Yang X, Gong H, Liu Z, Liu H, Wang H, Li Zhenzhong
Department of Nephrology, Shandong University School of Medicine, Jinan, China.
Methods Find Exp Clin Pharmacol. 2010 Jan-Feb;32(1):3-11. doi: 10.1358/mf.2010.32.1.1444424.
The purpose of this study was to investigate the effects of capsaicin (CAP) and resiniferatoxin (RTX) on substance P (SP) release and transient receptor potential vanilloid type 1 (TRPV1) expression of cultured rat dorsal root ganglion (DRG) neurons. Dissociated DRG cells of embryonic 15-day-old Wistar rat were cultured for 3 days and then exposed to CAP (1 micromol/L, 10 micromol/L) or RTX (10 nmol/L, 100 nmol/L) for 10 min. At 3 days of culture growth, SP release increased significantly after 10 min of stimulation with CAP or RTX as compared with controls. Six days after acute exposure to CAP or RTX, SP release and SP expression of cultured rat DRG neurons decreased significantly in both CAP- and RTX-treated cultures as compared with controls. Preprotachykinin (PPT) mRNA, TRPV1 mRNA and TRPV1 protein expression decreased in CAP-treated cultures and RTX cultures treated with the higher concentration, whereas RTX cultures treated with the lower concentration were not affected. The results indicate that CAP and high concentrations of RTX are more neurotoxic to cultured rat DRG neurons while the inability of the neurons to express SP or TRPV1 after acute exposure to the lower concentration of RTX could be partially reversed after a period of incubation. The efficacy and therapeutic potential of the reversible action of RTX are more applicable as strategies for pain or neurogenic inflammation therapy.
本研究旨在探讨辣椒素（CAP）和树脂毒素（RTX）对培养的大鼠背根神经节（DRG）神经元中P物质（SP）释放及瞬时受体电位香草酸亚型1（TRPV1）表达的影响。将15日龄Wistar大鼠胚胎的DRG细胞解离后培养3天，然后分别用CAP（1 μmol/L、10 μmol/L）或RTX（10 nmol/L、100 nmol/L）处理10分钟。在培养3天时，与对照组相比，用CAP或RTX刺激10分钟后SP释放显著增加。急性暴露于CAP或RTX 6天后，与对照组相比，CAP和RTX处理的培养物中大鼠DRG神经元的SP释放和SP表达均显著降低。前速激肽原（PPT）mRNA、TRPV1 mRNA和TRPV1蛋白表达在CAP处理的培养物以及用较高浓度处理的RTX培养物中降低，而用较低浓度处理的RTX培养物则未受影响。结果表明，CAP和高浓度的RTX对培养的大鼠DRG神经元具有更强的神经毒性，而神经元在急性暴露于较低浓度的RTX后无法表达SP或TRPV1的情况在一段时间的孵育后可部分逆转。RTX可逆作用的功效和治疗潜力作为疼痛或神经源性炎症治疗策略更具适用性。
