Tanshinone ⅡA Inhibits Nerve Growth Factor Expression in Rats with Oxaliplatininduced Peripheral Neuropathy
-
摘要: 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。Abstract: 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 72h after modeling, which continued for 1 week. The expression of NGF in dorsal horn and dorsal root ganglion of model groups rats were significantly 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 significantly up-regulated (P<0.05). Conclusion Tanshinon ⅡA could attenuated the oxaliplatin-induced neuropathic pain via increasing NGF level.
-
Key words:
- TanshinoneⅡA /
- Oxaliplatin /
- Peripheral neuropathy /
- Nerve growth factor
-
-
[1] Brouwers EE, Huitema AD, Boogerd W, et al. Persistent neuropathy after treatment with cisplatin and oxaliplatin[J]. Acta Oncol, 2009, 48(6):832-41. [2] Aloe L, Rocco ML, Bianchi P, et al. Nerve growth factor: from the early discoveries to the potential clinical use[J]. J Transl Med, 20 12, 10: 239. [3] Jamieson SM, Liu J, Hsu T, et al. Paclitaxel induces nucleolar enlargement in dorsal root ganglion neurons in vivo reducing oxaliplatin toxicity[J]. Br J Cancer, 2003, 88(12): 1942-7. [4] Ko MH, Hu ME, Hsieh YL, et al. Peptidergic intraepidermal nerve fibers in the skin contribute to the neuropathic pain in paclitaxelinduced peripheral neuropathy[J]. Neuropeptides, 2014, 48(3): 10 9-17. [5] Biane J, Conner JM, Tuszynski MH. Nerve growth factor is primarily produced by GABAergic neurons of the adult rat cortex[J]. Front Cell Neurosci, 2014, 8: 220. [6] Mysona BA, Shanab AY, Elshaer SL, et al. Nerve growth factor in diabetic retinopathy: beyond neurons[J]. Expert Rev Ophthalmol, 20 14, 9(2): 99-107. [7] Zhang H, Wu F, Kong X, et al. Nerve growth factor improves functional recovery by inhibiting endoplasmic reticulum stressinduced neuronal apoptosis in rats with spinal cord injury[J]. J Transl Med, 2014, 12: 130. [8] Engle DB, Belisle JA, Gubbels JA, et al. Effect of acetyl-lcarnitine on ovarian cancer cells proliferation, nerve growth factor receptor (Trk-A and p75) expression, and the cytotoxic potential of paclitaxel and carboplatin[J]. Gynecol Oncol, 2009, 112(3): 63 1-6. [9] Wang Y, Feng Y, Li J. Expression of NGF in dorsal horn and dorsal root ganglion of rats with paclitaxel-evoked neuropathic pain[J]. Zhongguo Teng Tong Yi Xue Za Zhi, 2013,19 (8): 472-7.[王莹, 冯艺, 李君. 神经生长因子在紫杉醇诱发神经病理性痛模型 大鼠脊髓背角和背根神经节中的表达[J]. 中国疼痛医学杂志, 20 13, 19(8): 472-7.] [10] Li OJ, Cui HJ, Huang MY, et al. Effect of Astragalus Root Injection on hippocampal neuronal apoptosis induced by axaliplatin[J]. Zhonghua Zhong Yi Yao Za Zhi, 2010, 25(1): 55 -8.[李欧静, 崔慧娟, 黄美燕, 等.黄芪注射液对奥沙利铂致海 马神经细胞凋亡的抑制作用[J]. 中华中医药杂志, 2010, 25(1): 55 -8.] [11] Descoeur J, Pereira V, Pizzoccaro A, et all. Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors[J]. EMBO Mol Med, 2011, 3(5): 26 6-78.
计量
- 文章访问数: 1022
- HTML全文浏览量: 309
- PDF下载量: 452
下载:
