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 inju-ry(CCI)of the sciatic nerve in the NP group and the NP+M group,and the NP+M group was injected 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 spi-nal cord and in microglia.Compared 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 signifi-cant 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.
万方数据
维普
