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作者:

Hu, Chunsheng (Hu, Chunsheng.) | Lu, Yuxin (Lu, Yuxin.) | Cheng, Xiaochen (Cheng, Xiaochen.) | Cui, Yufang (Cui, Yufang.) | Wu, Zuze (Wu, Zuze.) | Zhang, Qinglin (Zhang, Qinglin.)

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摘要:

BackgroundNeuropathic pain (NP) is a refractory disease in the clinic with a tremendous impact on the quality of life of patients. Gene therapy is a potential strategy for the management of NP. In the present study, we examined the analgesic effect and mechanism of hepatocyte growth factor (HGF) in vitro and in vivo. MethodsWe examined the proinflammatroy gene changes in lipopolysaccharide (LPS)-induced microglia BV2 cells with a quantitative real-time polymerase chain reaction of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)- and inducible nitric oxide synthase (iNOS). Mechanical stimulation tests were performed five times at 5-min intervals to assess pain thresholds using Von Frey Hair in mice following spared nerve injury (SNI). The glial cell activation of spinal cord was examined by western blotting. Statistical significance was determined by a Tukey's test and a paired t-test. ResultsWe found that recombinant human HGF protein suppressed LPS-induced BV2 cell activation in vitro, marked by the down-regulation of IL-1, IL-6, TNF- and iNOS expression, as well as decrease of nitric oxide production. Moreover, intrathecal injection of naked plasmid encoding HGF gene (pUDK-HGF) significantly attenuated SNI-induced pain behaviors in mice by direct inhibition of spinal cord microglia and astrocyte activation. ConclusionsThe results of the present study indicate that pUDK-HGF can reduce cytotoxicity products released from activated glial cells, which may provide a promising therapeutic strategy for treating NP.

关键词:

hepatocyte growth factor microglia astrocyte gene therapy neuropathic pain

作者机构:

  • [ 1 ] [Hu, Chunsheng]Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China
  • [ 2 ] [Lu, Yuxin]Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China
  • [ 3 ] [Cheng, Xiaochen]Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China
  • [ 4 ] [Cui, Yufang]Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China
  • [ 5 ] [Wu, Zuze]Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China
  • [ 6 ] [Zhang, Qinglin]Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China
  • [ 7 ] [Hu, Chunsheng]Chongqing Univ Arts & Sci, Int Acad Targeted Therapeut & Innovat, Chongqing, Peoples R China
  • [ 8 ] [Hu, Chunsheng]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing, Peoples R China
  • [ 9 ] [Wu, Zuze]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing, Peoples R China

通讯作者信息:

  • [Zhang, Qinglin]Beijing Inst Radiat Med, 27 Taiping Rd, Beijing 100850, Peoples R China

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来源 :

JOURNAL OF GENE MEDICINE

ISSN: 1099-498X

年份: 2017

期: 12

卷: 19

3 . 5 0 0

JCR@2022

ESI学科: MOLECULAR BIOLOGY & GENETICS;

ESI高被引阀值:309

中科院分区:3

被引次数:

WoS核心集被引频次: 9

SCOPUS被引频次: 10

ESI高被引论文在榜: 0 展开所有

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