Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin.
Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin.
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DOI：
10.1016/j.neuro.2009.12.010
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发表时间：
2010-03
期刊：
影响因子：
3.4
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
James SE;Dunham M;Carrion-Jones M;Murashov A;Lu Q
化疗药物具有与治疗相关的神经毒性，当临床表现严重时，这可能成为剂量限制问题。然而，没有有效的疗法可以规避抗癌药物治疗的神经毒性。在这项研究中，我们利用新设计的顺铂诱导的周围神经病变小鼠模型来确定药物治疗引起的神经毒性的严重程度以及 Rho 激酶抑制剂 Y-27632 在治疗后恢复中的有效性。感觉神经传导研究显示，顺铂治疗后平均远端（峰值）潜伏期显着增加，表明感觉神经功能恶化。此外，随着顺铂累积剂量的增加，后爪触觉敏感性稳步下降。使用神经元标记蛋白基因产物 9.5 (PGP 9.5) 对腓肠神经进行的组织学和免疫组织化学分析表明，顺铂治疗的小鼠神经纤维形态异常。值得注意的是，Y-27632 治疗后改善了腓肠神经远端（峰值）潜伏期和感觉阈值，使其恢复到治疗前的水平。在恢复期间缺乏 Y-27632 的情况下，腓肠神经组织学恶化。这些研究表明，Rho 激酶抑制剂 Y-27632 可以在顺铂治疗后启动受损神经的再生。
Chemotherapy drugs have neurotoxicity associated with treatment, which can become a dose-limiting problem when clinical presentation is severe. However, there is no effective therapy to circumvent the neurotoxicity of anti-cancer drug treatment. In this study, we utilized a newly designed mouse model of cisplatin-induced peripheral neuropathy to determine both the severity of neurotoxicity induced by drug treatment and the effectiveness of the Rho kinase inhibitor Y-27632 in post-treatment recovery. Sensory nerve conduction studies revealed a significant increase in mean distal (peak) latency with cisplatin treatment, indicating a deterioration of sensory nerve function. Also, hind paw touch sensitivity decreased steadily with increasing cumulative dose of cisplatin. Histological and immunohistochemical analyses of the sural nerve using neuronal marker protein gene product 9.5 (PGP 9.5) demonstrated abnormal nerve fiber morphology in cisplatin-treated mice. Remarkably, post-treatment with Y-27632 improved the sural nerve distal (peak) latency and sensory threshold to return to pre-treatment levels. Sural nerve histology worsened in the absence of Y-27632 during recovery. These studies suggest that Rho kinase inhibitor Y-27632 can initiate regeneration of damaged nerves following cisplatin treatment.
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影响因子：
4.2
作者：
Brabeck, C;Beschorner, R;Schwab, JM
通讯作者：
Schwab, JM
DOI：
10.1073/pnas.072067999
发表时间：
2002-04-02
影响因子：
11.1
作者：
Einhorn, LH
通讯作者：
Einhorn, LH
影响因子：
3.4
作者：
Ta, Lauren E.;Espeset, Laura;Windebank, Anthony J.
通讯作者：
Windebank, Anthony J.
影响因子：
6.4
作者：
Wilder-Smith EP;Ong WY;Guo Y;Chow AW
通讯作者：
Chow AW
DOI：
10.2174/1568011053765967
发表时间：
2005-05-05
期刊：
Current Medicinal Chemistry - Anti-Cancer Agents
影响因子：
--
作者：
Sedletska, Yuliya;Giraud-Panis, Marie-Josephe;Malinge, Jean-Marc
通讯作者：
Malinge, Jean-Marc