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Experiment And Clinical Research On Adjusting The JNK Via Cerebral Vein Of I/R Aging Rat Brain Angiogenesis

Posted on:2017-04-03Degree:MasterType:Thesis
Country:ChinaCandidate:S H ZhaiFull Text:PDF
GTID:2334330491962316Subject:Internal medicine of traditional Chinese medicine
Abstract/Summary:PDF Full Text Request
BackgrandIschemic cerebrovascular disease(ICVD)is a kind of common disease,its morbidity,mortality,morbidity,recurrence rates are high,a serious threat to human health.In the treatment of ischemic cerebrovascular disease,ischemic brain tissue requires rapid recanalization,to restore blood oxygen supply,and cerebral blood flow can appear reperfusion injury aggravated phenomenon,namely the brain ischemia reperfusion(I/RIschemic reperfusion)damage,Is an important pathophysiological basis of cause various cerebrovascular disease.In general,cerebral ischemia injury refers to the interruption of cerebral blood flow,cerebral ischemic hypoxia and partial necrosis,and cause the corresponding neurologic symptoms.And after cerebral ischemia reperfusion injury is to restore blood supply,the excess free radicals attack this part to regain the blood supply of cells within the organization,this kind of injury,is called "tissue ischemia-reperfusion injury".In this study,cerebral vein group and the control way days 14 and 28 days after treatment of traditional Chinese medicine symptom classification of quantitative table score than before treatment were obviously improved(P < 0.01);Compared with the control group in the same time,cerebral vein group treatment for 14 days,28 days of TCM symptom rating scale scores were lower than that of control group(P < 0.05),suggesting cerebral vein can promote function recovery in patients with ischemic stroke.and vascular network reconstruction of ischemia area,need effective means of intervention to promote angiogenesis,but about the traditional Chinese medicine to promote angiogenesis research after I/R less reported.Therefore this topic from two aspects of animal experiment and clinical observation research,first of all,on the basis of the previous research,by observing the pathological changes of ischemic brain tissue in rat models,the new blood vessels field area and p-GSK-3 beta,effects of JNK signaling molecules expression changes,to explore the aging rats after I/R pathological physiology characteristic and traditional Chinese medicine pulse through the brain microvascular generation of promoting effect and possible mechanism of effect;At the same time observe cerebral vein clinical effects in elderly patients with ischemic stroke,to study the cerebral vein of protective effect of ischemic brain injury.Research shows that after cerebral ischemia reperfusion injury,itself can be adjusted through a variety of signal transduction pathways promote angiogenesis,to alleviate the reperfusion injury,promote the recovery of neural function.This self regulating angiogenesis process is slow,not enough to compensate the oxygen supplyObjectives: 1 By observing the groups of different time points after ischemia and reperfusion rats brain tissue injury pathological changes and new blood vessels field area,reveals the characteristics of aging in I/R injury rats and cerebral arteries and veins of brain protection.2 By measuring each different time points after ischemia and reperfusion rats ischemic half dark with p-GSK-3 beta,JNK expression changes,research on aging in I/R rats hindbrain,possible mechanisms of microvascular generation and the influence of cerebral vein tong.3 By comparing elderly ischemic stroke patients hospitalized in different time points after the NIHSS scale score and grade of TCM symptoms(qi and blood stasis)quantitative table score,to explore cerebral vein through clinical curative effect of senile cerebral infarction patients.Method 1 In SD rats as the research object,USES the middle cerebral artery occlusion(MCAO)of rat focal cerebral ischemia(I)3 h 24 h reperfusion(I/R),3 d,6 d,12 d animal models,respectively,by HE staining method to observe each group rats ischemic brain tissue at each time point characteristics and microvascular pathological damage area of change.2 Using immunohistochemical method to observe each group of ischemia rats in different time points half dark with p-GSK3 beta,JNK protein positive expression changes,study action mechanism of the cerebral arteries and veins through promoting angiogenesis.3 Clinical ischemic stroke patients can be divided into cerebral vein group and the control group,compare the two groups before treatment,treatment for 14 days,28 days NHISS scale quantitative table score and TCM symptom score,evaluate the clinical efficacy of cerebral arteries and veins.Results 1 Older I/R rats ischemic tissue pathological changes and microvascular field area change and the influence of cerebral arteries and veins through1.1 Brain tissue pathological changesMyocardial ischemic brain tissue in rats observed by each group found that in I3 h tissue edema;When I/R1 d,I/R3 d edema degree aggravating,visible blood vessels gap widened,nerve fiber disorder;most edema degree and appear when I/R6 d neurons,glial cell degeneration,necrosis,microvascular structure destruction;when I/R12 d edema disappeared basically,neurons and nerve fibers decrease,focal necrosis liquefaction.Compared with young model group,ischemic brain tissue pathological damage more serious aging model group,restore slower;Compared with the aged model group,cerebral vein through group and nim horizon pathological damage is lighter,recover quickly,especially in the cerebral vein group significantly.1.2 Microvascular changes areaComparative immunohistochemical test results found that: time point compared with young group,aging model group I/R 1 d,3 d,6 d,12 d field area are reduced(P <0.05,P <0.01),aging model group vascular field area in I/R 1 d peak,after gradually reduce;and aging model group than,cerebral vein group I 3 h,I/R 3 d,6 d,12 d vascular field area is increased(P <0.05,P <0.01);compared with nim horizon points at the same time,the brain increased pulse group I 3 h vascular field area(P <0.01)?2Aging rats after I/R p-GSK3 beta protein expression changes and cerebral vein on its expressionComparative immunohistochemical test results found that: Youth,aging control both p-GSK-3 beta protein expression of a small amount of;Compared with the corresponding control,youth,aging model group brain tissue at each time point p-GSK-3 beta express all increase;Young model group I/R1 d positive expression,as the extension of I/R time,positive expression showed increasing change,reach the highest,I/R6 d I/R 12 d have decreasing change;Compared with young model group the same time,the positive expression of aging model group were lower(P<0.05);Compared with aged model group the same time,cerebral vein group and nim horizon group p-GSK-3 beta positive expression were increased(p < 0.01).3 Aging JNK protein expression changes after I/R rats and cerebral vein on its expressionComparative immunohistochemical detection results found: youth,aging control are visible JNK protein expression of a small amount of;Compared with the corresponding control,youth,elderly brain tissue JNK expression at each time point model group were increased;Compared with young model group the same time,the positive expression of aging model group were lower(P < 0.05);Compared with aged model group the same time,cerebral vein through group and JNK positive expression of nim horizon group were increased(P < 0.01).4 In elderly patients with ischemic stroke NHISS rating scale,Chinese medicine symptom rating scale change and the influence of cerebral arteries and veins throughCompared with control group,cerebral vein NHISS each corresponding time point rating scale through group were lower than control group(P < 0.05);Group compared with control group,the cerebral vein through the corresponding time points of TCM symptom rating scale score lower than the control group(P < 0.05).Conclusion 1 Under the condition of the same injury,aging model group rats tissue damage appears earlier,the degree of heavy,and restore slower,microvascular generation;Tissue damage rats after drug intervention is lighter,repair faster,and increase new blood vessels diameter,blood perfusion increase effectively,especially in the cerebral vein group obviously,tip via cerebral vein can obviously improve the aging rats after I/R injury,promote effective angiogenesis.2 After I/R rats,the brain tissue in model group were obviously p-GSK-3 beta,JNK protein positive expression,compared with aged model group the same time,the protein expression level of drug intervention group were increased,especially in cerebral vein group significantly,reveal cerebral vein through promoting aging microvascular generated after I/R rats,the mechanism may be related to improve the p-GSK-3 beta,JNK protein expression.3 Clinical trial in elderly patients with cerebral infarction in the acute phase of disease NHISS scale quantitative table score and TCM symptoms score the highest,with the extension of time,the scores were lower,cerebral vein group change obviously,prompt brain via vein for the treatment of senile cerebral infarction has a satisfactory clinical effect.
Keywords/Search Tags:GSK3?, JNK, Naomaitong, angiogenesis, clinical research
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