Li Weiyan, Li Yongle, Zhu Sihai, Ji Qin, Shu Yinyin, Zhang Lidong, Liu Jian
Department of Anesthesiology, Nanjing College of Clinical Medicine, Southern Medical University, Nanjing210002, PR China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
Department of Anesthesiology, Nanjing College of Clinical Medicine, Southern Medical University, Nanjing210002, PR China; Department of Anesthesiology, Guangdong Women and Children Hospital, Guangzhou 510010, PR China.
Neurosci Lett. 2015 Jan 1;584:314-9. doi: 10.1016/j.neulet.2014.11.003. Epub 2014 Nov 6.
Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. In the present study, we sought to investigate whether rosuvastatin could alleviate morphine tolerance by attenuating the glia mediated neuroinflammation in the spinal cord. Using a rat model of L5 spinal nerve transection, on day 8 after surgery morphine (10 mg/kg) was injected subcutaneously twice daily for consecutive 10 days. On day 13, with the establishment of morphine tolerance, rosuvastatin (10 mg/kg) was given o.p. for 5 days. On day 18, lumbar spinal cord was collected immediately after last behavioral testing. The analgesic effect of morphine was determined as the percentage of maximal possible effect (%MPE) after a single morphine (4 mg/kg) injection via tail vein on day 8, 13, and 18. The MPE decreased significantly after administration of morphine to rats with neuropathy for 5 days. Rosuvastatin administration for 5 days could restore morphine antinociceptive effect significantly. Additionally, the activation of astrocytes, the phosphorylation of extracellular signal-regulated kinase 42/44 (ERK(42/44)) and the expressions of TNFα and IL-1β were inhibited significantly by rosuvastatin. Our data suggested that rosuvastatin was a promising choice to treat neuropathic pain in combination with morphine.
最近的研究表明，他汀类药物除了具有降脂特性外，还具有抗炎作用。在本研究中，我们试图研究瑞舒伐他汀是否可以通过减轻脊髓中胶质细胞介导的神经炎症来减轻吗啡耐受性。使用L5脊髓神经横断大鼠模型，术后第8天，每天皮下注射吗啡（10mg/kg）两次，连续10天。在第13天，随着吗啡耐受性的建立，给予瑞舒伐他汀（10mg/kg）口服，持续5天。在第18天，在最后一次行为测试后立即收集腰段脊髓。吗啡的镇痛作用通过在第8、13和18天经尾静脉单次注射吗啡（4mg/kg）后的最大可能效应百分比（%MPE）来确定。对患有神经病变的大鼠给予吗啡5天后，MPE显著降低。给予瑞舒伐他汀5天可显著恢复吗啡的抗伤害感受作用。此外，瑞舒伐他汀可显著抑制星形胶质细胞的激活、细胞外信号调节激酶42/44（ERK(42/44)）的磷酸化以及TNFα和IL-1β的表达。我们的数据表明，瑞舒伐他汀是与吗啡联合治疗神经性疼痛的一个有前景的选择。
