黄芩苷通过抑制小胶质细胞活化缓解吗啡耐受

宋华园; 周丹丽; 韩园; 刘文涛

doi:10.11665/j.issn.1000-5048.20140317

黄芩苷通过抑制小胶质细胞活化缓解吗啡耐受

1.
南京医科大学江苏省神经退行性疾病重点实验室
2.
中国药科大学临床药学教研室
3.
徐州医学院江苏省麻醉学重点实验室

基金项目: 国家自然科学基金资助项目( No.81200860,81171044)

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出版历程
- 刊出日期: 2014-06-24

Baicalin attenuates morphine tolerance through suppressing spinal microglia activation in mice

摘要

摘要: 探讨黄芩苷对小胶质细胞活化和慢性耐受的影响并考察其作用机制。应用RT-PCR和ELISA法考察细胞释放炎症因子IL-1β和TNF-α的变化，Western blot法检测细胞中p-p38MAPK和IBA-1蛋白表达变化，热板法检测慢性吗啡耐受小鼠热板痛阈变化。实验结果发现，黄芩苷(1，10，100 μmol/L)剂量依赖性地抑制吗啡活化的BV2细胞释放IL-1β和TNF-α，100 μmol/L黄芩苷明显降低p-p38MAPK水平。鞘内注射黄芩苷(20，40，60 μg)可剂量依赖性地改善慢性吗啡耐受，鞘内注射黄芩苷60 μg可模拟出小胶质细胞抑制剂米诺环素的作用并能显著抑制慢性吗啡耐受小鼠脊髓p-p38MAPK以及IBA-1的表达。本研究表明，黄芩苷可通过抑制p38MAPK信号通路抑制吗啡引起的小胶质细胞活化，进而显著改善慢性吗啡耐受。
- 黄芩苷 /
- 吗啡 /
- 小胶质细胞 /
- 慢性耐受
Abstract: The aim of the present study was to investigate the effects and possible mechanisms of baicalin on morphine induced microglia activation and morphine tolerance. Cytokine IL-1β and TNF-α expression were analyzed by reverse transcription polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA), and the level of p38 MAP kinase phosphorylation and IBA-1 expression was determined by Western blot, the antinociception and morphine tolerance were assessed in mice using hot-plate test. Results showed that baicalin(1, 10, 100 μmol/L)inhibited morphine induced up-regulated levels of IL-1β, TNF-α in BV-2 microglia cells in a dose-dependent manner; and that 100 μmol/L baicalin significantly inhibited the level of p38MAP kinase phosphorylation induced by morphine in BV2 microglia cells. Intrathecal(it. )injection of baicalin(20, 40, 60 μg)attenuated the development of chronic morphine tolerance in a dose-dependent manner. Baicalin(60 μg)mimicked the role of minocycline and significantly suppressed the level of p38MAP kinase phosphorylation induced bychronic morphine treatment and IBA-1expression in mice spinal cord. In conclusion, baicalin suppresses morphine-induced microglia activation through suppressing p38MAPK signaling, resulting in significant attenuation of morphine antinociceptive tolerance.
- baicalin /
- morphine /
- microglia /
- chronic tolerance

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参考文献(15)

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