| Stroke,also known as cerebrovascular accident,is a sudden cerebrovascular disease caused by damaged cerebral circulation,including cerebral artery stenosis or rupture caused by various reasons.At this time,it will cause various types of cerebral blood circulation disorders.The clinical manifestations of stroke are transient or permanent brain dysfunction,with high disability and mortality.According to the different types of manifestations,stroke can be divided into two types,one is ischemic stroke,the other is hemorrhagic stroke,and the former accounts for a larger proportion of clinical stroke patients.Post-stroke cognitive impairment(PSCI)is a common post-stroke complication that seriously affects the overall rehabilitation and daily life of stroke patients.Therefore,early diagnosis and early intervention are of great significance.Enriched environment(EE)is a behavioral intervention therapy which is mainly based on sensory,sports and social stimulation.At present,EE has been used in the basic and clinical research of various nervous system diseases.The results showed that the pathogenesis of PSCI was related to neuroinflammation,and miR-146a-5p could play a regulatory role in the immune inflammatory response.Therefore,this study takes PSCI as the research object,through clinical research and animal experiment,and takes miR-146a-5p-inflammatory response as the main line,explores the mechanism of the influence of enriched environment on PSCI,and provides a new rehabilitation method and theoretical basis for the treatment of PSCI.Chapter 1 Clinical ResearchThe role of miR-146a-5p in enriched rehabilitation training to improve the cognitive function of patients with post-stroke cognitive impairmentObjective:To observe the effects of enriched rehabilitation training on cognitive function,plasma miR-146a-5p and inflammatory factors in patients with Post Stroke Cognitive Impairment(PSCI).Methods:The case group adopts a random number table method,and finally 58 patients with PSCI in the Department of Rehabilitation Medicine of our hospital are divided into enriched rehabilitation training group(rich group,n=29)and traditional rehabilitation training group(traditional group,n=29);The age-matched control group(AMC group,n=30)at the same time in the hospital physical examination center.Before and 8 weeks after rehabilitation intervention,Montreal Cognitive Assessment Scale(MoCA),Digit Span Test(DST),Trail Making Test Part A-B(TMT)and Modified Barthel Index(MBI)were used in case group to evaluate the neurocognitive function and activities of daily living of the patients,and the plasma levels of miR-146a-5p,IL-6 and TNF-α were measured before and after the intervention.Spearman correlation analysis was used to detect the correlation between the changes of plasma miR-146a-5p and the scores of each scale.The AMC group was tested with MOCA scale and the same plasma indicators as the case group.Results:Before rehabilitation intervention.MOCA scores,DST scores.TMT A-B scores.BMI scores,plasma miR-146a-5p,IL-6,and TNF-α levels were not statistically different between the two groups of cases(p>0.05);And at baseline,the plasma miR-146a-5p expression levels of the two groups of cases were lower than those of the control group(P<0.05),and the plasma levels of IL-6 and TNF-α were higher than those of the control group(P<0.05).After 8 weeks of rehabilitation intervention,scale scores of both groups were improved compared with those before treatment(p<0.05);Moreover,MOCA scores and MBI scores in enriched group were higher than those in the traditional group,(p<0.05),The time consumption of TMT-A and TMT-B were lower than the traditional group(p<0.05),the Digit Span Test Scores were not statistically significant between the two groups(p>0.05).After 8 weeks of rehabilitation intervention,the relative expression of miR-146a-5p was up-regulated in both groups(p<0.05),while IL-6 and TNF-α were down-regulated(p<0.05);the relative expression of miR-146a-5p in enriched group was higher than that in traditional group(p<0.05),plasma TNF-α was lower than that in traditional group(p<0.05),plasma IL-6 was lower than that in traditional group,but the difference was not statistically significant(p>0.05).In all case groups,the changes in plasma miR-146a-5p before and after the intervention were positively correlated with the changes in MOCA scores and Digit Span Test Scores(r=0.603,p<0.05;r=0.348,p<0.05),and negatively correlated with the changes of time consuming of TMT-A and TMT-B(r=-0.342,p<0.05;r=-0.728,p<0.05),and no significant correlation with MBI score(r=0.152,p>0.05).Conclusion:Enriched rehabilitation training can improve the cognitive function of PSCI patients,which may be related to the significant increase of plasma miR-146a-5p levels and the reduction of the body’s inflammation.Chapter 2 Animal ExperimentEffects of miR-146a-5p regulated by different living environment on hippocampal inflammation and cognitive function in stroke miceObjective:To explore the mechanism of the enriched and isolated environment on the cognitive function and hippocampal inflammation in stroke mice.Method:The stroke model of 70 clean-grade C57BL/6 mice was established by photothrombosis.After 24 hours of modeling,66 mice were randomly divided into stroke standard environment group(SE group,n=22),stroke enriched environment group(EE group,n=22)and stroke isolation housing group(IH group,n=22).Another 22 C57BL/6 mice were selected as sham group.After 28 days of living in the corresponding environment,the cognitive function of mice in each group was detected by water maze;the morphological changes of hippocampal CAI area were observed by HE and Nissl staining;the expression levels of mir-146a-5p and TRAF6 mRNA were detected by qPCR technology;Western blot was used to detect the expression of TRAF6/NF-κB signaling pathway protein,TNF-α and IL-6 in hippocampus of mice.Result:After the intervention,compared with sham group,the escape latency of water maze in SE group was significantly increased(P<0.05),the number of crossing platform was significantly decreased(P<0.05),the pathological damage of hippocampal CA1 area and the decrease of Nissl body were observed(P<0.05),the expression of TRAF6 and nuclear NF-κBp65 protein in hippocampus were up-regulated(P<0.05),and the levels of inflammatory factors IL-6 and TNF-α were increased(P<0.05);TRAF6 mRNA content and miR-146a-5p expression in hippocampus were increased(P<0.05).Compared with SE group,the escape latency of water maze in EE group was significantly decreased(P<0.05),and the number of crossing platform was significantly increased(P<0.05);the pathological damage of hippocampal CAI cells was alleviated,and the number of Nissl bodies was increased(P<0.05);the expression of TRAF6 and nuclear NF-κBp65 protein in hippocampus was decreased(P<0.05),and the levels of inflammatory factors IL-6 and TNF-α were decreased(P<0.05);The expression of TRAF6 mRNA decreased(P<0.05)and mir-146a-5p increased(P<0.05).Compared with SE group,the escape latency of water maze in IH group was significantly prolonged(P<0.05),the number of crossing platform was significantly reduced(P<0.05),the number of Nissl bodies in hippocampal CA1 area was significantly reduced(P<0.05),and the pathological damage was serious;the expression of TRAF6 and nuclear NF-KBp65 protein in hippocampus was significantly increased(P<0.05),and the levels of inflammatory factors IL-6 and TNF-α were significantly increased(P<0.05);the hippocampal TRAF6 mRNA content was increased(P<0.05),miR-146a-5p expression decreased(P<0.05).Conclusion:1.In the isolated environment,low levels of miR-146a-5p in the hippocampus of stroke mice aggravated neuroinflammatory responses and hippocampal cell damage,further leading to cognitive impairment in mice.2.Enriched environment can improve the cognitive function of stroke mice,which may be related to increasing the expression of miR-146a-5p in hippocampus,reducing the neuroinflammatory response and alleviating the pathological damage of cells. |
PDF Full Text Request