Background:Type Ⅱ diabetes mellitus（DM） is thought to be a risk factor for thromboembolism（VTE）.Elevated plasma levels of plasminogen activator inhibitor-1（PAI-1） are associated with ***,the role of PAI-1 in th...
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Background:Type Ⅱ diabetes mellitus（DM） is thought to be a risk factor for thromboembolism（VTE）.Elevated plasma levels of plasminogen activator inhibitor-1（PAI-1） are associated with ***,the role of PAI-1 in the development of DM-associated VTE is poorly ***:Our aim was to determine the role of PAI-1 in the DM-associated VTE,and to test the hypothesis that inhibiting PAI-1 promotes venous thrombosis ***:Thrombosis was induced in the inferior vena cava（IVC） and saphenous vein of *** mellitus was induced by feeding mice high fat diet（DM group）.PAI-039,a specific,small molecule pharmacological inhibitor of PAI-1,was orally administered to mice（2mg/kg twice daily）.The gene expression of PAI-1,MMP-2,9,MT1-MMP,and VEGF in thrombus were assessed by real-time ***:Thrombus size and collagen content were substantially larger at 3 days after IVC ligation in DM mice compared to NC mice（p<0.05）.Intrathrombotic PAI-1,MMP-2,MMP-9,MT1-MMP,and VEGF gene expression were significantly enhanced in DM mice compared to WT mice（p<0.01）.We also subjected DM and NC mice to FeCl saphenous vein injury and measured the time required to form an occlusive *** mean time to occlusion in DM mice（322±27seconds,n=6）was significantly shorter than that in NC mice（473 ± 66 seconds,n=6,p<0.05）.The inhibition of PAI-1 by PAI-039 reduced thrombus size in IVC ligation model（p<0.05）and delayed vein occlusion time（p<0.001） compared with vehicle-treated *** expression of intrathrombotic MMP-9,MT1-MMP,and VEGF,but not MMP-2was markedly increased by the treatment of PAI-039 compared with vehicle ***:Taken together,these findings show that pharmacologic inhibition of elevated PAI-1 rescues the impairment in thrombus resolution observed in DM,and may have efficacy as a therapeutic strategy to prevent diabetic *** of Interest:None Declared
The immune dysfunction is involved in the uncontrolled inflammation following hemorrhagic shock,which is associated with post-hemorrhagic shock mesenteric lymph（PHSML） *** study was conducted to investigate the effe...
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The immune dysfunction is involved in the uncontrolled inflammation following hemorrhagic shock,which is associated with post-hemorrhagic shock mesenteric lymph（PHSML） *** study was conducted to investigate the effect of PHSML on CD4 T lymphocytes,in vivo and in ***,we established the model of hemorrhagic shock[（40±2） mmHg for 60 min,follow by fluid resuscitation],and observed the role of PHSML drainage on the CD4 T lymphocytes isolated from the spleen in ***,we drained the normal mesenteric lymph（NML）,PHSML during hypotension（PHSML-H）,and PHSML from 0 h to 3 h after resuscitation（PHSML-R）,for the incubation with the CD4 T lymphocytes obtained from normal *** results showed that hemorrhagic shock decreased the proliferation of CD4T lymphocytes to ConA,the IL-2 and IL-2 receptor（IL-2R） mRNA expressions,the phenotype of IL-2R on the surface of CD4 T lymphocytes,the IL-2,DFN-γ levels in supernatants,along with an increase in IL-4 level,which were reversed by PHSML ***,in vitro,NML incubation promoted CD4 T lymphocytes proliferation,along with enhancement at early stage and inhibition at later stage induced by PHSML-H and PHSML-R treatment,***,NML induced an increased trend in the IL-2 and IFN-γ,and decreased trend in the IL-4 with prolonged stimulation;PHSML-H induced increases in IL-2 at 12 h and IL-4 at 24 h,decreases in IL-2 and IFN-γ at 24 h,IL-4 at 12 h;PHSML-R induced increases in IL-2,IL-4,and IFN-γ at 24 h,a decrease in IL-4 at 12 ***,the levels of IL-2,IL-4,and IFN-γ at 24 h in the PHSML-R treatment were decreased than that of the PHSML-H *** results indicated that PHSML was involved in the process of uncontrolled inflammatory response caused by cell immune dysfunction following hemorrhagic shock.
Objective:To investigate the TLR4(Toll like receptor 4)-TRAF6(tumor necrosis factor receptor associated-factor 6) signal pathway expression in rats intestinal ischemia and reperfusion(IR) injury,as well as the express...
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Objective:To investigate the TLR4(Toll like receptor 4)-TRAF6(tumor necrosis factor receptor associated-factor 6) signal pathway expression in rats intestinal ischemia and reperfusion(IR) injury,as well as the expression and significance after ischemic preconditioning(IP) in rat intestine and distant organs of TRAF6 and SOCS-1(Suppressor of cytokine signaling-1).Methods:48 Sprague-Dawley(SD) male rats(250-300g) were randomized(n = 8),sham group,rats received the dissection of superior mesenteric artery(SMA),then the abdomen was closed for 2h;further divided into 1h、 3h、 6h ischemia group,using noninvasive vascular clamp to clamping SMA and creatting intestinal ischemia model;IR group,clamping SMA for 1h and 1h reperfusion 1h;IP group,rats underwent 10 minutes ischemia and 10 minutes reperfusion,then clamping SMA for 1h and 1h reperfusion *** animals executed immediately and collecting *** histologic injury was observed,TUNEL(TdT-mediated dUTP Nick-End Labeling) staining to detect apoptotic cells,TRAF6 and SOCS-1 expression was detected by immunehistochemistry in the intestine tissue,real-time quantitative PCR(Real-time quantitative PCR)、 Western blot to detect TLR4,TRAF6,RIP(receptor interacting protein),Caspase-3(cysteinyl aspartate specific proteinase-3),SOCS 1 expression in the intestine and distant organs ***:Compared with IR,IP reduced the apoptosis cell in rat intestinal(2.42±0.10 VS 10.04±0.24,p <0.05);IP significantly inhibited the MPO(Myeloperoxidase) activity(32.49±1.56U/ LVS65.89±1.61U/L,p <0.05);quantitative PCR detect the expression of intestinal TRAF6 mRNA after IP which reduced(1.20±0.04VS2.10±0.11,p <0.05),while SOCS-1mRNA upregulation(1.93±0.15VS0.48±0.19,P<0.05);IP also significantly reduced TRAF6(0.83±0.12VS2.36±0.23,p <0.05) while increased SOCS-1(1.00±0.16VS0.66±0.08,p <0.05) protein expression in intestinal tissues;in addition,after intestinal ischemia and reperfusion injury as well as IP,there are similar cha
Coagulation factor V(fV) is distributed in plasma and platelet pools distinguished by physical and functional *** has been extensively studied for its roles in *** roles of fV in other physiological pathways remain **...
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Coagulation factor V(fV) is distributed in plasma and platelet pools distinguished by physical and functional *** has been extensively studied for its roles in *** roles of fV in other physiological pathways remain ***:In the current study,we report that platelet fV is critical for the regulation of angiogenesis in a mouse model of hind-limb *** ischemia was produced in mice by femoral artery ligation in transgenic mice,with different level of fV gene expression restricted to either the plasma or *** hindlimb blood flow perfusion in mice with higher platelet fV was significantly ***,using a platelet depletion/transfusion procedure,transfusion of platelets with higher level of fV into transgenic mice with undetectable platelet fV significantly rescued the ischemia-mediated impairments in blood flow *** analysis also indicated markedly increased capillary formation in ischemic muscle of mice with higher platelet ***,thrombin activity was significantly higher in the mice with higher platelet *** with higher level of fV demonstrated significantly higher pro-migratory activity in an endothelial cells migration *** findings suggest that platelet-derived fV contributes to the control of angiogenesis,in addition to its role in *** stimulation is likely associated with thrombin generation due to platelet-derived fV.
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