| 摘要: |
| 目的:观察人骨髓间充质干细胞(hMSCs)移植对缺氧缺血性脑损伤幼年大鼠脑功能影响及其在脑组织中的迁移、分化过程，探讨hMSCs移植对缺氧缺血性脑损伤的保护作用，为后续研究奠定基础。方法:大鼠随机分为hMSCs移植组(n=18)、移植对照组(n=18)、模型组(n=6)和假手术组(n=6)。前3组均建立幼年Wistar大鼠缺氧缺血性脑损伤(HIBD)模型，3 d后hMSCs移植组缓慢注射约5×105 个hMSCs至大鼠的左背侧海马，移植对照组注射等体积的磷酸盐缓冲液，假手术组和模型组未移植。其中hMSCs移植组和移植对照组又随机分为5组,分别于移植后0 d、3 d、1周、2周(均n=3)和4周(n=6)处死。模型组与假手术组均于造模后31 d(即移植后4周)处死。大鼠处死前均行交替电刺激Y迷宫行为学实验，处死后取脑组织行H-E染色观察病理变化；hMSCs移植组和移植对照组大鼠同时还行免疫组化染色检测hMSCs在脑内的分布。结果:免疫组化结果显示hMSCs移植后1周主要沿脑室系统迁移，部分沿胼胝体向对侧迁移，移植后4周细胞沿脑室向周围实质迁移，广泛分布于脑组织。Y迷宫实验显示hMSCs移植组总错误次数(TE)明显少于移植对照组(5.00±2.82 vs 12.67±3.72)，差异有统计学意义(P<0.05)，提示hMSCs移植组大鼠空间记忆能力显著优于移植对照组。H-E染色结果显示hMSCs移植组大鼠脑组织损伤较移植对照组及模型组轻。结论:hMSCs脑内移植后可在大鼠中枢神经系统内存活并迁移，且hMSCs移植能在一定程度上促进损伤脑组织和脑功能的恢复，值得进一步研究。 |
| 关键词: 人骨髓间充质干细胞 细胞移植 缺氧缺血 脑 |
| DOI：10.3724/SP.J.1008.2008.01009 |
| 投稿时间：2008-04-16修订日期：2008-08-04 |
| 基金项目:浙江省医学重点学科“组织工程学”,浙江科技厅重大科技攻关项目(2006C13022). |
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| Protective effect of intracerebral transplantation of human mesenchymal stem cells on hypoxic-ischemic brain damage in rats |
| FAN Jian-ling1,LAI Xiao-yu1,HUANG Li2,WANG Yan3,CAO Jun-li1,HUANG He1* |
| (1.Bone Marrow Transplantation Center,The First Affiliated Hospital,Zhejiang University,School of Medicine,Hangzhou 310003,China;2.Department of Hematology,The People’s Hospital of Jinhua,Jinhua 321000;3.Department of Pediatrics,The First Affiliated Hospital,Zhejiang Traditional Chinese Medicine University,Hangzhou 310053) |
| Abstract: |
| Objective:To explore the migration,differentiation and the therapeutic effect of intracerebral transplantation of human mesenchymal stem cells (hMSCs) after hypoxic-ischemic brain damage in rats,and to test whether three anti-hMSCs monoclonal antibodies prepared by our group can detect hMSCs in rat brains.Methods: hMSCs were isolated and purified by density gradient centrifugation and adherence to culture flask.Cells of passage 3-5 were prelabeled with bromodeoxyuridine (BrdU) for 72 h before transplantation.Animal models of hypoxic-ischemic brain damage (HIBD) were built with 1 month old Wistar rats.Three days after hypoxia-ischemia,HIBD rats in hMSCs-treated group (n=18) received intracerebral transplantation of 5×105 hMSCs.In control group (n=18) HIBD rats received phosphate buffered saline of the same volume.In sham-operated group (n=6) and HIBD group (n=6),rats did not receive any transplantation.Rats in hMSCs-treated group and control group were allowed to survive for 0 day,3 days,1 weeks,2 weeks (all n=3) and 4 weeks (n=6,after transplantation). |
| Key words: human mesenchymal stem cells cell transplantation hypoxia-ischemia brain |
