Role of spinal peroxisome proliferation-activated receptor-γ in protection D1-induced reduction of neuropathic pain in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of spinal peroxisome proliferation-activated receptor-γ (PPAR-γ) in protectin D1 (PD1)-induced reduction of neuropathic pain (NP) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (Sham group), NP group, NP plus PD1 group (NP+ PD group), and NP plus PD1 plus GW9662 group (NP+ PD+ GW group). Neuropathic pain was induced by spared nerve injury in anesthetized rats.In NP+ PD and NP+ PD+ GW groups, PD1 900 ng (diluted to 20 μl in dimethyl sulfoxide [DMSO]) was intrathecally injected once a day for 8 consecutive days starting from 30 min before establishing the model.In NP+ PD+ GW group, the PPAR-γ antagonist GW9662 200 ng (diluted to 20 μl in DMSO) was intrathecally injected once a day for 8 consecutive days starting from 45 min before establishing the model.The equal volume of DMSO was intrathecally injected in Sham group.The mechanical paw withdrawal threshold (PWT) was measured before establishing the model and at 1, 3, 5, 7, 10 and 14 days after establishing the model.Six rats in each group were sacrificed on day 14 after establishing the model, and their lumbar enlargements were removed for determination of the expression of PPAR-γ, TNF-α and IL-6 by Weston blot.Six rats in each group were sacrificed on day 14 after establishing the model, L 4, 5 segments of the spinal cord were removed, and the co-expression of PPAR-γ with neuron-specific nucleoprotein (NeuN), glial fibrillary acidic protein (GFAP) or serum calcium binding adapter molecule 1 (Iba-1) was determined by immunofluorescence staining. Results:Compared with group Sham, PWT was significantly decreased at each time point after establishing the model, the expression of PPAR-γ was down-regulated, and the expression of TNF-α and IL-6 was up-regulated in the other three groups ( P<0.05). Compared with group NP, PWT was significantly increased at 7-14 days after establishing the model, the expression of PPAR-γ was up-regulated, and the expression of TNF-α and IL-6 was down-regulated in group NP+ PD, and no significant change was found in the parameters mentioned above in group NP+ PD+ GW ( P>0.05). Compared with group NP+ PD, PWT was significantly decreased at 7-14 days after establishing the model, the expression of PPAR-γ was down-regulated, and the expression of TNF-α and IL-6 was up-regulated in group NP+ PD+ GW ( P<0.05). The results of immunofluorescence staining of the spinal cord showed that PPAR-γ was co-expressed with NeuN and GFAP. Conclusion:The mechanism by which PD1 mitigates NP is related to promoting the activation of PPAR-γ in spinal cord neurons and astrocytes and inhibiting inflammatory responses in rats.