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Study On The Expression And Clinical Significance Of MicroRNA-155 In Serum Of Patients With Acute Cerebral Hemorrhage

Posted on:2019-04-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:M J A B L Z MaiFull Text:PDF
GTID:1364330572460936Subject:Surgery
Abstract/Summary:PDF Full Text Request
With the aging of the social population,the incidence of hypertension and diabetes is increasing,and the threat of cardiovascular and cerebrovascular diseases to human society is becoming more and more obvious.The incidence of cerebral hemorrhage is increasing year by year.According to statistics,there are more than 1 million people worldwide suffering from intracerebral hemorrhage every year.The latest multi-center epidemiological survey in China,which lasted 10 years,showed that the incidence of cerebral hemorrhage accounted for 27.5% of the total stroke rate,far higher than 9%-18%in Western countries.ICH is a serious threat to human health.As so far,there is still a lack of effective treatment methods in clinical practice,so the mortality and disability rate are high,and more than 80% of surviving patients will have more serious neurological functions.Obstacles bring great pressure to patients,families,society,countries and so on.Cranial CT examination after intracerebral hemorrhage is an effective method for early diagnosis,but sometimes it can not completely reflect the degree of lesion and estimate prognosis.Therefore,it is of great clinical significance to find effective early markers that assist in determining the severity of brain injury.Clinically,the Glasgow coma scale(GCS)or the National Institute of Health stroke scale(NIHSS)score is generally used to judge the severity of cerebral hemorrhage and predict clinical prognosis,but there is still a lack of one.Serological indicators for accurately determining the prognosis of patients with cerebral hemorrhage.Currently,there are many models for predicting cerebral hemorrhage mortality and functional prognosis.Commonly used predictive models typically include routine neurological parameters,various clinical and laboratory parameters,and neuroimaging results.However,in some developing countries and some underdeveloped areas,there is alack of large-scale neurological imaging equipment(such as CT,MRI,etc.),and there are no neurologists in hospitals with poor medical conditions.The traditional predictive model is limited by various factors.This study intends to find a new serological marker that can be quickly detected and has less clinical specimens and simple and convenient detection methods,and explores the relationship between the marker and traditional nervous system parameters.The condition of acute hemorrhage in patients with cerebral hemorrhage is not the most serious period of the patient.As the course of the disease progresses,the patient's condition will increase after a few days of bleeding.It is speculated that this trend may be closely related to the secondary injury caused by cerebral hemorrhage.The mechanism of secondary injury is very complicated,including hematoma occupying after cerebral hemorrhage,metabolic abnormalities around the hematoma,and inflammatory reaction.More and more evidence indicates that the inflammatory response is closely related to the pathophysiological response of brain injury after cerebral hemorrhage.Inflammation is a common reaction after ICH.The ruptured blood vessels cause the infiltration of inflammatory cells and the activation of the complement system,and thrombin in the blood can also cause inflammation.Inflammation involves the secretion and release of cytokines,chemokines,and aggregation of immune cells.Recent studies have found that multiple microRNAs are involved in the regulation of inflammation-related genes and become another potential inflammatory mediator.A large number of studies have shown that the expression of miRNAs in the peripheral circulatory system changes dynamically after stroke,which indicates that these molecules play an important regulatory role in the occurrence and development of stroke.In addition,miRNAs are highly stable in the circulatory system,making them promising biomarkers for disease diagnosis and prognosis.MiRNA-155,as a multifunctional biotin,plays a role in many cell physiological processes,including growth,metabolism,inflammation,immune and hematopoietic differentiation and so on.The expression of miR-155 is closely related to the occurrence of many diseases,such as cardiovascular disease,cancer and viral infection.The up-regulation of miR-155 can be induced by different kinds of substances such as bacterial lipopolysaccharide(LPS)and inflammatory mediators(TNF-?,IFN-?).On the other hand,miR-155 may be used as a pro-inflammatory molecule to further aggravate the inflammatory process.Inflammation is the main pathophysiological mechanism of secondary injury aftercerebral hemorrhage,and then miR-155 is a pro-inflammatory molecule,therefore,this study intends to explore the peripheral blood of patients with cerebral hemorrhage serum miR-155 in the clinical relationship between severity of cerebral hemorrhage,to observe whether the serum levels of miR-155 in the prediction of the potential for cerebral hemorrhage patients with different prognosis.Objective:This study compared the differences in miRNA-155 expression levels in peripheral blood of patients with cerebral hemorrhage and normal physical examination,and the relationship between miRNA-155 expression levels and patient mortality and neurological prognosis after 6 months,and compared different bleeding volumes.Differences in miRNA-155 expression between the groups and patients in different GCS scoring groups,and comparing differences between groups,as well as analysis of correlations and differences,and then analyzing whether the level of serum miR-155 is relevant for patients with cerebral hemorrhage Prognosis has potential predictive power,as well as the relationship between blood loss,GCS score,and the expression of inflammatory cells and miRNA-155,aiming to provide new ideas for the diagnosis and treatment of cerebral hemorrhage diseases.Methods:This study used a prospective case-control study,using real-time quantitative PCR detection technology,80 cases of acute cerebral hemorrhage(not broken into the ventricle)diagnosed and conservatively treated in our department of neurosurgery and neurology from September 2016 to June 2017.The patients were included in the study,and the normal physical examinations of the physical examination at the same time in our hospital were used as controls.The expression of miRNA-155 in peripheral blood of 80 patients with acute cerebral hemorrhage and 30 normal subjects at the same time was measured,and GCS was used.The patient's level of consciousness was assessed by scoring.The neurological deficit was assessed using the National Institutes of Health Stroke Scale NIHSS.Patients were followed up 6 months later.The modified Rankin scale was used to assess the recovery of neurological function over 6 months and calculated.All-cause mortality,judgment of disease prognosis,statistical analysis of relevant data.Eighty patients with acute cerebral hemorrhage(not broken into the ventricle)were diagnosed according to the patient's CT findings according to the Tada formula.Accordingto the amount of bleeding,they were divided into the following three groups: SH(small amount of bleeding group)and MH(medium volume group).,LH(large amount of bleeding group);and the same time in the physical examination of the physical examination center of our hospital as a control.Real-time quantitative PCR was used to detect the expression of miRNA-155 in peripheral blood of 80 patients with acute cerebral hemorrhage and 30 patients in the same period.The GCS score was used to assess the level of consciousness of patients.The National Institutes of Health was used for stroke.NIHSS was used to assess neurological deficits in patients.Patients were followed up 6months later.The modified Rankin scale was used to assess the recovery of neurological function at 6 months and all-cause mortality was calculated to determine the prognosis of the disease.analysis.Eighty patients with acute cerebral hemorrhage(not ruptured into the ventricle)were divided into three groups according to the patient's GCS score: mild coma,moderate coma,severe coma,and compared with those who were in the physical examination center of our hospital.Real-time quantitative PCR was used to detect the expression of miRNA-155 in peripheral blood of 80 patients with acute cerebral hemorrhage and 30 normal subjects at the time of admission.The patients were followed up 6 months later and evaluated using the modified Rankin scale.The recovery of neurological function was calculated and the all-cause mortality was calculated,the prognosis of the disease was judged,and the relevant data were statistically analyzed.Results:In the case of 80 patients with acute cerebral hemorrhage and 30 patients with normal physical examination,the expression of miRNA-155 in patients with cerebral hemorrhage was significantly increased compared with the same period,and the difference was Significant statistical significance(P < 0.001).After 6 months,the expression of miRNA-155 in the cerebral hemorrhage death group was significantly higher than that in the surviving group,and the difference was statistically significant(P<0.01).Through the comparison of the area under the curve,we found that the expression of miRNA-155 has a good clinical significance for the prognosis of patients with cerebral hemorrhage,can distinguish patients and normal physical examination personnel,and has a predictive effect on the prognosis of patients(the area under the curve is 0.785).The specificity is0.714 and the sensitivity is 0.818).In the case of 80 patients with acute cerebral hemorrhage and 30 patients withphysical examination,there was no statistical difference in the clinical data.As the amount of bleeding increased,the expression of miRNA-155 increased,and in the large number of bleeding groups,moderate There was a significant difference in the expression of miRNA-155 between the bleeding group and a small amount of bleeding group(P<0.05).Plasma miRNA-155 levels in the death group were higher than those in the surviving patients(P<0.05),and as the amount of cerebral hemorrhage increased,the mortality increased and the expression level of miRNA-155 increased.It is positively correlated with the expression of miRNA-155.The expression levels of inflammatory cells such as neutrophils and lymphocytes and miRNA-155 in peripheral blood were positively correlated with the amount of cerebral hemorrhage,that is,as the amount of bleeding increased,the number of inflammatory cells and the expression of miRNA-155 also increased.And the differences between the groups have statistically significant significance.In the case of 80 patients with acute cerebral hemorrhage and 30 patients with normal physical examination,there was no statistical difference in the clinical data,and the expression of miRNA-155 decreased with the GCS score.As the GCS score decreased,the mortality rate increased gradually,and the expression level of miRNA-155 increased significantly.The expression levels of neutrophils,lymphocytes and other inflammatory cells and miRNA-155 were negatively correlated with GCS scores.As the GCS score decreased,the number of inflammatory cells and the expression of miRNA-155 also increased,and between groups.The difference is statistically significant.Conclusion:The expression of miRNA-155 in peripheral blood of patients with cerebral hemorrhage was significantly higher than that of miRNA-155 in the same period.After 6months of follow-up cerebral hemorrhage,the expression level of miRNA-155 in peripheral blood of patients in death group was significantly higher than that in survivor group.It can be speculated that the level of miRNA-155 in peripheral blood has a good predictive value for different clinical prognosis of patients with cerebral hemorrhage;while inflammatory cells(neutrophils,lymphocytes)of peripheral blood of each group also has a good predictive value for different clinical prognosis of patients according to the amount of bleeding.As the amount of bleeding increased,the number of inflammatory cells increased.The amount of bleeding was positively correlated with the expression of miRNA-155,mortality,and poor prognosis.That is,with the increase of blood loss,peripheral blood miRNA The expression level of miRNA-155 increased,and the mortalityof patients after 6 months increased.After cerebral hemorrhage grouped according to GCS score,the inflammatory cells(neutrophils,lymphocytes)of peripheral blood of each group had statistical significance.The GCS score decreased and the number of inflammatory cells increased.The GCS score was negatively correlated with the expression of miRNA-155,mortality,and poor prognosis.In summary,the expression of miRNA-155 in peripheral blood has a very significant relationship with the occurrence,prognosis and outcome of cerebral hemorrhage.
Keywords/Search Tags:Cerebral hemorrhage, MiRNA-155, Real-time quantitative PCR, GCS score, Bleeding amount
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