Acute cerebral ischemia-induced down-regulation of Sirt3 protein expression contributes to neuronal injury via damaging mitochondrial function / 生理学报

This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 overexpression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel strategy against neural injuries caused by acute cerebral ischemia.

Effect of paeoniflorin on irritable bowel syndrome and barrier function of intestinal epithelia cell / 国际药学研究杂志

Objectives To investigate the effect of paeoniflorin(PF)in ameliorating the irritable bowel syndrome(IBS)such as diarrhea and bellyache,and the barrier function of PF on intestinal epithelial cell and inflammation.Methods The diarrhea model was conducted by exposing rat to restraint stress stimulation and bellyache model was conducted by subcutaneous injection of neostig?mine to mice.The Caco-2 monolayer cell model with barrier dysfunction was established by trypsin stimulation and the inflammatory Caco-2 cell model was established by interleukin-1β(IL-1β)stimulation.On the basis of these models,effects of PF at different doses (low 14 mg/kg·d,medium 28 mg/kg·d,and high 56 mg/kg·d)on IBS syndromes and Caco-2 cell function were investigated. Re-sults PF could significantly reduce the frequency of defecation in diarrhea rat model(P<0.05)and relieve abnormal bowel move?ments in bellyache mice model(P<0.05).PF significantly increased TEER value(P<0.01),decreased the transmittance of fluores?cein(P<0.01)and up-regulated the expression of tight junction(ZO-1)protein(P<0.01).The gene and protein expression of nucle?ar factor profilin kappa Bα(IκBα)in inflammatory Caco-2 cell model was significantly improved(P<0.01)when treated with PF. Conclusion Our study proves for the first time that PF significantly ameliorated the diarrhea and bellyache symptoms of IBS in the di?arrhea model and bellyache model.The PF intervention effect on ZO-1 and IκBα protein might be one of the molecular mechanism of ameliorating the symptoms of IBS.