绿原酸拮抗顺铂诱发的神经病理性疼痛的机制研究

The mechanism of chlorogenic acid against neuropathic pain induced by cisplatin

本研究评价绿原酸能否抑制顺铂所致的化疗痛,并探讨其分子机制。实验方案遵循新乡市中心医院实验动物伦理委员会规定,所有程序均按照动物使用和护理的伦理原则进行。实验采用von Frey hair和热辐仪测定大鼠的机械痛阈和热痛阈,采用Western blot检测大鼠背根神经节(dorsal root ganglion,DRG)中辣椒素受体(transient receptor potential vanilloid type-1,TRPV1)的表达,采用膜片钳记录大鼠DRG神经元中TRPV1电流。实验结果表明,顺铂可诱导大鼠产生机械痛和热痛反应,而TRPV1受体拮抗剂capsazepine和绿原酸均可抑制顺铂介导的痛觉敏化;Western blot实验表明,顺铂可上调大鼠DRG中TRPV1蛋白的表达,而绿原酸则可以抑制顺铂对TRPV1蛋白的上调作用;膜片钳实验结果显示,顺铂可增加TRPV1电流密度,绿原酸可显著逆转顺铂的这种作用。以上结果表明,绿原酸可通过抑制TRPV1的表达和功能进而缓解顺铂诱发的化疗痛。

This study aimed to investigate the analgesic effect of chlorogenic acid on cisplatin-induced neuropathic pain and explored the underlying molecular mechanisms.The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Xinxiang Central Hospital,in compliance with the Institutional Animal Care Guidelines.Von Frey hair and a radiant heat was employed to measure mechanical allodynia and thermal hyperalgesia;Western blot was used to examine transient receptor potential vanilloid type-1(TRPV1)protein expression in the rat dorsal root ganglion(DRG);patch clamp was used to record TRPV1 currents in DRG neurons.The experimental results showed that chlorogenic acid could attenuate cisplatin-induce mechanical allodynia and thermal hyperalgesia in rats.The expression of TRPV1 protein in DRGs was increased in cisplatin-treated rats,while chlorogenic acid also could reverse cisplatin-induced the upregulation of TRPV1 protein.Forthermore,chlorogenic acid could attenuate cisplatin-mediated the upregulation of TRPV1 current density.These above results indicated that chlorogenic acid could alleviate cisplatin-induced pain hypersensitivity through inhibition of the expression and function of TRPV1 in rats.