The neuroprotective effect of sodium pyruvate on mouse hippocampal neural HT22 cells / 中国药理学通报

Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.

Advances in molecular mechanisms of meiotic arrest and luteinizing hormone-induced meiotic resumption in oocytes / 生理学报

Mammalian oocytes within Graafian follicles are arrested at prophase I of meiosis. C-type natriuretic peptide (NPPC), secreted by mural granulosa cells (MGCs), maintains oocyte meiotic arrest via binding to its cognate receptor natriuretic peptide receptor 2 (NPR2) and producing cyclic guanosine monophosphate (cGMP). NPR2 is most concentrated in the cumulus cells. In addition, cAMP, gap junction, inosine monophosphate dehydrogenase (IMPDH) and other important regulatory factors are also involved in meiotic arrest. Luteinizing hormone (LH) then rapidly decreases cGMP and induces oocyte meiotic resumption. In this paper, advances in the molecular mechanisms of meiotic arrest and LH-induced meiotic resumption were reviewed. This paper may provide new ideas for the prevention, diagnosis and treatment of related reproductive diseases.

The role of pinocembrin in t-PA thrombolysis-induced hemorrhagic transformation / 药学学报

Hemorrhagic transformation (HT) is a frequent complication of ischemic stroke, especially after thrombolytic therapy. This event is associated with increased morbidity and mortality. Tissue plasminogen activator (t-PA), the only FDA proved drug for breaking blood clots, is underutilized in ischemic stroke, because of its limited therapeutic window and hemorrhagic complications. Due to the lack of clear understanding of the pathological mechanism, there are no effective drugs to decrease the incidence of HT. Pinocembrin is a natural flavonoid compound and has neuroprotective effects in animal ischemic stroke models. In this study, we investigated the role of pinocembrin in t-PA thrombolysis-induced HT in rat thromboembolic stroke model. t-PA was administrated 6 h after ischemia and pinocembrin (5, 10 and 20 mg·kg-1) was given 5 min before t-PA administration. Infarct volume, neurological score and hemoglobin content were evaluated at 24 h after ischemia. Evans blue leakage was used to detect blood-brain barrier (BBB) permeability. All procedures were approved by the Institutional Animal Care and Use Committee of the Peking Union Medical College. The results showed that treatment with t-PA at 6 h after ischemia aggravated brain injury and increased the risk of HT, with infarct volume and brain water content reached 39% and 83.4%, respectively. Pretreatment with pinocembrin decreased the infarct volume and brain water content to 28.5% and 80.3%, and improved neurological function. In addition, the combined application of pinocembrin with t-PA reduced hemoglobin content and Evans blue content in brain tissue by 50% and 40%, indicating that pinocembrin could protect the BBB permeability and reduce the occurrence of HT. Among these doses, 10 mg·kg-1 is most effective. In conclusion, our results demonstrate that the combination of pinocembrin with t-PA protects against cerebral ischemia, reduces the occurrence of HT induced by t-PA thrombolysis. Thus, pinocembrin may be a potential therapeutic drug for t-PA induced HT.

Effects of caspases on cerebromicrovascular endothelial cell apoptosis induced by hypoxia / 药学学报

<p><b>AIM</b>To study the effects of caspases on cerebromicrovascular endothelial cell apoptosis induced by hypoxia in vitro.</p><p><b>METHODS</b>The cultured bovine cerebromicrovascular endothelial cells were exposed to NaCN in glucose-free medium. Cell viability was determined by trypan blue staining. Cell apoptosis was defined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and flow cytometry. The expression of caspase-3 was detected by immunocytochemical method. Four caspase inhibitors were used to validate the effect of caspases on cell apoptosis.</p><p><b>RESULTS</b>NaCN in glucose-free medium initiated cerebromicrovascular endothelial cell injury markedly and typical apoptotic cells were found in this model. The expression of caspase-3 increased significantly. Four caspase inhibitors decreased the number of injured cells. Selective inhibitor of caspase-1 and -6 reduced expression of caspase-3 significantly.</p><p><b>CONCLUSION</b>The results suggest that caspases family plays an important role in cerebromicrovascular endothelial cell apoptosis induced by NaCN and caspase-3 acts on the downstream of caspase-1 and -6 in protease cascade action to induce apoptosis.</p>

Protective effect of puerarin on vascular endothelial cell apoptosis induced by chemical hypoxia in vitro / 药学学报

<p><b>AIM</b>To study the effect of puerarin on vascular endothelial cells apoptosis induced by chemical hypoxia-ischemia in vitro.</p><p><b>METHODS</b>The chemical hypoxia-ischemia model was performed by treating cultured bovine aortic endothelial cells (BAECs) with NaCN in glucose-free medium. Cell viability was determined by trypan blue staining. Cell apoptosis was defined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), flow cytometry and Hoechst 33342 staining. The expression of Caspase-3 in endothelial cells was detected by immunocytochemical method.</p><p><b>RESULTS</b>Chemical hypoxia-ischemia was shown to initiate bovine aortic endothelial cell apoptosis. Puerarin (0.5-3 mmol.L-1) was found to inhibit endothelial cell apoptosis effectively, and reduce the expression of Caspase-3 significantly.</p><p><b>CONCLUSION</b>Puerarin can protect apoptotic endothelial cells induced by chemical hypoxia-ischemia markedly and the effect was performed partly by decreasing Caspase-3 expression.</p>