摘要
Objective Cisplatin exerts its cytotoxic effect through distinct DNA lesions,leading to peripheral neuropathy.The risk of sensory neuropathy is a common problem during cancer treatment with cisplatin,leading to somatic hyperalgesia.Yet,data focussing on cisplatin-induced impairment of the autonomic nervous system are limited.The present study was aimed to investigate the effect of recombinant human erythropoietin（rhEPO）on cisplatin-induced visceral hyperalgesia.Methods C57BL/6 mice were treated either with cisplatin（2 mg/kg,once per week）or with cisplatin（2 mg/kg,once per week）plus rhEPO （40μg/kg,3 times per week）for 8 weeks.Controls were treated with saline.To quantify the visceromotor response（VMR）at week 9,standardized electrodes were implanted into the external oblique musculature for electromyographic recordings.After that,animals were decapitated and dorsal root ganglia（DRG）was removed for transmission electron microscopy studies.Results Cisplatin-treated mice showed a significant increase of VMR compared to the controls[（7080±969）vs（2864±279）;P0.001],while rhEPO dramatically counteracted this effect[（2962±336）vs（7080±969）;P0.001）].Transmission electron microscopy revealed cisplatin-induced structural lesions of nuclear membrane in DRG cells,which could be ameliorated by rhEPO.Conclusion Erythropoietin can significantly ameliorate the cisplatin-induced visceral hyperplasia and DRG nuclear membrane structure damage in mice,indicating a neuroprotective role of erythropoietin.
目的顺铂是肿瘤化疗的常用药物,主要通过损伤细胞DNA发挥细胞毒性作用。在肿瘤治疗过程中,顺铂往往会引起周围神经病变,进而导致痛觉增敏。本文就重组人红细胞生成素(recombinant human erythropoietin,rhEPO)是否能抑制顺铂引起的内脏痛觉增敏进行研究。方法C57BL/6系小鼠经顺铂或顺铂与rhEPO共同作用8周后,用肌电检测法观察在结肠直肠扩张性刺激下内脏运动的变化,并用透射电子显微镜观察背根神经节细胞结构水平的变化。结果顺铂能显著增强结肠直肠扩张性刺激下小鼠的内脏运动反射,而rhEPO则能显著减轻这一作用。此外,透射电子显微镜观察显示rhEPO能显著减轻顺铂引起的背根神经节细胞核膜损伤。结论促红细胞生成素具有神经保护作用。
