ABSTRACT
Objective: To investigate the protective effect of sodium ferulate on cerebral ischemia-reperfusion injury in rats and to explore its possible mechanism.Method: The cerebral ischemia reperfusion injury model was established by middle cerebral artery occlusion (MCAO) in SD male rats. 36 modeled rats with neurologic damage were randomly divided into 4 groups:model group, low,medium,high-dose sodium ferulate groups (25,50,100 mg·kg-1).Another nine rats were selected as a sham operation group.Neurological function was assessed by neurological scoring system in rats.Hematoxylin-eosin (HE) staining was performed to observe the pathological changes of the rats' brain. The levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in serum and brain tissues were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein expression of nucleus and cytoplasm nuclear factor-kappa B p65 (NF-κB p65) in brain tissues.Result: As compared with normal group, neurological deficit score was increased; the neuronal necrosis and inflammatory cell number were present;the serum and brain tissue levels of TNF-α, IL-1β and IL-6 were increased; nucleus/cytoplasm NF-κB p65 protein expression ratio was increased significantly in model group (PPPα, IL-1β and IL-6(PPκB p65 protein(PPConclusion: Sodium ferulate protects the brain against focal cerebral ischemia reperfusion injury, and the mechanism may be related to inhibiting nuclear translocation of NF-κB p65 protein to alleviate inflammatory response.
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AIM:To investigate the effect of toosendanin(TSN)on invasion and migration abilities of human ovarian cancer cells and the related mechanism.METHODS:The human ovarian cancer cell lines CAVO-3 and SKVO-3 were treated with TSN at different concentrations.The cell viabilty at 12,24,48,72 and 96 h after TSN treatment was measured by CCK-8 assay.Scratch wound healing assay and Transwell assay were employed to measure the invasion and migration abilities of CAVO-3 cells.The protein expression of nuclear factor-κB(NF-κB)p65,E-cadherin,N-cadherin,vimentin and Snail was determined by Western blot.RESULTS:TSN significantly inhibited the viability of CAVO-3 and SKVO-3 cells(P<0.05 ).Compared with control group ,the migration and invasion abilities of CAVO-3 cells in TSN group decreased significantly(P<0.05).In addition,the expression of NF-κB p65 and E-cadherin protein increased no-tably,followed with N-cadherin,vimentin and Snail protein decreased significantly(P<0.05).However,the inhibitor of NF-κB BAY11-7082 reversed the impact above.Compared with TSN group ,the migration and invasion abilities in TSN +BAY11-7082 group increased significantly(P<0.05).The protein expression of E-cadherin also decreased notably ,fol-lowed with the protein expression of N-cadherin,vimentin and Snail increased significantly(P<0.05).CONCLUSION:TSN inhibits the invasion and migration abilities of human ovarian cancer cells ,which is related to the inhibition of epitheli-al-mesenchymal transition process mediated by NF-κB/Snail signaling pathway.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism of the protective effects of Panax notoginseng saponins (PNS) on kidney in diabetic rats.</p><p><b>METHODS</b>Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg day) and PNS-200 mg/(kg day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7 (BMP-7). Silent information regulator 1 (SIRT1) was silenced in rat mesangial cells by RNA interference. The mRNA expressions of SIRT-1, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB (NF-κB) P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde (MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase (SOD) was detected by the classical method of nitrogen and blue four.</p><p><b>RESULTS</b>In diabetic model rats, PNS could not only reduce blood glucose and lipid (P<0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1 (P<0.01) and in turn suppress the transcription of TGF-β1 (P<0.05) and MCP-1 (P<0.05). PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated (P<0.05) and SOD was up-regulated (P<0.01), which were both induced by SIRT1 up-regulation.</p><p><b>CONCLUSIONS</b>PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins.</p>
Subject(s)
Animals , Male , Acetylation , Antioxidants , Metabolism , Blood Glucose , Metabolism , Bone Morphogenetic Protein 7 , Metabolism , Chemokine CCL2 , Metabolism , Diabetes Mellitus, Experimental , Blood , Drug Therapy , Genetics , Gene Knockdown Techniques , Immunohistochemistry , Kidney , Pathology , Kidney Function Tests , Lipids , Blood , Malondialdehyde , Metabolism , Mesangial Cells , Metabolism , Oxidative Stress , Panax notoginseng , Chemistry , Plasminogen Activator Inhibitor 1 , Genetics , Metabolism , Protective Agents , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , Saponins , Pharmacology , Therapeutic Uses , Sirtuin 1 , Genetics , Superoxide Dismutase , Metabolism , Transcription Factor RelA , Metabolism , Transcription, Genetic , Transforming Growth Factor beta1 , Metabolism , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To compare the effects of mannitol and hypertonic saline (HS) in treatment of intracranial hypertension (ICH) of rabbits.</p><p><b>METHODS</b>The animal mode of ICH was established by perfusing artificial cerebrospinal fluids (aCSF) with controlled pressure into the cerebral ventricles of rabbits. The mean arterial pressure, respiratory rate, tidal volume, perfusion rate of aCSF and water content of cerebrum were investigated in rabbits with ICH after a single bolus of 20% mannitol (5 ml/kg), 7.5% HS (2.2 ml/kg) or 23.4% HS (2.2 ml/kg).</p><p><b>RESULTS</b>After the intracranial pressure was elevated from 15 cmH₂O to 75 cmH₂O, the mean arterial pressure was increased and the tidal volume was decreased. After treatment by 20% mannitol, 7.5% HS or 23.4% HS, the increased percentage of mean arterial pressure and the decreased percentage of tidal volume were similar to the changes in control group. However, the perfusion rate of CSF was increased and water content of cerebrum was decreased after treatment by either 20% mannitol or 23.4% HS, but not by 7.5% HS. No different effects were found between 20% mannitol and 23.4% HS.</p><p><b>CONCLUSION</b>With the similar osmotic burden, 20% mannitol is more effective in treating ICH than 7.5% HS. With higher osmotic load, the efficacy of HS is enhanced, and 23.4% HS may be used as an alternative to mannitol in treatment of ICH.</p>