Effect of exchange protein directly activated by cyclic adenosine monophosphate 1 on mechanical pain of diabetic rats / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate effect of exchange protein directly activated by cyclic adenosine monophosphate 1 on mechanical pain in diabetic rats.Methods Male SD rats were randomly divided into CON group and STZ group. CON group were further randomly divided into CONshRNA group,and CONEpac1shRNA group. STZ group induced diabetic mechanical pain (DMA) model were randomly divided into DMA shRNA group, DMA Epac1shRNA group,DMANS group,and DMA 8-pCPT group. The Epac1shRNA lentivirus vector is used to inhibit the expression of Epac1, and the shRNA lentivirus vector is negative control, and 8-pCPT is the activator of Epac1. Group CONshRNA and group DMAshRNA were given intrathecal injection of control shRNA lentivirus vector. Group CONEpac1shRNA and group DMAEpac1shRNA were injected with Epac1shRNA lentivirus carrier, DMANS group was injected into the plantar saline,and 8-pCPT in group DMA8-pCPT was injected into the foot. The changes of hind paw retraction threshold(PWT) were observed and the expression of guanine nucleotide transforming factor 1(Epac1) mRNA was detected by Real Time-PCR and Western blot in rat dorsal root ganglion(DRG) And protein expression changes.Results Compared with CON rats,the mechanical pain threshold of STZ rats decreased (P=0.035). Compared with saline group,the pain of injection Epac1 activator 8-pCPT group was prolonged(2h, P=0.012;4h,P=0.020). The expression of Epac1 mRNA and protein was significantly higher in the DMA group than in the CON group(both P<0.01). Intrathecal injection of shRNA reduced the expression of Epac1 mRNA and protein(P<0.01,P=0.020),and the PWT of the DMA group was significantly lower than that of the CON group (P=0.006).Conclusion Epac1 expression in diabetic rats with increased pain,and down-regulation of Epac1 may relieve pain.