ABSTRACT
Background@#The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. @*Methods@#Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 μg/kg) was injected for 10 days to develop neuropathic pain.The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. @*Results@#Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. @*Conclusions@#Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.
ABSTRACT
Background@#The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. @*Methods@#Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 μg/kg) was injected for 10 days to develop neuropathic pain.The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. @*Results@#Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. @*Conclusions@#Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.
ABSTRACT
Objective To discuss features of angiogenesis in degenerative intervertebral disc and related factors.Methods In this case-control study,52 patients undergoing single level posterior lumbar interbody fusion during October 2012 to December 2013 were selected as research objects.Annulus fibrosus,nucleus pulposus and cartilage end plate of responsible level were collected in surgery for frozen section and HE staining.Angiogenesis in the intervertebral disc was identified according to the morphological characteristics of vascular endothelial cells,i.e.typical lumen structure and blue stained nucleus.These intervertebral disc specimens were divided into two groups according to the angiogenesis phenomenon.All specimens with angiogenesis were evaluated by blood micro-vessel density (MVD) counting.Related factors of angiogenesis including gender,age,VAS score,JOA lumbar score,classification of lumbar intervertebral disc degeneration,intervertebral disc calcification rate and classification of intervertebral disc herniation were compared between the two groups.Logistic regression analysis was further conducted on indicators with differences of statistical significance.Results In our group of 52 patients,28 patients had obvious angiogenesis:12 patients in annulus fibrosus,7 patients in cartilage endplate and 9 patients in annulus fibrosus and nucleus pulposus.Angiogenesis rate was 53.8％ (28/52).The mean value of MVD was 12.5±3.1.24 patients did not have obvious angiogenesis.Intervertebral disc calcification rate (75.0％ vs.37.5％),VAS score (6.79±2.06 vs.5.25±2.23) and JOA lumbar score (16.32±3.89 vs.19.08±4.24) were significant differences between two groups (P=0.006,0.013,0.018).Multi-factor regression analysis showed that VAS score (OR=7.248,P=0.011) and intervertebral disc calcification (OR=8.881,P=0.006) were important factors associated with intervertebral disc angiogenesis.JOA lumbar score (OR=3.739,P=0.070) was not associated with intervertebral disc angiogenesis.Conclusion Degeneration of the intervertebral disc is accompanied by angiogenesis.Intervertebral disc calcification and VAS score are important factors associated with angiogenesis in intervertebral disc.
ABSTRACT
Objective To investigate the effect of peroxisome proliferator-activated receptor α agonist Wy14643 on mechanical ventilation-induced lung injury in rats.Methods Thirty-two healthy male SD weighing 250-300 g were randomly divided into 4 groups(n = 8 each): group Ⅰ control(group C);group Ⅱ mechanical ventilation(group V)and group Ⅲ,Ⅳ pretreated with different doses of Wy14643(group W1 ,W2).The animals were anesthetized with intraperitoneal 3% pentobarbital 30 mg/kg and tracheostomized.The femoral artery and external jugular vein were cannulated for blood sampling and drug administration.Group C received no mechanical ventilation.In group V,W1 and W2 the animals were mechanically ventilated for 2 h(VT 40 ml/kg,RR40 bpm,I:E=1:2,FiO2 21%).In group W1 and W2 Wy14643 1 and 3 mg/kg were administered iv at 1 h before mechanical ventilation.Arterial blood samples were collected at 1 and 2 h of mechanical ventilation for determination of PaO2/FiO2.Serum SOD activity and MDA concentration were measured at the end of 2 h mechanical ventilation.The animals were then killed and the lungs removed for microscopic examination,lung lavage and W/D lung weight ratio.The MIP-2 and TNF-α concentrations in BALF were measured.Results Two hour mechanical ventilation significantly decreased serum SOD activity and increased serum MDA concentration,W/D lung weight ratio and TNF-α and MIP-2 concentrations in BALF as compared with group C.Wy14643 pretreatment significantly attenuated these mechanical ventilation-induced changes in group W1 and W2 in a dose-dependent manner.Conclusion Wy14643 can attenuate mechanical ventilation induced lung injury in rats and it is related to the dose.