丹参酮ⅡA抑制奥沙利铂诱发周围神经病变大鼠神经生长因子的表达

Tanshinone ⅡA Inhibits Nerve Growth Factor Expression in Rats with Oxaliplatininduced Peripheral Neuropathy

目的观察丹参酮ⅡA对奥沙利铂诱发周围神经毒性大鼠的神经生长因子的抑制作用。方法30只健康Wistar大鼠随机分成3组,对照组、模型组、丹参酮防治组。除对照组外,其余各组均予以腹腔注射奥沙利铂(20 mg/kg)造模。防治组在造模前3天至造模后第7天持续给药;并利用神经电生理仪检测大鼠机械性痛阈和冷刺激性疼痛,Western blot检测脊髓背角神经中神经生长因子(nerve growth factor,NGF)的表达。结果造模后6 h大鼠机械性痛阈较对照组降低,冷刺激缩足时间缩短(P<0.05),并随着观察时间的延长,痛阈值明显下降,在72 h达到最低并一直持续1周;第7天检测各组大鼠脊髓背角神经元中NGF表达情况,模型组较对照组明显降低;应用丹参酮ⅡA干预后,与模型组相比,大鼠机械性痛阈明显回升,对冷刺激耐受时间延长,NGF表达量明显增高(P<0.05)。结论丹参酮ⅡA可能是通过提高NGF的表达,发挥防治奥沙利铂诱导的周围神经病变的作用。

Objective To observe the inhibitory effect of Tanshinone ⅡA on the expression of nerve growth factor in rats with oxaliplatin-induced peripheral neurotoxicity(OXIPN). Methods Thirty healthy Wistar rats were randomly divided into three groups, normal control group, model group and Tanshinone ⅡA group. Except the control group, other Wistar rats were injected intraperitoneally with Oxaliplatin(20mg/kg). And the rats in Tanshinone ⅡA group were injected intraperitoneally with Tanshinone ⅡA from 3d before modeling to 7d after that; moreover, electrophysiology was used to examine the mechanical threshold and cold allodynia; Western blot was employed to detect the expression of nerve growth factor(NGF) in dorsal horn and dorsal root ganglion. Results Oxaplatin could reduce the mechanical threshold and cold allodynia at 6h after modeling(P<0.05); the mechanical threshold value was decreased with the extension of observation, and reached the lowest level at 72 h after modeling, which continued for 1 week. The expression of NGF in dorsal horn and dorsal root ganglion of model groups rats were signif icantly lower than those in control group at 7d after modeling; compared with model group, the mechanical threshold of rats were increased in TanshinoneⅡ A group, the tolerance of cold stimulation were prolonged, at meanwhile, the expression level of NSF was signif icantly up-regulated(P<0.05). Conclusion Tanshinon ⅡA could attenuated the oxaliplatin-induced neuropathic pain via increasing NGF level.