ABSTRACT
Sodium tanshinone IIA sulfonate (STS) has shown significant clinical therapeutic effects in cerebral ischemic stroke (CIS), but the molecular mechanisms of neuroprotection remain partially known. The purpose of this study was to explore whether STS plays a protective role in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by regulating microglia autophagy and inflammatory activity. Co-cultured microglia and neurons were subjected to OGD/R injury, an in vitro model of ischemia/reperfusion (I/R) injury with or without STS treatment. Expression of protein phosphatase 2 A (PP2A) and autophagy-associated proteins Beclin 1, autophagy related 5 (ATG5), and p62 in microglia was determined by Western blotting. Autophagic flux in microglia was observed with confocal laser scanning microscopy. Neuronal apoptosis was measured by flow cytometric and TUNEL assays. Neuronal mitochondrial function was determined via assessments of reactive oxygen species generation and mitochondrial membrane potential integrity. STS treatment markedly induced PP2A expression in microglia. Forced overexpression of PP2A increased levels of Beclin 1 and ATG5, decreased the p62 protein level, and induced autophagic flux. Silencing of PP2A or administration of 3-methyladenine inhibited autophagy and decreased the production of anti-inflammatory factors (IL-10, TGF-ß and BDNF) and induced the release of proinflammatory cytokines (IL-1ß, IL-2 and TNF-α) by STS-treated microglia, thereby inducing mitochondrial dysfunction and apoptosis of STS-treated neurons. STS exerts protection against neuron injury, and the PP2A gene plays a crucial role in improving mitochondrial function and inhibiting neuronal apoptosis by regulating autophagy and inflammation in microglia.
Subject(s)
Reperfusion Injury , Stroke , Humans , Oxygen/metabolism , Signal Transduction , Glucose/metabolism , Beclin-1/metabolism , Autophagy , Apoptosis , Stroke/metabolism , Neurons/metabolism , Mitochondria/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/prevention & control , Reperfusion Injury/metabolismABSTRACT
Objective To evaluate the clinical efficacy of sodium tanshinone IIA sulfonate(STS)in the treatment of ad-vanced schistosomiasis. Methods Fifty cases with advanced schistosomiasis admitted to the Touzao Township Hospital of Dong-tai City during the period from November 2012 to November 2013 were treated with STS for 10 days,and the internal diameter of the portal vein,levels of ALT,AST,γ-GT,PIIIP,CIV,HA and LN were measured and compared before and after the adminis-tration of STS. Results The mean levels of all serological parameters except HA were within the normal range before STS treat-ment,while the highest positive rate was detected inγ-GT(26.0%)and HA(54.0%). Following the STS treatment,the mean lev-els of all parameters and the positive rates reduced,with the greatest reduction observed inγ-GT(36.7%)and HA(37.8%);how-ever,the mean HA level was still higher than the normal range. The mean internal diameter of the portal vein reduced from(10.5± 1.7)mm before the STS treatment to(9.8±1.3)mm after the STS administration,with a significant diffrtence(P<0.05). Conclu-sion STS appears effective in the treatment of advanced schistosomiasis.
