含NR1亚基的NMDA受体在骨癌痛大鼠痛觉过敏中的作用

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目的:评价含NR1亚基的NMDA受体在骨癌痛大鼠痛觉过敏中的作用。方法:清洁级健康雄性Wistar大鼠24只,6周龄,体重200~230 g,采用随机数字表法分为3组(n n=8):假手术组(Sham组)、骨癌痛组(BCP组)和NR1 siRNA组(NR1组)。采用左侧胫骨骨髓腔注射乳腺癌Walker 256细胞混悬液制备大鼠骨癌痛模型。于造模开始后第10天,NR1组大鼠鞘内注射1 nmol/10 μl NR1 siRNA 10 μl,每48 h给药1次,连续4次。于造模前1 d (Tn 0)、造模后12~18 d (Tn 1~7)时每天固定时间行热板实验和甩尾实验,于Tn 7时行为学测试结束后处死大鼠取Ln 1~4脊髓组织,采用RT-PCR法测定NR1 mRNA的表达。n 结果:与Sham组相比,BCP组Tn 1~7时舔后足潜伏期缩短(n P<0.05);与BCP组相比,NR1组Tn 1~7时舔后足潜伏期延长,Tn 2,7时甩尾潜伏期延长,Tn 7时脊髓NR1 mRNA表达下调(n P<0.05)。n 结论:含NR1亚基的NMDA受体参与了骨癌痛大鼠痛觉过敏的形成和维持。“,”Objective:To evaluate the role of NR1 subunit-containing N-methyl-D-aspartate receptor (NMDAR) in hyperalgesia induced by bone cancer pain (BCP) in rats.Methods:Twenty-four clean-grade male Wistar rats, aged 6 weeks, weighing 200-230 g, were divided into 3 groups (n n=8 each) using a random number table method: sham operation group (Sham group), BCP group and NR1 siRNA group (NR1 group). BCP was induced by inoculating Walker 256 mammary gland carcinoma suspension into the medullary cavity of the left tibia.On the 10th day after establishing the model, 1 nmol/10 μl NR1 gene siRNA 10 μl was intrathecally injected every 48 h for 4 consecutive times in NR1 group.Hot plate test and tail flick test were performed at 1 day before establishing the model (T n 0), and 12-18 days after establishing the model (Tn 1-7). The animals were sacrificed after the end of behavioral test at Tn 7, and the lumbar segments of spinal cord (Ln 1-4) were removed for determination of the expression of NR1 mRNA by real-time polymerase chain reaction.n Results:Compared with Sham group, the latency to hind-paw licking was significantly shortened at Tn 1-7 in BCP group (n P<0.05). Compared with BCP group, the latency to hind-paw licking was significantly prolonged at Tn 1-7, the tail-flick latency was prolonged at Tn 2, 7, and the expression of NR1 mRNA was down-regulated in NR1 group (n P<0.05).n Conclusion:NR1 subunit-containing NMDAR is involved in the development and maintanence of hyperalgesia induced by BCP in rats.
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