Mechanism of melatonin attenuating neuropathic pain through the SIRT1 BMAL1 pathway / 安徽医科大学学报

ABSTRACT

Objective @#To evaluate the effect of melatonin on nocturnal exacerbation of neuropathic pain and to ex plore its mechanism through the specific silencing information regulator 1 ( SIRT1)-brain and muscle ARNT-like protein 1 ( BMAL1 ) pathway .@*Methods @# 96 SPF grade male C57/B6 mice were randomly divided into three groups : the sham operation (S) group , the neuropathic pain model (NP) group and the NP model + melatonin treatment (10 mg/kg) ( NP + M) group; preoperative experimental mice were placed in the environment of the specified light pattern; the environment of alternating 12 h light and 12 h darkness was used for at least two weeks , and natural time was converted into the time of the award (ZT) , and the starting point of the light was ZT0; only the sciatic nerve was isolated in the S group , and the mouse NP model was prepared using chronic constriction injury (CCI) of the sciatic nerve in the NP group and the NP + M group , and the NP + M group was inj ected with me latonin after the operation; the expression levels of SIRT1, BMAL1, and glutathione peroxidase 1 (Gpx1) were de tected in the spinal cord at each time point at 14 d postoperatively by Western blot. Postoperative co-staining of SIRT1 in the dorsal horn of the spinal cord with the spinal cord neuronal marker neuron specific nuclear protein (NeuN) , the microglial cell activation marker ion calcium binding adapter molecule 1 (iba-1) , and the astrocyte marker glial fibrillary acidic protein ( GFAP) was carried out by immunofluorescence and iba-1 was detected at each time point to determine the activation status of microglia.@*Results @#SIRT1 , BMAL1 and Gpx1 decreased in NP group mice at 14 d ZT22 postoperatively compared to ZT10 time point in NP group ( P < 0.05) ; SIRT1 and BMAL1 were elevated in NP + M group at ZT14 time point compared to ZT14 time point in NP group (P < 0.05) , whereas Gpx1 was elevated at ZT18 time point (P < 0.05) . SIRT1 was co expressed in the dorsal horn of the spinal cord and in microglia. C ompared with ZT10 time point , microglia expression decreased in NP group mice at ZT22 time point 14 d after surgery (P < 0.05) ; compared with ZT10 time point , there was no statistically significant difference in microglia expression in NP + M group mice at ZT22 time point 14 d after surgery .@*Conclusion@#Melatonin attenuates nocturnal exacerbation of neuropathic pain by a mechanism that may be related to activation of microglia SIRT1-BMAL1 pathway protein expression .