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Objective Glucagon-like peptide-1 (GLP-1) has been reported to be effective in the treatment of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanism of GLP-1 on NAFLD is remained unclear. The present study was to detect whether the effect of GLP-1 on triglyceride (TG) content in hepatocytes is dependent on Foxos. Methods HepG2 cells were treated with palmitic/oleic acid for 24 h. The knockdown of Foxo1, Foxo3 was conducted through small interfering RNA (siRNA). Real time PCT (RT-PCR) was used to detect the changes of the SREBP1c and Acox2 genes in HepG2 cells after Foxo1/3 knockdown. Results As expected, palmitic/oleic acid increased TG concentration in HepG2 cells [(12.65 ± 1.32) μg/mg vs. (4.32 ± 0.54) μg/mg, P<0.05]. Addition of GLP-1 dose (10, 50, 100nmol/L) dependently lowered the TG content and reached plateau at 100 nmol/L of GLP-1 [TG(8.38±1.47) μg/mg]. The GLP-1 effect on TG remained after knocking down either Foxo1 [(9.09±1.34)μg/mg] or Foxo3 [(8.90± 1.60) μg/mg] alone, but not when knocking down Foxo1 and Foxo3 (Foxo1/3) together [(14.66±1.77)μg/mg]. Moreover, knocking down Foxo1/3 also abolished GLP-1 effect on SREBP1c and Acox2 expression. Conclusion GLP-1 can inhibit the synthesis of TG in hepatocytes depending on Foxo1 and Foxo3. Further studies are needed to explore the specific mechanisms.
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Objective To explore the effect of resolvin D2 ( RvD2) on radicular pain induced by interver-tebral disc herniation. Methods Thirty-six male Sprague-Dawley rats were randomly divided into a sham opera-tion group, a model group and an RvD2 group, each of 12. Non-compressive lumbar disc herniation was induced in the rats in the model and RvD2 groups using the autologous nucleus pulposus filling method. Those in the sham group had the surgical site exposed without any other treatment. After the modeling, 10μl of phosphate-buffered sa-line solution was administered intrathecally to the rats in the sham and model groups for 3 days, while the rats in the RvD2 group received 10 ng/10 μl of RvD2 intrathecally as well. Paw withdrawal thresholds (50％PWT) were ob-served 1 day before modeling and 7 days afterward for the rats of all three groups. On the 7th day after modeling, the L4 to L6 spinal dorsal horns on the surgery side were resected to detect the protein expression of phosphorylated protein kinase B ( p-AKT) , protein kinase B ( t-AKT) , phosphorylated glycogen synthase kinase 3β( p-GSK-3β) and glycogen synthase kinase 3β( GSK-3β) using western blotting. The protein levels of tumor necrosis factor alpha ( TNF-α) , interleukin-6 ( IL-6) , transforming growth factor-β1 ( TGF-β1) and interleukin-10 ( IL-10) were de-termined using enzyme-linked immunosorbent assays. Results On the 1st and 7th day after modeling, significant differences were observed between the model and sham groups in terms of the 50％PWT. From the 3rd day the aver-age 50％PWT in the RvD2 group was significantly higher than that of the model group at the same time points. On the 7th day after the modeling the average p-AKT and p-GSK-3βprotein levels of the model and RvD2 groups were significantly different from that of the sham group, and the model group′s average was also of significantly different from that of the RvD2 group. The average protein levels of the pro-inflammatory cytokines TNF-αand IL-6, as well as of the anti-inflammatory factors TGF-β1 and IL-10 in the dorsal horns of the model group and the RvD2 group were also significantly different on the 7th day, and both were significantly different from the sham group′s average. Conclusion RvD2 can alleviate radicular pain in rats with non-compressive disc herniation. The mechanisms might involve inhibition of GSK-3β activity, down-regulation of pro-inflammatory factors and up-regulation of anti-inflammatory factors.
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Objective To evaluate the effect of exogenous resolvin D2 on radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 230-270 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),radicular pain induced by non-compressive lumbar intervertebral disc herniation group (group P) and exogenous resolvin D2 group (group R).The right L5 dorsal root ganglions were covered by autologous nucleus pulposus tissues to establish the model of non-compressive lumbar disc herniation in P and R groups.The corresponding surgical site was only exposed in group S.The corresponding drugs were intrathecally injected within 3 days after establishing the model,phosphate buffer solution 10 μl was injected in group P,1 ng/μl resolvin D2 solution 10 μl was injected in group R,and normal saline 10 μl was given for pipe washing after administration in the three groups.The mechanical paw withdrawal threshold (MWT) was measured on 1 day before establishing the model and 1-7 days after establishing the model.The spinal dorsal horns of lumbar enlargement segments were removed on day 7 after establishing the model for determination of the expression of glial fibrillary acidic protein (GFAP) (by Western blot) and co-expression of G-protein-coupled receptor 18 with GFAP (by double-label immunofluorescence).Results Compared with group S,the MWT was significantly decreased at 1-7 days after establishing the model,and the expression of GFAP was up-regulated in group P (P＜0.05).Compared with group P,the MWT was significantly increased at 3-7 days after establishing the model,and the expression of GFAP was down-regulated in group R (P＜0.05).G-protein-coupled receptor 18 was co-expressed with GFAP.Conclusion Exogenous resolvin D2 can reduce radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation,and the mechanism is related to inhibiting activation of astrocytes in the spinal dorsal horns.