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.
ABSTRACT
To evaluate the prognostic value of glycated haemoglobin (HbA1c) in patients with acute myocardial infarction (AMI). Methods: A total of 1952 AMI patients were retrospectively studied. Based on medical history and HbA1c level, the patients were divided into 4 groups: Diabetes mellitus (DM) group, the patients with known DM or taking hypoglycemic drugs, n=492, Newly diagnosed DM group, MD was diagnosed during hospital stay and HbA1c≥6.5%, n=128, Pre-DM group, HbA1c 5.7%-6.4%, n=783 and Non-DM group, HbA1c<5.7%, n=549. The patients were followed-up for 25.6 months, prognostic differences during hospital stay and follow-up period were assessed by single- and multi-factor analysis. Results: The in-hospital mortality in DM group, Newly diagnosed DM group, Pre-DM group and Non-DM group were 4.88%, 3.91%, 3.96% and 2.91% respectively, P=0.435. As HbA1c level increasing, the incidences of all-cause mortality, non-fatal MI and re-hospitalization were elevating, while the differences among groups were similar. The incidences of major adverse cardiovascular events (MACE) in above 4 groups were 39.84%, 35.94%, 33.97% and 27.87% respectively, P=0.001. Compared with Non-DM group, MACE incidences in the other 3 groups were as OR=1.33, 95% CI 1.05-1.69, OR=1.45, 95% CI 0.97-2.18 and OR=1.71, 95% CI 1.32-2.22 respectively, Ptrend<0.001; with adjusted baseline parameters, Ptrend=0.008. Conclusion: In our research, MACE incidence was increasing upon HbA1c level elevating in AMI patients and it was not related to in-hospital death. HbA1c level should be screened in AMI patients, lifestyle and drug intervention could be used as necessity.