摘要目的 探讨蛛网膜下腔移植骨髓间充质干细胞(MSCs)对大鼠慢性神经病理性痛的影响.方法 雌性SD大鼠140只,体重180～200 g,采用坐骨神经分支选择损伤(SNI)法制备慢性神-经病理性痛模型,术后2周,随机分为4组(n=35):模型组(NP组)、MSCs组、PBS组和骨髓未贴壁单核细胞组(BNMCs组).MSCs组、PBS组、BNMCs组蛛网膜下腔分别注射1×105/μl的第3代MSCs悬液10μl、PBS 10μl、1×105/μl的BNMCs悬液10μl.于术前、术后2周、移植后1、2、3、4、5周(T0-6)时测定机械痛阈.同时于T1～6时测定痛阈后随机选择5只大鼠取脊髓腰膨大组织,使用RT-PCR法测定脑源性神经营养因子(BDNF)mRNA表达.结果 与T0时比较,T1时各组机械痛阈降低,T2～6时NP组、PBS组、BNMCs组机械痛阈降低(P＜0.05).与T1时比较,MSCs组T2～6时机械痛阈升高,T2-4时BDNF mRNA表达上调(P＜0.05),PBS组和BNMCs组其余时点各指标差异无统计学意义(P＞0.05).与NP组比较,MSCs组机械痛阈升高,BDNFmRNA表达上调(P＜0.05),PBS组和BNMCs组各指标差异无统计学意义(P＞0.05).结论 蛛网膜下腔移植MSCs可减轻大鼠慢性神经病理性痛,其机制可能与上调脊髓BDNF mRNA表达有关.

abstractsObjective To investigate the effect of transplantation of bone marrow mesenchymal stem cells (MSCs) in subarachnoid space on chronic neuropathic pain in rats. Methods One hundred and forty female SD rats weighing 180-200 g were used in this study. Chronic neuropathic pain (NP) was induced by ligation and separation of tibial and common fibular nerves (SNI). Two weeks after the surgery the animals were randomly divided into4 groups (n=35 each):group Ⅰ NP; group Ⅱ NP+ MSC (MSCs); group Ⅲ NP+ phosphate buffer saline (PBS) and group Ⅳ NP+ bone marrow monocyte (BNMCs). MSCs 10 μl, PBS 10 μl and BNMCs 10 μl were injected into subaraclmoid space at 2 weeks after surgery in group Ⅱ , Ⅲ and Ⅳ respectively. Paw withdrawal threshold to yon Frey filament stimulation (PWT) was measured before surgery (T0, baseline), at 2 weeks after surgery (T1) and 1, 2, 3, 4 and 5 weeks after subarachnoid injection (T2-6). Five animals were killed at T1-6 in each group and their lumbar enlargements were removed for determination of BDNF mRNA expression. Results PWT was significantly decreased by SNI at T1 in all 4 groups, and at T2-6 in group Ⅰ , Ⅲ and Ⅳ as compared with the baseline at T0 (P ＜ 0.05). Subarachnoid MSC transplantation significantly reduced mechanical hyperalgesia at T2-6 and up-regulated BDNF mRNA expression at T2-4 as compared with that at T1 (P ＜0.05). There was no significant change in PWT and BDNF mRNA expression after subarachnoid PBS and BNMCs injection in group Ⅲ and Ⅳ (P ＞ 0.05). Compared with group Ⅰ , PWT was significantly increased and BDNF mRNA expression was up-regulated in group Ⅱ (P ＜ 0.05), but no significant change in PBS and BNMCs was found in group Ⅲ (P ＞ 0.05) .Conclusion Up-regulation of BDNF mRNA expression in the spinal cord may be involved in the amelioration of chronic neuropathic pain by subarachnoid bone marrow mesenchymal stem cell transplantation.