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Research Of The Relationship Between Cytokines And NF-kB/JNK Signaling Pathway In The Process Of ASD Catheter Block

Posted on:2018-05-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:S Y FanFull Text:PDF
GTID:1314330515975279Subject:Surgery
Abstract/Summary:PDF Full Text Request
ObjectiveTo explore the changes of cytokines in patients with congenital heart disease(ASD)before and after catheterization,and to explore the molecular mechanism of this change through animal experiments.MethodsThis paper retrospectively analyzed the cases of treatment of 200 patients with congenital heart disease atrial septal defect(ASD)from September 2013 to December 2015.As a study group,all patients underwent catheterization The levels of TNF-?,IL-6,IL-8 and IL-10 in serum were measured by enzy me-linked immunosorbent assay(ELISA)after 6 months of treatment and 12 months after treatment.And the content of cytokines in serum was detected a s 200 cases of normal healthy subjects as control group.100 samples were randomly selected from the study group and the contro l group.Immunohistochemical staining,immunoprecipitation test and real-time quantitative PCR were used to detect the cytokines in the peripheral blood m ononuclear cells Molecular mechanism.Using Hybrid method to set up the animal model of young pigs of cong enital heart disease(ASD),40 successful build model of congenital heart disea se(ASD)in young pigs,40 only build successful young pigs can be divided i nto A,B,C,D four groups,each group of 10 young pigs.And 10 normal young pigs to determine serum cytokine levels as blank control group.Group A of the model built with catheter closure treatment after surgery and in six months continuous injection of normal saline as control group,group B with in 6 months after the operation,the process of building the model of continu ous injection of PDTC drugs(NF-KB inhibitors),Group C of the model cons truction of continuous injection of SP600125 within 6 months after surgery(J NK inhibitors),group D within 6 months after the operation,the process of b uilding the model of continuous injection of PDTC drug(NF-KB inhibitor)an d SP600125(JNK inhibitors),preoperative and postoperative measured six mo nths after the change of cytokines in the body,young pigs to explore the cat heter block before and after the treatment of congenital heart disease in patie nts with the molecular mechanism of the change of cytokines in the body.ResultsThe results showed that between September 2013 and December 2015 in our hospital for treatment of the team before operation,200 cases of congenital heart disease(ASD)than the control group,serum TNF-?,IL-6,IL-8 inflammatory cytokine content such as a rising significantly,and anti-inflammatory cytokines such as IL-10 significantly reduced;Using catheter closure after 6 months of treatment group patients serum TNF-?,IL-6,IL-8 and other inflammatory cytokines compared with preoperative reduced significantly,and anti-inflammatory cytokines such as IL-10 compared with preoperative must rise;After 12 months of treatment in serum TNF-?,IL-6,IL-8,IL-10 cytokines such as return to normal levels.Team in patients with preoperative than control group in peripheral blood mononuclear cell sample of NF-KB signaling pathways and the activation of JNK signaling pathways were significantly,postoperative group samples of peripheral blood mono nuclear cells of NF-KB signaling pathways and JNK signaling pathway than the control group had no obvious activation.Real-time fluorescent quantitative PCR detection results show that the team preoperative TNF-?,IL-6,IL-8 and other inflammatory cytokine mRNA level rise significantly,IL-10 and anti-inflammatory cytokine mRNA levels were significantly reduced;Postoperative TNF-?,IL-6,IL-8,IL-10 such as cytokine mRNA level back to normal levels.Immunohistochemical staining results showed that the team in patients with preoperative samples than control group in peripheral blood mono nuclear cells NK-kB cell nucleus staining positive rate is higher,there was no obvious difference in with the control group;Team in patients with preoperative more samples of peripheral blood mono nuclear cells in the control group p-c-Jun staining positive rate higher,postoperative team more samples of peripheral blood mono nuclear cells in the control group p-c-Jun staining positive rate has no obvious difference.Using Hybrid method to set up the animal model of young pigs of congenital heart disease(ASD),40 successful build model of congenital heart disease(ASD)in young pigs,40 only build successful young pigs can be divided into four groups.Four groups of young pigs in congenital heart disease(ASD)after model building are TNF-?,IL-6,IL-8 and inflammatory cytokine levels rise,IL-10 and the symptoms of anti-inflammatory cytokine levels drop.Duct sealing treatment of the control group after treatment catheter closure basic back to normal levels;TNF-? PDTC injection group,IL-6,IL-8 and the levels of inflammatory cytokines is normal levels have increased;TNF-? SP600125 injection group,IL-6,IL-8 and the levels of inflammatory cytokines is normal also have a certain rise;PDTC and joint injection SP600125 group of TNF-?,IL-6,IL-8 and the levels of inflammatory cytokines and there was no evident difference compared to normal levels.ConclusionOur results showed that patients with congenital heart disease(ASD)have a certain degree of immune activation,causing rising levels of inflammatory cytokines of patients,anti-inflammatory cytokine levels drop,produce certain inflammation phenomenon;After catheter closure after treatment,the patient's immune system is gradually restored.Cytokine changes caused by congenital heart disease(ASD)patients may be through the NF-kB signaling pathways and JNK signaling pathway under the synergy of implementation.The results of our study is to explore the mechanism of congenital heart disease(ASD)patients to an imbalance in the body's immune,provides a theoretical basis for the further found that the treatment of congenital heart disease treatment has provided the theoretical foundation and scientific basis.
Keywords/Search Tags:congenital heart disease, atrial septal defect, transcatheter closure, cytokines, animal model, NF-kB Signaling Pathway, JNK Signaling Pathway
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