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Study On The Expression Of S100A8/A9 In Serum Of Patients With Acute Arteriosclerotic Cerebral Infarction

Posted on:2018-09-12Degree:MasterType:Thesis
Country:ChinaCandidate:Z D PuFull Text:PDF
GTID:2334330533465641Subject:Neurology
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1.Background and objective of the study: With the aging of population,the rapid growth of economy and the change of life style,cardiovascular disease,cerebrovascular disease and malignant tumor have constituted the three main causes of death.In recent years,studies have shown that cerebrovascular disease has gone beyond the cardiovascular disease to rank first in death of the population in China.Moreover,the number of death continues to grow every year.Acute cerebral infarction,as a common disease of the nervous system in acute cerebrovascular disease,is the third leading cause of mortality and disability rate around the world,making it a serious threat to life and health of the elderly.Moreover,its incidence rate shows an obvious upward trend.With the development of study on etiology of acute ischemic stroke,the etiology of ischemic stroke is divided into the following five types: large artery atherosclerosis(LAA),cardiogenic stroke(CS),penetrating artery disease(PAD),stroke of other etiologies(OE)and stroke of undetermined etiology(UE).The most common type is atherosclerotic cerebral infarction(Atherosclerotic cerebral infarction,ACI),namely,type LAA.The disease is mainly caused by carotid artery or intracranial artery stenosis,leading insufficient blood supply,and gives rise to ischemic necrosis of the brain as well as neurological dysfunction.Acute and chronic inflammation is the pathological basis of ACI vascular disease.The occurrence of ACI is a multi factor,multi-level integrated process.In addition to other risk factors for cerebral infarction,the medical community has come to realize that inflammatory response or chronic infectious disease is an independent risk factor foratherosclerotic cerebral infarction.After cerebral ischemia,signaling pathway mediated by inflammatory signal receptor plays an important role during the inflammatory cascade reaction.S100A8/A9,possessing a rich biological function,is a member of the S100 family of calcium binding proteins.It correlates highly with inflammation and is an important regulator of acute and chronic inflammation.In addition,it forms a stable heteromorphic two-mer complex,extends in space through its CTerminal-alpha helix,and finally forms tetramer in the form of non covalent bond.S100A8/A9,also known as MRP8/14,is derived from activated neutrophils,monocytes,macrophages,dendritic cells and vascular smooth muscle cells.From the functional point of view,there are two affinity Zn2+ binding sites in the subunit interface,which has the important function of promoting inflammation.S100A8/A9,possessing a wide range of intracellular and extracellular biological function,can be specifically secreted into inflammatory lesions and is the powerful inducer of neutrophil chemotaxis and adhesion.Highly correlated with inflammation,it plays a major role in all kinds of acute and chronic inflammatory diseases.For example,it was found that S100A8/A9 dimer concentration increased in acute coronary syndrome,heart fail,rheumatoid arthritis,inflammatory bowel disease and pulmonary disease.However,there are few reports about the expression and clinical research of S100A8/A9 in ACI disease.2.Research contents and methods Participants: 103 patients with AACI from internal neurology department of the twelfth people's Hospital of Guangzhou from September 2015 to February 2017.60 healthy people from our hospital physical examination center were selected as control group.All participants signed informed consent.The case group inclusion criteria: all cases were acute onset,not only with clear focal neurological symptoms and signs of damage but also diagnosed by the head CT(or MRI),and had excluded cerebral hemorrhage,cerebral embolism or other causes of cerebral infarction.Meanwhile,they are in line with the reviseddiagnostic criteria of the Fourth National Academic Conference on cerebrovascular disease.Two groups have excluded the following situation:(1)Other factors that may affect the relevant indicators,such as myocardial infarction,liver and renal dysfunction.(2)No use for the following drugs for nearly 2 weeks: lipid-lowering drugs(statins),lipoprotein associated phospholipase A2 inhibitors,anti-inflammatory drugs,immunosuppressive agents.(3)A history of infection within the last 1 month.(4)The head suffers trauma and has not been recovered or there is a head operation record in the recent past.We use all the cases in accordance with the Chinese stroke degree of clinical neural function defect scale to make neurological investigation.Then,we divide the patients into mild group(0 ~ 15),medium group(16 ~ 30),severe group(31 ~ 45),according to the level of consciousness and the severity of neurological impairment.The higher the score of nerve function is,the more serious the defect is.Full score is 45 points.Score personnel should be doctors who must be carried out professional training and possess rich clinical experience.Research program: We collect 2 tube 5ml fasting elbow venous blood of the control group in the early morning.Meanwhile,we check 2 tube 5ml elbow venous blood of ACI patients admitted to hospital emergency.Then,we place respectively one of two tubes in the two groups into common vacuum vessel for blood collection.After standing for 30 min at 4?,we centrifuge them at the speed of 4000r/min for 15 min and separate serum into EP tube.Finally,we keep them in the refrigerator at-80?.When collecting all the samples,we measure the S100A8/A9 concentration by enzyme-linked immunosorbent assay.We place the other blood of two tubes in the two groups into anticoagulation tube containing EDTA and stand at room temperature for half an hour.Then,we immediately centrifuge them at the speed of 3000r/min for 20 min at 4? and keep serum in the frozen tube.Finally,we keep them in the refrigerator at-80?.When collecting all the samples,we measure the hs-CRP concentration of unity by immunoturbidimetric assay.All data were processed by SPSS 16statistical software.3.Results It's 103 cases altogether,including 35 cases of mild group: S100A8/A9(2.62 ±1.22)ug/ml,hs-CRP(23.95±3.56)mg/l;46 patients of medium group:S100A8/A9(4.90±4.65)ug/ml,hs-CRP(25.23±2.34)mg/l;and 22 cases of severe group: S100A8/A9(5.85± 3.76)ug/ml,hs-CRP(26.33 ± 9.87)mg/l.All above were higher than those in the control group(60 cases):S100A8/A9(1.07±0.53)ug/ml,hs-CRP(3.29±1.09)mg/l.There is statistically significant difference between them(P<0.05).Comparison between the two subgroups:Compared with mild group,P<0.05,there is statistically significant difference between them;Compared with medium group,P<0.05,there is statistically significant difference between them? Linear correlation analysis:Spearman correlation analysis revealed that the levels of serum S100A8/A9 with every subgroup were positive correlated with hs-CRP?4.Conclusion In patients with acute atherosclerotic cerebral infarction,serum S100A8/A9 levels in peripheral blood are significantly increased,and the level has positive correlation with hs-CRP,which suggests that S100A8/A9 may be related to the development of the disease and become a new indicator of inflammation.S100A8 / A9 levels with the severity of the disease may exist a certain degree of positive correlation.
Keywords/Search Tags:atherosclerotic cerebral infarction, neutrophil, S100A8/A9, hs-CRP, Positive correlation
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