LV-GlyT2 siRNA对骨癌痛大鼠吗啡耐受形成的影响  

Intrathecal injection of LV-GlyT2-RNA attenuates morphine tolerance of rats with bone cancer pain

作　　者：徐伟 王健 丁卓峰 李珍[1] 张洁[1] Wei Xu;Jian Wang;Zhuo-feng Ding;Zhen Li;Jie Zhang(Department of Anesthesiology,Maternal and Child Health Care Hospital,Hunan Province,Changsha,410008,China;Department of Anesthesiology,Xiangya Hospital,Central South University,Changsha,Hunan,410008,China)

机构地区：[1]湖南省妇幼保健院麻醉科,湖南长沙410008 [2]中南大学湘雅医院麻醉科,湖南长沙410008

出　　处：《中国现代医学杂志》2020年第20期1-5,共5页China Journal of Modern Medicine

基　　金：国家自然科学基金青年基金(No:81901143)。

摘　　要：目的观察鞘内注射GlyT2 siRNA慢病毒载体(LV-GlyT2 siRNA)对骨癌痛大鼠吗啡耐受形成的影响。方法将骨癌痛模型大鼠随机分为生理盐水组(NS组)、阴性对照病毒组(LV-NC组)和阳性病毒组(LV-GlyT2 siRNA组),每组10只。骨癌痛第7天,3组大鼠分别鞘内注射生理盐水、阴性对照病毒(LV-NC)及GlyT2 siRNA慢病毒载体(LV-GlyT2 siRNA);骨癌痛第9天开始大鼠均鞘内注射吗啡,连续7d。分别于癌细胞接种前及接种后7d测量大鼠术侧后肢机械缩足阈值(MWT);注射吗啡后1d、3d、5d、7d测量大鼠甩尾潜伏期,并计算%MPE值;注射吗啡第7天采用Western blotting检测脊髓GlyT2蛋白的表达。结果 3组大鼠癌细胞接种前及接种后7d的术侧后肢MWT在不同时间上有差异(P<0.05),不同组间及变化趋势无差异(P>0.05)。3组大鼠接种后7d的MWT较接种前下降(P<0.05)。3组大鼠注射吗啡后1d、3d、5d、7d的%MPE在不同时间、不同组间及变化趋势上有差异(P<0.05),注射吗啡后5d和7d,LV-GlyT2 siRNA组大鼠%MPE值较其他组升高(P<0.05)。LV-GlyT2 siRNA组GlyT2蛋白相对表达量低于LV-NC组和NS组(P<0.05)。结论下调GlyT2表达可缓解骨癌痛大鼠吗啡耐受的形成。Objective To investigate the effect of intrathecal injection of lentiviral vector mediated GlyT2 siRNA on the development of morphine tolerance in bone cancer pain rats.Methods Female adult rats were used to establish bone cancer pain mode (BCP) by injecting Walker 256 breast tumor cell (TCI),normal saline,lentiviral vector mediated GlyT2 siRNA,negative control were intrathecally injected on 7 day post cell infusion.Morphine was intrathecally injected for 7 consecutive days to induce morphine tolerance from day 9 after cell infusion.Before BCP and 7 days after BCP modeling,the MWT was performed to assess the rats’ pain behavioral changes and %MPE was calculated to evaluate the development of morphine tolerance,western blotting was used to detect the expression of GlyT2 protein.Results After TCI,the MWTs of all groups were significantly decreased on day 7,compared with day 1 (P<0.05).After intrathecal injection of morphine,the %MPE of LV-GlyT2-siRNA was increased significantly compared with other groups (P<0.05),and the GlyT2 expression was downregulated in the spinal cord of LV-GlyT2-siRNA (P<0.05).Conclusion Downregulation of GlyT2 can attenuate morphine tolerance of rats with bone cancer pain.

关 键 词：骨肿瘤 疼痛 GlyT2 慢病毒载体 吗啡 大鼠 

分 类 号：R738.1[医药卫生—肿瘤]