TRPV1在LPS引起的大鼠发热伴疼痛或痛觉过敏中的作用

摘要

To investigate initially the role of TRPV1 in systemic LPS-induced fever with hyperalgesia in rats and possible mechanism.Being pretreated with TRPV1 antagonist capsazepine (CPZ) by intracerebroventricular injection for 30 minutes,rats were intraperitoneally injected LPS to induce fever.The changes of body temperature (Tc) and withdrawal latency were observed by microcomputer thermometer and plantar test,respectively.Meanwhile,the expression of TRPV1mRNA in POA and L3-L5 DRG (dorsal root gangilin) of rats were monitored by RT-qPCR after 6 hours with intraperitoneal injection LPS.The results showed that compared with the Sham,Tc and the withdrawal latency were not changed notably in CPZ;Tc was increased in LPS and in CPZ+LPS;the withdrawal latency was shortened in LPS group and lengthened in CPZ+LPS significantly.Compared with LPS,the altitude and the duration of fever induced by LPS were increased and the withdrawal latency was lengthened after blocking TRPV1 channel with CPZ in CPZ+LPS.The expression of TRPV1 mRNA was increased in POAH and in DRG in LPS,and increased in DRG but not changed significantly in POAH in CPZ + LPS vs Sham or CPZ.The results mentioned above suggest that TRPV1 might be activated during fever induced by LPS,while the altitude and the duration of fever was increased and pain sensitivity was decreased through blocking TRPV1 with CPZ.It is inferred that TRPV1 might negatively regulate core temperature of fever in rats and involves in generation of fever with hyperalgesia not only in the central nervous system but also in peripheral nervous system.%为探讨TRPV1在LPS引起的大鼠发热伴疼痛或痛觉过敏中的作用.采用经大鼠侧脑室给予TRPV1受体阻断剂辣椒平(Capsazepine,CPZ)、30 min后腹腔给予LPS诱导发热模型的方法.通过微电脑测温仪和足底疼痛测试仪间断观察大鼠体温(Tc)及痛觉潜伏期的变化;实时荧光定量PCR (RT-qPCR)检测给予LPS 6h大鼠POA和L3-L5段DRG部位TRPV1mRNA表达变化.结果显示:与对照组相比,CPZ组Tc和痛觉潜伏期无明显变化;LPS组Tc明显升高,潜伏期明显缩短;CPZ+LPS组Tc显著升高,但潜伏期明显延长.与LPS相比,CPZ+LPS组Tc升高显著,持续时间更久,潜伏期延长更加明显.相比Control组和CPZ组,LPS组POA和DRG部位TRPV1mRNA相对表达量均显著增加,CPZ+LPS组TRPV1mRNA相对表达量在POA部位无明显变化,在DRG部位显著增加.由此可知,正常体温状态下,TRPV1未参与大鼠体温及痛觉过敏的调节;通过阻断TRPV1使发热大鼠体温进一步升高,发热时程延长,痛觉潜伏期延长,表明发热时TRPV1被激活,对LPS诱导的发热具有一定的负调控作用,同时提高了痛觉敏感性;TRPV1可能在外周和中枢共同参与了体温调节和痛觉调制.