羟考酮对老年大鼠脊柱手术模型的镇痛及神经功能保护作用OA

Objective To investigate the analgesic and neuroprotective effects of oxycodone on senile spinal surgery model rats and its mechanism of action.Methods Surgical resection was used to replicate the senile spinal surgery rat model.40 successfully modeled rats were randomly divided into the model group(equal volume of normal saline),low-,medium-,and high-dose oxycodone groups(0.05,0.10,0.15 mg/kg),sufentanil group(1.5 μg/kg),with eight rats in each group.Another eight rats receiving the same anesthesia,disinfection,and incision treatment were used as the sham-operated group(equal volume of normal saline).The corresponding drugs or normal saline were injected via the tail vein once daily for 14 d.The analgesic effect was evaluated using spontaneous pain behavior score;the sedative effect was evaluated using Ramsay sedation score;mechanical pain threshold and thermal pain threshold were used to assess the sensitization of mechanical and thermal pain;heart rate variability(HRV)was measured by frequency domain method;enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of neurotransmitters[5-hydroxytryptamine(5-HT),substance P(SP)],stress indicators[adrenocorticotropic hormone(ACTH),cortisol(Cor),aldosterone(ALD)],inflammatory factors[C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin 6(IL-6)],and oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)];Western blot method was used to determine the protein expression levels of B-cell lymphoma-2(Bcl-2),protein kinase R-like endoplasmic reticulum kinase(PERK),and eukaryotic translation initiation factor 2α(eIF2α)in spinal dorsal horn tissue and spinal tissue.Results Compared with the model group,the spontaneous pain behavior scores at 2,6,12,24,and 48 h after the last administration in the sufentanil group and the medium-and high-dose oxycodone groups were significantly decreased,while Ramsay sedation scores,mechanical pain thresholds,and thermal pain thresholds were significantly increased(P<0.05);the HRV values were significantly increased(P<0.05);serum levels of 5-HT,SP,ACTH,Cor,ALD,CRP,TNF-α,IL-6,and MDA were significantly decreased,while serum levels of SOD and CAT were significantly increased(P<0.05);the protein expression levels of PERK and eIF2α in spinal dorsal horn tissue and spinal tissue were significantly decreased,and Bcl-2 protein expression level was significantly increased(P<0.05).Conclusion Oxycodone can exert analgesic effects and protect neurological function on senile rats after spinal surgery by regulating the PERK/eIF2α signaling pathway.