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Transcatheter Study On The Cerebral Protective Effect Of Ischemic Postcondition In T2DM Tree Shrews And The Analysis Of Related Factors In Clinic

Posted on:2018-08-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:L ZhaoFull Text:PDF
GTID:1314330518981135Subject:Surgery
Abstract/Summary:PDF Full Text Request
Diabetes and cerebral ischemia are closely related to the growing prevalence of both,and the body in the state of hyperglycemia,the organization of poor tolerance to ischemia and hypoxia,neurons can not be regenerated,low repair,combined with the complex structure of the brain itself The pathophysiological mechanism of cerebral ischemia,pathogenesis and recovery after cerebral ischemic injury is still unclear.Therefore,further study of diabetic cerebral ischemia under pathophysiological characteristic,reveal the mechanism of signal transduction and ischemic postconditioning regulation,targeted for cerebral ischemia of non-drug resistance protection strategy,has become the current basic and clinical brain protection study important issue to be solved,It is also the key to the design of experiment.Objective:More comprehensive understanding of diabetes,cerebral ischemia and ischemic postconditioning intervention under differentially expressed genes,analysis of post-response to the regulation of differential gene expression and possible protective mechanisms of the brain to reveal the post-adaptation brain protection signal channel and regulatory link,Aiming to confirm that ischemic postconditioning can effectively activate the mechanism of endogenous neuroprotection of the body in order to provide a new way for the prevention and treatment of ischemic stroke in clinical diabetic patients,and to open up new directions for the development of new clinical treatment methods,For the future of diabetic chronic vascular complications"non-drug treatment" strategy to lay a solid theoretical basis and experimental basis.Methods:In this study,we used high-fat diet combined with intraperitoneal injection of STZ to construct low-grade primate-tree shrew diabetes model.Cortical thrombotic cerebral ischemia was established by photochemical induction method.After 4 hours of ischemia,(4h),brain edema peak(4h),the level of cerebral edema,and the level of cerebral edema(P<0.05).Conclusion:When the ischemic side of the common carotid artery(5min,5min,repeat 3 cycles)(24h)and convalescence(72h).The metabolic status of the body was measured by serum biochemical markers.TTC staining,HE staining and electron microscopy were used to observe the changes of the body's metabolic status at 24 hours after the most prominent clinical manifestations.Structural observations were performed on ischemic brain injury.The transvaginal cerebral cortex was the most severe and the most representative ischemic center was used as the observation object.Results:1.The changes of blood biochemical parameters:the weight of shrews in each group(body weight after admission),blood glucose(blood glucose after admission,bilirubin,total cholesterol,triglyceride,low density lipoprotein cholesterol,C protein Differences(P<0.05).Compared with DM + cerebral ischemia group,low-density lipoprotein cholesterol and C-reactive protein were decreased(P<0.05),but still higher than that of sham operation group.2.TTC staining,HE staining and ultrastructural examination showed that the lesions were obvious in the cortex of the irradiation area after 24 hours of ischemia.The diabetic group increased the lesion and the area of the infarct was the largest.After treatment,the area of cortical infarct size was reduced,ischemic injury was restored,and the infarct size decreased.3.Differences in gene analysis showed that there were 769 differentially expressed genes(508 genes up-regulated and 261 genes down-regulated)in the DM group and the sham-operated group.There were 938 differentially expressed genes in the cerebral ischemia group and the sham-operated group(732 genes(1414 genes were up-regulated and 1205 genes were down-regulated).There were 2206 differences in DM + cerebral ischemia group and cerebral ischemia group(P<0.05),and there were 2619 differentially expressed genes in DM + cerebral ischemia group and DM group There were 520 differentially expressed genes(203 genes were up-regulated and 317 genes were down-regulated)in DM + cerebral ischemia +ischemic PC group and DM + cerebral ischemia group(1118 genes were up-regulated and 1088 genes were down-regulated).As a result of the large number of differentially expressed genes,the results are only listed in the first and second changes in the expression of multiple changes in the first three genes,namely DM group and sham operation group,cerebral ischemia group and sham operation group,DM + cerebral ischemia group DM group,DM + cerebral ischemia group and cerebral ischemia group and DM + cerebral ischemia + ischemic PC group and DM +cerebral ischemia group comparison gene.4.GO analysis showed that there was no significant difference in BP,CC and MF between the postconditioner group and DM + cerebral ischemia group,and the padj values were more than 0.05.The down-regulated BP was mainly in the immune system(padj<0.05).The major genes involved were receptor-type tyrosine-protein phosphatase C(PTPRC),TNF13,CXCL2 and immune response(padj<0.05).The main genes involved were C1QB,CCL5,CCAAT/enhancer-binding protein delta(CEBPD);CC had no significant difference(padj>0.05)(Pk),tumor necrosis factor receptor binding(padj<0.05).The main genes involved were C1QA,TNF14,TNF13,tumor necrosis factor(P<0.05).The main genes involved were C1QB,C1QC,TNF13 and cytokine receptor binding(padj<0.05).The main genes involved were TNF14,CXCL2 and C1QA.5.KEGG analysis showed that there were 0 differences(padj>0.05)in the post-adaptation group and DM + cerebral ischemia group(Fig.47A).There were 13 differentially differentiated signaling pathways(padj<0.05),which were NF-?B signaling pathway,TNF signaling pathway,Fc gamma R-mediated phagocytosis.Conclusion:1.The model can be used to simulate and reflect the real process of the development of human disease.It has better anatomy and neurobiology and high practical value.The model can be used to simulate and reflect the development of human disease.2 The local thrombotic cerebral ischemia model of tree shrew induced by high fat induction and photochemistry was close to that of human focal cerebral ischemia,and the "realistic" of simulated clinical study was strong.3.By ischemic postconditioning treatment,can reduce the cerebral cortex infarct size of the tree shrew,so that the nerve is improved,in order to achieve the protection of brain tissue damage.4.CC motif chemokine chemokines can induce the release of various bioactive substances such as complement components,IL-1(IL-1),interferon-y(IFN-y)and tumor necrosis factor-As well as reactive oxygen species,etc.,involved in diabetes and cerebral ischemia.5.The up-regulation of NF-kappa B signaling pathway and TNF signal pathway in cerebral ischemia may be related to the early stage of cerebral ischemia and apoptosis.And PC treatment,the reduction of these two channels in a large number of genes,reducing the cerebral ischemia on the cerebral cortex damage.Both type 1 and type 2 diabetes(T2DM)are important independent risk factors for atherosclerosis and cerebrovascular disease.Type 2 diabetes in patients with about 20%to 40%of the possible complications of cerebrovascular disease,ischemic cerebrovascular disease is the most common early onset[1],clinical symptoms are relatively complex and rapid progress,more complications,treatment Relatively difficult,clinical efficacy and poor prognosis.Due to the lack of basic and clinical integration and the basic research to the clinical application of the transformation of exploration,so that there is no clinical treatment for diabetic vascular disease directly and effective targeted therapeutic drugs and means.Therefore,this article on T2DM patients with ischemic cerebrovascular disease distribution and risk factors were analyzed,and through case-control study methods to patients with ischemic cerebrovascular disease as a case group,without complicated ischemic cerebrovascular disease patients The aim of this study was to provide a scientific basis for the screening and early prevention and control of ischemic cerebrovascular disease in T2DM patients,and to compare the blood biochemical indexes and clinical features of the two groups.Objective:More comprehensive understanding of T2DM complicated with ischemic cerebrovascular disease risk factors,so as to T2DM patients with ischemic cerebrovascular disease screening and early prevention and control to provide a scientific basis.While exploring the feasibility of combining basic research with clinical practice,it is helpful to clarify the pathophysiologic mechanism of different target organ damage in T2DM patients,and to find out the effective risk factors for the future,and to improve the basic research Of the transformation to provide reference for the research model,has important value and application of exploration.Methods:According to the database of patients with type 2 diabetes mellitus in the second affiliated hospital of Kunming Medical University,the distribution characteristics and risk factors of ischemic cerebrovascular disease in T2DM patients were analyzed and analyzed by case-control method.Cerebrovascular disease as a case group,not complicated by ischemic cerebrovascular disease in patients with control group,compared the two groups of blood biochemical testing indicators and clinical features.The related factors of T2DM complicated with ischemic cerebrovascular disease were analyzed by regression analysis.The related risk factors of T2DM complicated with ischemic cerebrovascular disease were analyzed.Results:Logistic regression analysis showed that the variables were adjusted by the method of Backward:LR,and the dosage of 0.05 was included in the model:the severity of daily affairs,the time of sleep,the high blood pressure,hyperuricemia,hyperlipidemia,Atherosclerosis,carotid intima thickness,body mass index,glycosylated hemoglobin,rigidity index and fibrinogen,a total of 11 variables,that is,11 variables and the occurrence of ischemic cerebrovascular disease.Among them,the sleep time,hyperuricemia,body mass index,smoking regression coefficient were negative,Exp(?)is less than 1,indicating that the above factors and T2DM patients with ischemic cerebrovascular disease associated with low risk.The severity of daily routine,hypertension,hyperlipidemia,carotid intima thickness,glycosylated hemoglobin,rigidity index and fibrinogen,partial regression coefficients were positive,Exp(?)greater than 1,indicating the above factors and T2DM Patients with high risk of ischemic cerebrovascular disease associated with type 2 diabetes with ischemic cerebrovascular disease risk factors.Conclusion:1.Adverse lifestyle induced and aggravated the development of chronic complications associated with diabetes,should be early intervention.2.Arterial medial thickening,hypertension,hyperlipidemia,HbA1C,rigidity index and Fib are risk factors for T2DM with ischemic cerebrovascular disease.3.The precise control should be done around the above risk factors for the screening and prevention in T2DM patients with ischemic cerebrovascular complications.4.1t is important to do carotid Caudal ultrasound regularly,as a screening for atherosclerosis,arterial intima thickening and predict the occurrence of routine strokes,to prevent T2DM patients with ischemic cerebrovascular disease.
Keywords/Search Tags:Tree shrew, Photochemistry, Diabetes mellitus, Cerebral ischemia, Ischemic postconditioning, Transcriptome sequencing, Diabetes, cerebrovascular ischemic disease, risk factors, atherosclerosis, carotid intima thickness
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