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Special Blood Purification Therapy Of Vascular Endothelial Function In Basic And Clinical Research

Posted on:2007-06-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:J XueFull Text:PDF
GTID:1114360212984640Subject:Medical renal disease
Abstract/Summary:PDF Full Text Request
Section One Influence of CVVH on the endothelial cell function in SIRS/Sepsis patientsObjective: Endothelial activation or dysfunction played an important role during the pathological progression of SIRS/Sepsis patients. Efforts were made to investigate the effects of CVVH on the endothelial function of SIRS/Sepsis.Methods: Plasma concentration of the sTM, sICAM-1, sE-selectin were measured before and after CVVH treatment in 15 SIRS/Sepsis patient by ELISA. 10% concentration serum of pre- and post-treatment were incubated with HUVEC. After 24 hours the proliferation, permeability of endothelial cells were test by MTT colorimetric method and Falcon? cell culture inserts. And also the levels of sTM, sICAM-1 in the supernate of cell culture were measured respectively. The APACH II scores were used to evaluate the treatment effects.Results: APACH II scores were much better on the 4th day of post-treatment in 8 SIRS patients, but much worse in 7 sepsis patients. The concentration of sTM, sICAM-1, sE-selectin in SIRS/Sepsis patients were significantly higher than in control. And also they were higher in sepsis patients compared with SIRS patients. And CVVH did not influence the above-mentioned index. The endothelial proliferation was no difference between SIRS and normal group, whereas it was much lower in sepsis group. And it was not be improved by CVVH treatment. The serum of SIRS/Sepsis patients increased the endothelial cells permeability a lot. But for SIRS patients, the serum of post-treatment decreased the permeability of endothelial cells, but no changes for sepsis patients. In sepsis group, the serum of pre- or post-treatment all stimulated the endothelial cells secreting the sTM and sICAM-1, But in SIRS group, only sICAM-1 except for sTM.Conclusion: Endothelial activation and dysfunction were found in SIRS/Sepsis patients. CVVH only partly improved the endothelial function, not including the sepsis patients.Section Two The effect of HDF with VitC dialysate on the endothelial functionObjective: To explore the effect of VitC dialysate HDF on the endothelial function compared with the regular HDF in prospective, self-cross way. Methods: 10 stable maintenance hemodialysis patients were enrolled in the research. Their plasma level of total ascorbic acid (TAA), DHAA/TAA, a-tocopherol, advanced oxidative protein products(AOPP) and malondialdehydea(MDA) were detected pre-and post-treatment of regular HDF or VitC dialysate HDF. And also the flow dependent vascular dilation (FDD) was measured by high-resolution B-mode ultrasonograph. The pre- and post-treatment serum was incubated with HUVEC, and then the sICAM-1, MCP-1 in the supernate and the eNOS expressed in the endothelial cell were tested respectively.Results: After regular HDF, the plasma TAA, a-tocopherol, DHAA decreased significantly except for AOPP, DHAA/TAA, MDA. But after VitC dialysate HDF, plasma TAA,DHAA were much higher than before, and a-tocopherol, DHAA/TAA were lower. FDD were markedly impaired after regular HDF, but interestingly, no change after VitC dialysate HDF. The post-treatment serum of regular HDF stimulated the endothelial cell secreting the sICAM-1, MCP-1, but it was absolutely different from the VitC dialysate HDF. The expression of eNOS in the endothelial cell kept stable after cultured with the post-treatment serum of regular HDF or VitC dialysate HDF.Conclusion: The regular HDF impaired the endothelial function probably for the VitC losing and high oxidative stress. The VitC dialysate HDF maybe was the good way to dissolve the problem partly.Section ThreeThe therapeutic effects of the H.E.L.P system in the patients with acute ischemic stroke and its influence on the endothelial functionObjective: To evaluate the therapeutic effects of the H.E.L.P system (heparin-induced extracorporeal low-density lipoprotein-apolipoprotein(a)-fibrinogen precipitation) in patients with acute ischemic stroke and probe into its possible mechanism. Method: 10 patients with acute ischemic stroke were included and received the H.E.L.P therapy in addition to low molecular weight dextran, salvia miltiorrhiza and aspirin. Matched with gender, age, European Stroke Scale (ESS) and fibrinogen, 20 patients with cerebral infarction treated with low molecular heparin were chosen as control during the same period. We were to compare the efficacy and prognosis between the two groups, and to determine some cytokine in the supernate of HUVEC and the endothelial permeability, which was cultured with the serum of the patients before and after the H.E.L.P therapy.Results: Twentyone days after treatment, ESS scores in the H.E.L.P group (70.4±23.06) were higher than those in control group (60.7±18.94), but there was no statistical significance (P>0.05). In the H.E.L.P group, total efficacy rate reached 60% (6 cases of recovery and efficacy, 4 cases of inefficacy), while it was 40% in control group (8 cases of recovery and efficacy, 12 cases of inefficacy). There was no significant difference between both groups by chi-square test (P>0.05) and Logistic Regression analysis (P=0.305). But the efficacy rate in the H.E.L.P group (60%) was markedly higher than that in control group (20%) according to ADL scores (P<0.05), and Logistic Regression analysis revealed P=0.036. Pearson correlation analysis showed that duration of therapy was correlated to final ADL scores (P=0.044), and the mean treating time was 14.08±3.41 hours in patients who achieved efficacy criteria. After treatment, no difference was found in hemorheology, fibrinogen, blood lipid, OX-LDL, and CRP in control group, while a significant decrease in the H.E.L.P group immediately after treatment (P<0.01). When cultured with the serum of the patients after the H.E.L.P therapy, the concentration of sTM, sICAM-1, MCP-1 in the supernatant of HUVEC remained unchanged at 24 hours (P>0.05), while it was remarkably higher when HUVEC was cultured with the serum of the control and patients before the H.E.L.P therapy only but for sTM(P<0.01). And meanwhile theendothelial permeability was improved after the HELP treatment.Conclusion: With the effects of improving hemorheology, decreasing acute phasereactive protein, ameliorating endothelial cell function, H.E.L.P system may be anovel therapy for acute ischemic stroke.
Keywords/Search Tags:Endothelial cell, Continuous venous-venous hemofiltration, Thrombomodulin, Intracellular adhesion molecule-1, E-selectin, Hemodialysis filtration, oxidative stress, endothelial cell, HELP system, acute ischemic stroke
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