高压氧联合骨髓间充质干细胞移植修复缺氧缺血性脑损伤

背景：单纯骨髓间充质干细胞移植对脑梗死组织的修复作用并不理想，需要结合药物及生物工程材料等手段进行综合治疗。目的：验证高压氧结合骨髓间充质干细胞移植修复大鼠缺氧缺血性脑损伤的效果。方法：体外培养大鼠骨髓间充质干细胞。应用线栓法建立大脑中动脉阻塞大鼠模型，按随机区组法分为3组，即对照组、骨髓间充质干细胞移植组及高压氧+骨髓间充质干细胞移植组。静脉移植后24 h，3 d及伤后1，2 周行Longa行为学评分，检测神经功能的损伤情况。移植2周后，应用RT-PCR法测定生长相关蛋白43 mRNA的表达，并以BrdU免疫组化和苏木精-伊红染色行梗死处组织学检查以证实恢复程度。结果与结论：移植后1周，高压氧+骨髓间充质干细胞移植组大鼠神经功能障碍评分低于骨髓间充质干细胞移植组，骨髓间充质干细胞移植组低于对照组(P < 0.05)。2周后脑梗死周围组织生长相关蛋白43 mRNA的表达高压氧+骨髓间充质干细胞移植组高于骨髓间充质干细胞移植组，骨髓间充质干细胞移植组高于对照组(P < 0.05)。BrdU免疫组化和苏木精-伊红切片中的神经元数量高压氧+骨髓间充质干细胞移植组多于骨髓间充质干细胞移植组，骨髓间充质干细胞移植组多于对照组(P < 0.05)。提示高压氧联合骨髓间充质干细胞静脉移植治疗大鼠缺氧缺血性脑损伤可明显改善大鼠的神经功能，效果优于单纯骨髓间充质干细胞移植。

Treatment of hypoxic-ischemic brain damage by hyperbaric oxygen combined with bone marrow mesenchymal stem cells transplantation

BACKGROUND: The repair effect of single bone marrow mesenchymal stem cells (BMSCs) transplantation on treating cerebral infracted tissues are poor, which need to be combined with drugs and bioengineered materials. OBJECTIVE: To determine whether the hyperbaric oxygen (HBO) treatment can enhance curative effects of BMSCs transplantation on hypoxic-ischemic brain damage in rats. METHODS: Rat BMSCs were cultured by the suspension culture in vitro. The models of cerebral infarction were made by middle cerebral artery occlusion (MCAQ). Rats were divided randomly into control group, BMSCs group and HBO+BMSCs group. The neurobehavioral scores were determined after 24 hours, 3 days and 1, 2 weeks after MCAQ. After 2 weeks, RT-PCR was used to assess the GAP-43 gene expression. The recovery condition was detected by BrdU immunohistochemistry and pathology. RESULTS AND CONCLUSION: The neurobehavioral scores were significantly lower in the HBO+BMSCs group than those in control group and BMSCs group at 1 week after MCAQ (P < 0.05). The expression of GAP-43 mRNA was highest in the HBO+BMSCs group, a few in the BMSCs group and lowest in the control group (P < 0.05). The number of neurons in the HBO+BMSCs group was higher than that in BMSCs group and control group (P < 0.05). Hyperbaric oxygen treatment combined with BMSCs transplanted by vein into the hypoxic-Ischemic brain damage tissues can significantly improve the neurological function in the rats with MCAQ, the curative effects is superior to single BMSCs transplantation.