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[ ABSTRACT] AIM: To explore the role of chemokine receptor CXCR 4 in the pathogenesis of protein C system (PCS) in ulcerative colitis (UC).METHODS:In vivo, the mice were divided into control group and UC group .The mac-roscopic score, microscopic score and ulcer index were assessed .The mRNA levels and activity of myeloperoxidase ( MPO) , cyclooxygenase-2 ( COX-2 ) , stromal cell-derived factor-1α( SDF-1α) and monocyte chemotactic protein 1 (MCP-1) both in colonic tissue and plasma were determined .The expression and location of CXCR4,β-arrestin, p-JNK, endothelial cell protein C receptor (EPCR) and thrombomodulin (TM) were detected.The activity of protein C (PC) and protein S ( PS) was measured in each group .In vitro, mouse colonic microvascular endothelial cells were isolated , cultured and identified.Both CXCR4-overexpressing and CXCR4-silencing colonic mucosa microvascular endothelial cells were con-structed.The effects of SDF-1αon the protein levels of EPCR , TM,β-arrestin and p-JNK, and on the activity of PC , PS and activated protein C ( APC) were observed .RESULTS:Compared with control group , UC mice showed increased gross score, histopathological score and ulcer index (P<0.05).The mRNA levels and activity of MPO, COX-2, SDF-1αand MCP-1 in colon and plasma were increased (P<0.01).The protein levels of CXCR4,β-arrestin and p-JNK were up-regu-lated, EPCR expression was down-regulated in colon, and the activity of PC and PS in plasma was decreased (P<0.05 or P<0.01).CXCR4 overexpression further aggravated SDF-1α-induced PCS inhibition in colonic mucosa microvascular en-dothelial cells, and further up-regulated the protein levels of β-arrestin and p-JNK (P<0.05).CONCLUSION:PCS is inhibited in UC.CXCR4 is involved in the regulation of PCS inhibition by mediating chemokines and acting on colonic mu -cosa microvascular endothelial cells through β-arrestin-JNK pathway .
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Objective To investigate the changes of protein C and fibrinolytic system in patients with acute cerebrovasculer disease and the influence of intervened treatments on acute cerebral infarction(ACI).Methods Determinations of protein C(PC),protein S (PS),thrombomodulin(TM),Tissue-type plasminogen activater(t-PA),plasminogen activator inhabitor(PAI) were performed in patiens with acute cerebrovasculer disease and normal control(NC),then redeterminated these items after treatments in patients with ACI.Results PC,PS:The levels in patients with ACI were significantly lower than that in other groups.After dreatments,the levels in patients with ACI increased.There were no significantly discrepancy in acute cerebral hemorrhage(ACH) and lacunar cerebral infarct(LCI) compared with NC;TM:The levels in patients with ACH,ACI were significantly higher than that with LCI and NC.After dreatments,the levels in patients with ACI decreased;t-PA:The levels in patients with ACI were lower than NC,whereas the levels in patients with ACH increased.After dreatments,the levels in patients with ACI increased;PAI:The levels in patients with ACI were significantly higher than NC,and also found that the levels in patients with ACH and LCH were higher compared with NC.The levels in patients with ACI decreased after dreatments.Conclusions There are obviously abnormalities in plasma coagulative and fibrinlytic parameters in acute cerebrovasculer disease;To check the levels of PC,PS,TM,t-PA,PAI are important to predict the type of stroke,the seriousness of disease,the effect of treatment,prognosis of the cases and suggest that earlier treatments be important.
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The protein C system is a natural anticoagulant and profibrinolytic system consisting of protein C and protein S and thrombomodulin. Because the increased fibrinolysis and the decreased activities of coagulation factor V and VIII are observed in patients undergoing cardiopulmonary bypass, which are known main effects of achivated protein C, we studied the protein C system in the plasma of patients undergoing operation with extracorporeal circulation(ECC group, 31 patients) and without ECC(control group, 10 patients). The nature of the enhanced blood fibrinolytic activity that evolved during extraacorporeal circulation was charaacterized by significantincrease or fibrin degradation product(FDP) in ECC group(P<0.01) but not in control group. The changes of protein C system also showed only in ECC group. The changes of protein C system were most pronounced in the early phase of cardiopulmonary bypass. The changes of FDP ane protein C system were observed in both bubble and membrane oxygenator-used group, but the pattern and degree of change were quite different (P<0.01), i,e., more severe in membrane oxygenator-used group. These results confirm the disturbance of protein C system by extracorporeal circulation, which is possibly activated by the contact activation between blood and synthetic surface. So measurement of changes of protein C system could be used as a good method in the development of new materials for extracorporeal circulation.