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益肾活血止痛方对骨癌痛大鼠脊髓星形胶质细胞活化及p38 MAPK的影响
宋 程,任丽芝,唐 蔚
0
(湖南省肿瘤医院,湖南 长沙,410013;湖南省中医药研究院附属医院,湖南 长沙,410006)
摘要:
目的:探讨益肾活血止痛方的镇痛作用及对骨癌痛大鼠热缩足潜伏期(PWTL)、骨质破坏程度、骨密度及脊髓星形胶质细胞神经胶质纤维酸性蛋白(GFAP)和p38丝裂原活化蛋白激酶(p38 MAPK)表达的影响。方法:将40只大鼠随机分为中药组(1.92 g/ml)、唑来膦酸组(30 μg/kg)、假手术组、模型组,每组各10只。于大鼠左后肢体注射Walker-256细胞建立骨癌痛模型,于造模后第5天开始给药,连续21 d。并于造模后第7、14、21天检测PWTL,于造模后第22天采用X线检查各组大鼠骨质破坏程度及骨密度,并提取大鼠脊髓腰膨大处,采用荧光定量PCR及Western blot分别检测GFAP和p38 MAPK在mRNA及蛋白的表达情况。结果:行为学评估提示,造模后7、14、21天,中药组及唑来膦酸组PWTL值均高于模型组(P<0.05)。中药组、唑来膦酸组及模型组大鼠胫骨出现不同程度骨质破坏,且大鼠胫骨骨密度及骨矿物质水平均较模型组高(P<0.05)。中药组和唑来膦酸组GFAP mRNA、p-p38 MAPK mRNA及相应的蛋白含量均低于模型组(P<0.05)。结论:益肾活血止痛方的止痛机制可能与抑制脊髓星形胶质细胞活化,阻断中枢痛觉敏化MAPK通路有关。
关键词:  骨性癌痛  益肾活血止痛方  GFAP  p38 MAPK通路  实验研究
DOI:
Effect of Yishen Huoxue Zhitong prescription on spinal astrocyte activation and p38 mitogen-activated protein kinase in a rat model of bone cancer pain
SONG Cheng,REN Lizhi,TANG Wei
(Hunan Cancer Hospital,Changsha 410013,Hunan,China;The Affiliated Hospital of Hunan Academy of Chinese Medicine,Changsha 410006,Hunan,China)
Abstract:
Objective:To investigate the analgesic effect of Yishen Huoxue Zhitong prescription and its effect on paw withdrawal thermal latency (PWTL),degree of bone destruction,bone mineral density,and expression of glial fibrillary acidic protein (GFAP) and p38 mitogen-activated protein kinase (p38 MAPK) in spinal astrocytes in a rat model of bone cancer pain.Methods:A total of 40 rats were randomly divided into traditional Chinese medicine (TCM) group (1.92 g/ml),zoledronic acid group (30 μg/kg),sham-operation group,and model group,with 10 rats in each group.The rats were given the injection of Walker-256 cells at the left hindlimb to establish a model of bone cancer pain,and drug administration was started on day 5 after modeling and lasted for 21 consecutive days.PWTL was measured on days 7,14,and 21 after modeling,and X-ray examination was performed on day 22 to observe the degree of bone destruction and bone mineral density.Samples were collected from spinal cord lumbar enlargement,and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of GFAP and p38 MAPK.Results:Behavioral assessment showed that the TCM group and the zoledronic acid group had a significantly longer PWTL than the model group on days 7,14,and 21 after modeling (P<0.05).Varying degrees of bone destruction were observed in the TCM group,the zoledronic acid group,and the model group,and compared with the model group,the TCM group and the zoledronic acid group had significantly higher bone mineral density and bone mineral levels in the tibia (P<0.05).The TCM group and the zoledronic acid group had significantly lower mRNA and protein expression levels of GFAP and p38 MAPK than the model group (P<0.05).Conclusion:Yishen Huoxue Zhitong prescription may exert an analgesic effect by inhibiting spinal astrocyte activation,blocking pain sensation of the central nervous system,and sensitizing the MAPK pathway.
Key words:  bone cancer pain  Yishen Huoxue Zhitong prescription  glial fibrillary acidic protein  p38 mitogen-activated protein kinase pathway  experimental study

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