mg／g比（41．4±10．2）mg／g湿组织]、下调促炎细胞因子。BM—MSC输注显著降低术后血清ALT和AST水平[AST（1475±275）IU／L比（25504-441）IU／L，P〈0．05；ALT（738±101）IU／L比（1113±268）IU／L，P〈0．05]，肝细胞凋亡明显减少，术后24h肝组织Suzuki评分显著降低。此外，BM—MSC治疗组术后肝重增加明显，肝细胞Ki67标记率显著高于对照组，提示BM—MSC可显著促进残肝再生。治疗组大鼠生存率也得到了明显改善（95％比70％，P〈0．05）。结论在I／R损伤及85％肝切除的动物模型中，BM—MSC输注不但可减轻I／R损伤，而且能显著促进肝细胞的再生，从而提高了生存率。
Objective To study the role of mesenchymal stem cells （MSC） in an animal model combining ischemia-reperfusion with 85% liver resection. Methods Eight-week-old male SD rats received BM-MSC by tail vein and then underwent 30-min ischemia followed by 85% liver resection. The survival rate was monitored for 7 days after surgery. Liver regeneration was assessed on day 2 after hepatectomy. Liver damage, liver cell apoptosis, and cytokine expression in the first 24 h after hepatectomy were also assessed. Results BM-MSC mostly homed to the spleen. Transplantation significantly inhibited myeloperoxidase [ （ 19.9 ± 6.0） mg/g vs. （ 41.4 ± 10.2 ） mg/g ] and downregulated proinflammatory cytokines. BM-MSC significantly reduced the ALT and AST levels [AST （ 1 475 ± 275 ） IU/L vs. （2 550 ± 441 ） IU/L, P 〈 0.05 ; ALT （738 ± 101 ） IU/L vs. （ 1 113 ± 268） IU/L, P 〈 0.05 ]. The attenuation of liver injury was also verified histologically 24 h after surgery. Liver cell apoptosis was markedly reduced. Moreover, BM-MSC infusion significantly promoted remnant liver regeneration. As a result, the survival rate was improved by BM-MSC treatment in this model （95% vs 70% , P 〈 0.05 ）. Conclusion In an animal model combining ischemia-reperfusion with 85% liver resection, BM-MSC infusion attenuated liver injury and promoted hepatocyte regeneration, resulting in improved survival rate.
出处
《中华肝胆外科杂志》
CAS
CSCD
北大核心
2016年第8期546-551,共6页
Chinese Journal of Hepatobiliary Surgery
基金
全军保健专项课题（11BJZ13）
关键词
骨髓间充质干细胞
肝切除
缺血再灌注损伤
肝再生
Bone marrow-derived mesenchymal stem cell
Hepatectomy
Ischemia/reperfusion injury
Liver regeneration
