鞘内移植hPPE修饰INPC对大鼠慢性神经病理性疼痛的镇痛效应  

Analgesic effect of intrathecally transplanted immortalized neural progenitor cells modified with human preproenkephalin gene on chronic neuropathic pain in rats

作　　者：高峰[1] 田玉科[1] 杨辉[1] 安珂[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉学教研室,武汉市430030 [2]中山大学附属第一医院麻醉科

出　　处：《中华麻醉学杂志》2007年第3期264-267,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目（30170905）

摘　　要：目的评价人前脑啡肽原基因（hPPE）修饰永生化大鼠神经前体细胞（INPC）对大鼠慢性神经病理性疼痛的镇痛效应。方法成年雌性Wistar大鼠40只,随机分为5组,Naive组大鼠不进行任何处理;Sham组大鼠仅暴露右侧坐骨神经分支;SNI组大鼠右侧后肢行保留性神经损伤（SNI）手术; INPC组和INPC/hPPE组大鼠分别于SNI术后1周鞘内移植5-溴脱氧尿嘧啶核苷（5-BrdU）标记的INPC或INPC/hPPE细胞。持续观察大鼠疼痛行为学,分别于SNI术前,SNI术后1周～细胞移植后8周内每周测定大鼠50％机械缩爪阈值（MWT）和热缩爪潜伏期（TWL）。于细胞移植后8周,取大鼠L（4～6）脊髓组织,测定移植细胞5-BrdU、亮氨酸脑啡肽的表达,测定hPPE mRNA表达和亮氨酸脑啡肽的分泌。结果与Naive组比较,SNI组、INPC组SNI术后1周大鼠出现疼痛行为学改变,MWT和TWL降低,并持续到细胞移植后8周;细胞移植后1周,INPC/hPPE组大鼠痛觉异常症状明显减轻,MWT和TWL升高,到细胞移植后2周已基本恢复至正常水平。INPC组和INPC/hPPE组脊髓背角软脑膜和浅层中均可检测到5-BrdU免疫染色阳性细胞;INPC/hPPE组hPPE mRNA表达和亮氨酸脑啡肽的水平高于其它4组（P＜0．05）。结论SNI诱导的慢性神经病理性疼痛大鼠鞘内移植hPPE修饰INPC后,可持续分泌高水平的亮氨酸脑啡肽,产生明显的镇痛效应。Objective To evaluate the analgesic effect of intrathecally transplanted immortalized neural progenitor cells （INPCs） modified with human preproenkephalin gene （hPPE） on chronic neuropathic pain. Methods Forty adult female Wistar rats weighing 150-200 g were randomly divided into 5 groups： T blank control group; Ⅱ sham operation group; Ⅲspared nerve injury （SNI） group; Ⅳ INPC group and ⅤINPC/hPPE group. In group Ⅳ and Ⅴ INPCs and INPC/hPPE were preincubated with 5-bromodeoxyuridine （5-BrdU） and transplanted intrathecally one week after right side SNI. Paw withdrawal threshold to mechanical （MWT） and thermal stimulation （TWL） were measured before SNI （baseline） and once a week from 1 week after SNI to 8 weeks after intrathecal（IT） cell transplantation. Lumbar segment of spinal cord （L4-6） was removed 8 weeks after IT cell transplantation for determination of 5-BrdU and Leu-enkephalin （L-EK） expression, hPPE mRNA expression and L-EK content in the spinal cord. Results Allodynia behavior and decrease in MWT and TWL were observed 1 week after SNI. The SNI-induced mechanical allodynia was significantly alleviated and MWT and TWL returned to the baseline level at the 2nd week after cell transplantation in INPC/hPPE group. Cells positively stained for 5-BrdU could still be found on the surface of dorsal horn at 8 weeks after cell transplantation. The expression of hPPE mRNA and the level of L-EK were significantly higher in INPC/hPPE group than in other groups （P 〈 0.05 ）. Conclusion INPC with hPPE can survive fairly long after IT transplantation and release high level of L-EK continuously and alleviate hyperalgesia.

关 键 词：干细胞移植 脑啡肽类 神经痛 注射 脊髓 

分 类 号：R686[医药卫生—骨科学]