Endothelial cell injury with inflammatory cytokine and coagulation in patients with sepsis

BACKGROUND:Current studies on CD62 P have focused mainly on cardiovascular diseases,while only few studies have evaluated the effects of CD62 P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation.This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P(s-CD62P) in plasma and its mechanism in patients with sepsis,thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62 P.METHODS:A total of 70 critically ill patients with systemic inflammatory response syndrome(SIRS) admitted to intensive care unit(ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to the diagnostic criteria of sepsis/SIRS,the patients were divided into two groups:a sepsis group(n=38) and a SIRS group(n=32).Another 20 healthy volunteers served as a control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of the patients including age,sex,body mass index(BMI),smoking and alcohol addict were compared among the groups.Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzymelinked immunosorbent assay(ELISA) to detect the plasma levels of S-CD62 P,TNF-α,and hs-CRP.And variables of coagulation function such as platelet(PLT),prothrombin(PT),activated partial thromboplastin time(APTT),D-dimer and antithrombin-Ⅲ(AT-Ⅲ) were analyzed during 24 hours after admission to ICU.Meanwhile sequential organ failure assessment(SOFA) score of critically ill patients was evaluated.Data were expressed as meanistandard deviation and were statistically analyzed by using SPSS 17.0statistical software.The differences in plasma levels of S-CD62 P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test.The relations between S-CD62 P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis.Changes were considered as statistically significant if P value was less than 0.05.RESULTS:Compared with the control group and SIRS group,the sepsis group demonstrated significantly higher levels of S-CD62 P,TNF-a and highly sensitive C-reactive protein(hs-CRP)(PO.05).The plasma levels of D-dimer,PT,and APTT in the sepsis and SIRS groups were significantly higher than those in the control group,while the platelet count and the activity of AT-Ⅲ were obviously lower(P<0.05).In the sepsis group,the plasma levels of hs-CRP and TNF-a were positively correlated with PT,APTT,and D-dimer,and negatively correlated with AT-Ⅲ and PLT(P<0.05).The plasma levels of S-CD62 P were significantly correlated with the plasma levels of TNF-a,hs-CRP,D-dimer,PT,and APTT,whereas they were correlated negatively well with PLT and AT-Ⅲ(P<0.05).CONCLUSIONS:The concentration of plasma S-CD62 P is elevated as a early biomarker in patients with sepsis,and it serves as one of the pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promote each other,aggravating the severity of sepsis.Plasma S-CD62 P may be an important factor for the development of coagulation and inflammatory reaction.

HSP70 regulates Bcl-2 to inhibit endothelial cell damage in emergency sepsis patients

Objective:To analyze the mechanism of HSP70 regulating endothelial cell injury in patients with acute sepsis.Methods:From February 2017 to December 2018,3 patients with acute sepsis in our hospital were selected as the observation group,and 3 patients with fracture undergoing surgical treatment were selected as the control group.The endothelial cells were extracted and divided into blank subgroup,10 mg/L,50 mg/L and 100 mg/L subgroups.The cell viability of each group was detected by MTT,the nucleus morphology was observed by fluorescence microscope,and autophagosomes of endothelial cells were observed by transmission electron microscope,and then the level of Bcl-2,Beclin-1 andβ-actin protein expression were detected.Results:HSP70 intervention can effectively improve the endothelial cell vitality of patients with acute sepsis.The cell viability of 100 mg/L subgroup was the highest in the observation group and the control group,and the cell viability of the blank subgroup was the lowest,and the difference was statistically significant(P<0.05).Compared with the control group,the endothelial cell nuclear defect of acute sepsis patients was serious.HSP70 intervention can effectively improve the nuclear morphology,autophagy morphology and structural morphology,and the 100 mg/L subgroup had the best nuclear morphology and autophagy morphology.HSP70 intervention can effectively improve the levels of Bcl-2 and beclin-1 in endothelial cells of patients with acute sepsis.The levels of Bcl-2 and beclin-1 were the highest in the 100 mg/L subgroup of the observation group and the control group,and the lowest in the blank subgroup,and the difference was statistically significant(P<0.05).Conclusion:HSP70 can effectively regulate the level of Bcl-2 in endothelial cells of patients with acute sepsis,which effectively inhibit cell apoptosis and alleviate cell skin damage.

Related factors of coronary no-reflow phenomenon and progress of traditional Chinese medicine treatment

Coronary no-reflow phenomenon belongs to a type of coronary microcirculation disturbance,and its main pathogenic factors are vascular endothelial cell injury,microembolism and inflammatory reaction,which are corresponding to the pathogenesis of choroid injury,blood stasis and heat toxin in traditional Chinese medicine,such as NO,ET-1,chemokine,IL and other cytokines.The degree of improvement of patients'symptoms and laboratory examination data provide a basis for traditional Chinese medicine compound prescription,monomer and traditional Chinese medicine characteristic therapy for the treatment of no-reflow phenomena(NRP).Combined with related factors,the author summarizes the research progress of traditional Chinese medicine treatment of NRP in recent years,in order to provide clinical reference.

Role of endoplasmic reticulum stress protein C / EBP homologous protein-10 in ischemia and hypoxia induced human aortic endothelial cells injury

Objective To investigate the expression of endoplasmic reticulum stress(ESR)marker C/EBP homologous protein-10(CHOP-10)in the human aortic endothelial cells(HAEC)under the ischemia and hypoxia stress and to study the effects of atorvastatin on the process.Methods The cultured HAEC were divided into normal control group,ischemia/hypoxia model group。

Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells

Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.