Mechanism Study of Endothelial Protection and Inhibits Platelet Activation of Low Molecular Weight Fucoidan from Laminaria japonica

Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline(0.4 mg kg-1) and human umbilical vein endothelial cells were cultured. v WF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce v WF level in vascular endothelial injury rats and also significantly reduce v WF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and v WF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

CYP2C8-derived Epoxyeicosatrienoic Acids Decrease Oxidative Stress-induced Endothelial Apoptosis in Development of Atherosclerosis:Role of Nrf2 Activation

The aim of the present study is to investigate how cytochrome P450 enzymes（CYP） 2C8-derived epoxyeicosatrienoic acids（EETs） regulate the nuclear factor erythroid 2-related factor 2（Nrf2） signaling pathway and protect against oxidative stress-induced endothelial injuries in the development and progression of atherosclerosis. In this study,cultured human umbilical vein endothelial cells（HUVECs） were transfected with CYP2C8 or pretreated with exogenous EETs（1 μmol/L） before TNF-α（20 ng/m L） stimulation. Apoptosis and intracellular ROS production were determined by flow cytometry. The expression levels of ROS-associated NAD（P）H subunits gp91 and p47,the anti-oxidative enzyme catalase（CAT）,Nrf2,heme oxygenase-1（HO-1） and endothelial nitric oxide synthase（e NOS） were detected by Western blotting. The results showed that CYP2C8-derived EETs decreased apoptosis of HUVECs treated with TNF-α. Pretreatment with 11,12-EET also significantly blocked TNF-α-induced ROS production. In addition,11,12-EET decreased oxidative stress-induced apoptosis. Furthermore,the ability of 11,12-EET to protect cells against TNF-α-induced apoptosis via oxidative stress was abrogated by transient transfection with Nrf2-specific small interfering RNA（si RNA）. In conclusion,CYP2C8-derived EETs prevented TNF-α-induced HUVECs apoptosis via inhibition of oxidative stress associated with the Nrf2 signaling.

Protective Effect of 10-Hz,1-mT Electromagnetic Field Exposure Against Hypoxia/Reoxygenation Injury in HK-2 Cells

We investigated the protective effects of electromagnetic field（EMF）on the survival of the human renal proximal tubular cell line,HK-2,using an in vitro hypoxia/reoxygenation（H/R）injury model.The survival rate of cells cultured under H/R condition declined significantly,while the intracellular reactive oxygen species（ROS）levels markedly increased.The 10 Hz/1 m T EMF exposure could inhibit H/R-induced cell death of HK-Z via suppression of intracellular ROS production and that this treatment might be clinically useful for the amelioration of renal ischemia/reperfusion injury.