本文選題：胸腺肽α1 + 嚴(yán)重膿毒癥��； 參考：《南方醫(yī)科大學(xué)》2016年碩士論文

【摘要】：研究背景在美國,每年每10萬人中發(fā)生膿毒癥例數(shù)超過200例,發(fā)生嚴(yán)重膿毒癥的例數(shù)也高達(dá)50-95例,且膿毒癥發(fā)病率逐年增高,在過去的20年里,美國住院患者中,膿毒癥的發(fā)病率每年以8.7%的速度遞增。盡管人們一直致力于膿毒癥的預(yù)防與治療,嚴(yán)重膿毒癥的病死率仍高達(dá)20-50%,嚴(yán)重膿毒癥已成為重癥監(jiān)護(hù)病房中患者的主要死亡原因。起初人們認(rèn)為強(qiáng)烈的炎癥反應(yīng)是導(dǎo)致膿毒癥患者的主要死亡原因,然而,大量的針對(duì)早期炎癥介質(zhì)的目標(biāo)治療,如抗腫瘤壞死因子a抗體、白介素1受體抗體治療并沒有改善膿毒癥患者的臨床預(yù)后。目前,淋巴細(xì)胞凋亡和免疫抑制越來越多的被認(rèn)為在膿毒癥的發(fā)病機(jī)制中起到關(guān)鍵的作用,有膿毒癥動(dòng)物模型實(shí)驗(yàn)和臨床試驗(yàn)指出,阻止淋巴細(xì)胞凋亡和加強(qiáng)免疫功能可以改善受試者的預(yù)后。腫瘤壞死因子a被認(rèn)為是膿毒癥重要的促炎癥反應(yīng)介質(zhì)之一,但Docke et al指出,腫瘤壞死因子a分泌水平的增加表明單核細(xì)胞功能及抗微生物反應(yīng)能力的恢復(fù),體外脂多糖刺激后腫瘤壞死因子α的分泌量可以作為一個(gè)有效的指標(biāo)來評(píng)估膿毒癥患者的免疫狀態(tài)。Hall et al也指出體外刺激全血后引起腫瘤壞死因子α的分泌量可以作為一個(gè)有用的生物標(biāo)志物來監(jiān)測(cè)膿毒癥患者的免疫功能。胸腺肽α1是胸腺分泌的一種激素,最早于1972年由Goldstein等首次發(fā)現(xiàn)并對(duì)其特征進(jìn)行了描述。胸腺肽a1被認(rèn)為是一種免疫調(diào)節(jié)多肽,在臨床上已廣泛應(yīng)用于慢性乙型肝炎及丙型肝炎的免疫調(diào)理治療。胸腺肽α1在免疫系統(tǒng)中有很多生物學(xué)活性,如激活自然殺傷細(xì)胞,刺激T淋巴細(xì)胞的增殖、分化和成熟,阻止淋巴細(xì)胞凋亡。因此,作為一種免疫調(diào)節(jié)劑,胸腺肽α1可以用于膿毒癥的治療。有相關(guān)臨床研究發(fā)現(xiàn),胸腺肽α1治療嚴(yán)重膿毒癥可以取得有益的治療效果。然而,由于嚴(yán)重膿毒癥患者的異質(zhì)性,胸腺肽α1或許對(duì)有些患者有效,對(duì)有些患者療效不明顯,這些研究沒有指出哪些嚴(yán)重膿毒癥患者用胸腺肽α1治療更有效。本研究主要觀察胸腺肽α1對(duì)哪些嚴(yán)重膿毒癥患者的治療效果更好,及胸腺肽α1對(duì)嚴(yán)重膿毒癥患者APACHEⅡ評(píng)分、SOFA評(píng)分、淋巴細(xì)胞計(jì)數(shù)的影響,同時(shí)用脂多糖體外刺激嚴(yán)重膿毒癥患者的外周血單個(gè)核細(xì)胞后分泌的腫瘤壞死因子α的濃度,來評(píng)估胸腺肽α1對(duì)嚴(yán)重膿毒癥患者免疫功能的影響。研究目的1.探討胸腺肽α1對(duì)嚴(yán)重膿毒癥患者28天死亡率及生存時(shí)間的影響；2.探討胸腺肽α1對(duì)嚴(yán)重膿毒癥患者APACHEII評(píng)分、SOFA評(píng)分、淋巴細(xì)胞計(jì)數(shù)的影響；3.探討胸腺肽α1對(duì)嚴(yán)重膿毒癥患者免疫功能的影響。研究方法1.倫理學(xué)標(biāo)準(zhǔn)收集2013年1月至2014年12月住入我院重癥醫(yī)學(xué)科的嚴(yán)重膿毒癥患者為回顧性研究,統(tǒng)計(jì)數(shù)據(jù)時(shí)為匿名分析,故免簽知情同意書。用脂多糖體外刺激嚴(yán)重膿毒癥患者的外周血單個(gè)核細(xì)胞后分泌的腫瘤壞死因子α的濃度,來評(píng)估胸腺肽α1對(duì)嚴(yán)重膿毒癥患者免疫功能的影響,此體外實(shí)驗(yàn)抽取患者血液時(shí)均由患者或直系親屬簽署知情同意書。本研究符合醫(yī)學(xué)倫理學(xué)標(biāo)準(zhǔn),經(jīng)醫(yī)院倫理委員會(huì)批準(zhǔn),批準(zhǔn)號(hào)：2014一ZZYXK-003。2.研究對(duì)象收集2013年1月至2014年12月住入我院重癥醫(yī)學(xué)科,符合2001年國際膿毒癥定義會(huì)議制定的嚴(yán)重膿毒癥診斷標(biāo)準(zhǔn)的患者。排除標(biāo)準(zhǔn)：年齡小于18歲、妊娠期婦女、患有惡性腫瘤、自身免疫性疾病、血液系統(tǒng)疾病(如再生障礙性貧血、白血病等)、或在過去1個(gè)月內(nèi)使用過激素、免疫抑制劑或其他免疫刺激劑的患者,失訪的患者。最終,244例患者納入本研究。其中男169例,女75例,平均年齡(63.0±16.4)歲。引起嚴(yán)重膿毒癥的原發(fā)感染灶為：肺部感染183例,腹部感染32例,泌尿系感染11例,其他部位感染18例。體外實(shí)驗(yàn)選擇2015年1月診斷為嚴(yán)重膿毒癥且不符合上述排除標(biāo)準(zhǔn)的患者12例進(jìn)行抽血。3.數(shù)據(jù)收集通過瀏覽患者的臨床病歷資料,收集患者的性別、年齡、引起嚴(yán)重膿毒癥的原發(fā)感染灶、APACHEII評(píng)分、SOFA評(píng)分、淋巴細(xì)胞計(jì)數(shù)和預(yù)后等指標(biāo)(或者電話聯(lián)系患者家屬以獲取患者的預(yù)后信息)。(以上檢測(cè)指標(biāo)均有我院檢驗(yàn)科及重癥醫(yī)學(xué)科完成)。4.分組(1)244例患者中,根據(jù)患者確診嚴(yán)重膿毒癥后是否給予胸腺肽α1治療分為胸腺肽α1組和非胸腺肽α1組,非胸腺肽α1組根據(jù)2008年國際嚴(yán)重膿毒癥診療指南采用常規(guī)治療方案,胸腺肽α1組在常規(guī)治療基礎(chǔ)上聯(lián)合應(yīng)用胸腺肽α1皮下注射1.6mg,每12小時(shí)1次,連用7天。(2)胸腺肽α1組和非胸腺肽α1組患者根據(jù)確診嚴(yán)重膿毒癥后第1天淋巴細(xì)胞計(jì)數(shù)分為三個(gè)亞組：≥1.00×109/L亞組,0.50-1.00×109/L亞組和≤0.50×109/L亞組。5.體外實(shí)驗(yàn)方案(1)嚴(yán)重膿毒癥患者的外周血單個(gè)核細(xì)胞分離分別抽取12例嚴(yán)重膿毒癥患者血液4m1于抗凝真空采血管中,加等體積磷酸緩沖鹽溶液稀釋,另加3m1人Ficoll分離液至離心管中,然后將稀釋后的血液疊加到Ficoll分離液上層。將離心管在水平離心機(jī)中離心,2000轉(zhuǎn)/min離心30min,取出離心管,管內(nèi)液體分為3層,用吸管取出中層含有外周血單個(gè)核細(xì)胞的Ficoll液,放入另一離心管中,再加等體積磷酸緩沖鹽溶液稀釋后再離心,1000轉(zhuǎn)/min離心10min,棄去含有血小板的上層液,離心管中沉淀物即為外周血單個(gè)核細(xì)胞。(2)胸腺肽α1對(duì)脂多糖刺激外周血單個(gè)核細(xì)胞分泌腫瘤壞死因子α的影響將含有10%胎牛血清的RPMI1640培養(yǎng)基平均分成3組：對(duì)照組、脂多糖組和脂多糖+胸腺肽a1組,在脂多糖+胸腺肽α1組中加入胸腺肽a1使其濃度達(dá)到200μg/ml,對(duì)照組和脂多糖組分別加入等體積磷酸緩沖鹽溶液,每一組培養(yǎng)基中均加入外周血單個(gè)核細(xì)胞使其濃度達(dá)到106個(gè)細(xì)胞/ml,然后將3組培養(yǎng)基均置于37℃5% CO2培養(yǎng)箱中培養(yǎng)8小時(shí)。結(jié)束后,脂多糖組和脂多糖+胸腺肽a1組分別加入含脂多糖的磷酸緩沖鹽溶液,使脂多糖終濃度為10μg/ml,對(duì)照組加入等體積磷酸緩沖鹽溶液,繼續(xù)培養(yǎng)6小時(shí)。結(jié)束后,分別取各組細(xì)胞培養(yǎng)上清液,用ELISA試劑盒檢測(cè)腫瘤壞死因子α的濃度。6.統(tǒng)計(jì)方法全部數(shù)據(jù)用SPSS 19.0進(jìn)行統(tǒng)計(jì)分析,對(duì)計(jì)量資料進(jìn)行正態(tài)性檢驗(yàn),成正態(tài)分布者用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,采用兩獨(dú)立樣本均數(shù)的t檢驗(yàn)；呈偏態(tài)分布者用中位數(shù)與四分位數(shù)表示[M(QR)],采用兩獨(dú)立樣本的mann-whitney U秩和檢驗(yàn)；分類變量用頻率表示,采用x2檢驗(yàn)；患者的生存時(shí)間用Kaplan-Meier分析并使用log-rank進(jìn)行檢驗(yàn)；腫瘤壞死因子α的濃度比較采用單因素方差分析,組間比較采用LSD檢驗(yàn)。以上檢驗(yàn)均以P0.05為差異具有統(tǒng)計(jì)學(xué)意義。研究結(jié)果1.一般資料244例患者納入本研究,其中胸腺肽a1組127例,非胸腺肽α1組117例患者,胸腺肽a1組與非胸腺肽α1組兩組患者的性別、年齡比較,差異均無統(tǒng)計(jì)學(xué)意義(均P0.05)、確診嚴(yán)重膿毒癥后第1天雖然胸腺肽a1組患者APACHEII評(píng)分、SOFA評(píng)分高于非胸腺肽α1組、淋巴細(xì)胞計(jì)數(shù)低于非胸腺肽a1組,但兩組比較,差異也均無統(tǒng)計(jì)學(xué)意義(均P0.05),根據(jù)淋巴細(xì)胞計(jì)數(shù)分層后,兩組中各亞組間比較,以上指標(biāo)差異也均無統(tǒng)計(jì)學(xué)意義(均P0.05)。2.患者預(yù)后比較胸腺肽a1組與非胸腺肽α1組患者28天死亡率分別為42.5%、50.4%,兩組間比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05),兩組中淋巴細(xì)胞計(jì)數(shù)≥1.00×10札亞組和0.50-1.00×109/L亞組患者的28天死亡率比較,差異也均無統(tǒng)計(jì)學(xué)意義(均P0.05),但在淋巴細(xì)胞計(jì)數(shù)≤0.50×109/L亞組,胸腺肽α1組患者28天死亡率顯著低于非胸腺肽a1組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。3.患者生存時(shí)間比較胸腺肽a1組與非胸腺肽a1組患者生存時(shí)間比較,差異無統(tǒng)計(jì)學(xué)意義(log-rank檢驗(yàn),P0.05),兩組中淋巴細(xì)胞計(jì)數(shù)≥1.00×109/L亞組和0.50-1.00×109/L亞組患者生存時(shí)間比較,差異也均無統(tǒng)計(jì)學(xué)意義(log-rank檢驗(yàn),均P0.05),但在淋巴細(xì)胞計(jì)數(shù)≤0.50×109幾亞組,胸腺肽α1組患者生存時(shí)間顯著長于非胸腺肽α1組,差異有統(tǒng)計(jì)學(xué)意義(log-rank檢驗(yàn),P0.05)。4. 嚴(yán)重膿毒癥第7天與第1天各指標(biāo)動(dòng)態(tài)變化值胸腺肽α1組與非胸腺肽α1組比較胸腺肽α1組與非胸腺肽α1組APACHEII評(píng)分在診斷嚴(yán)重膿毒癥后第7天均顯著低于第1天(均P0.05),胸腺肽α1組比非胸腺肽α1組降低更顯著(P0.05),胸腺肽a1組SOFA評(píng)分在診斷嚴(yán)重膿毒癥后第7天顯著低于第1天(P0.05),非胸腺肽α1組SOFA評(píng)分在診斷嚴(yán)重膿毒癥第7天雖低于第1天,但差異無統(tǒng)計(jì)學(xué)意義(P0.05),胸腺肽α1組與非胸腺肽α1組SOFA評(píng)分變化值比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05),胸腺肽α1組與非胸腺肽α1組淋巴細(xì)胞計(jì)數(shù)在診斷嚴(yán)重膿毒癥后第7天均顯著高于第1天(均P0.05),但胸腺肽α1組比非胸腺肽α1組變化更顯著(P0.05)。5.體外實(shí)驗(yàn)結(jié)果對(duì)照組、脂多糖組和脂多糖+胸腺肽al組三組中腫瘤壞死因子α的濃度比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05),脂多糖+胸腺肽α1組腫瘤壞死因子α的濃度顯著高于對(duì)照組與脂多糖組,差異均有統(tǒng)計(jì)學(xué)意義(均P0.05)。脂多糖組腫瘤壞死因子α的濃度也顯著高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。研究結(jié)論1.胸腺肽αl可以顯著降低淋巴細(xì)胞計(jì)數(shù)≤0.50×109/L的嚴(yán)重膿毒癥患者的28天死亡率,延長患者的生存時(shí)間；2.胸腺肽α1能夠顯著降低嚴(yán)重膿毒癥患者的APACHEII評(píng)分、SOFA評(píng)分,提高患者的淋巴細(xì)胞計(jì)數(shù),改善患者的病情；3.胸腺肽α1能夠顯著改善嚴(yán)重膿毒癥患者的免疫功能。
[Abstract]:In the United States, in the United States, more than 200 cases of sepsis occur in more than 200 cases per 100 thousand people each year. The number of cases of severe sepsis is also up to 50-95, and the incidence of sepsis increases year by year. In the past 20 years, the incidence of sepsis increases at a rate of 8.7% per year in American inpatients, although people have been committed to the prevention and prevention of sepsis. The fatality rate of severe sepsis is still as high as 20-50%, and severe sepsis has become the main cause of death in the intensive care unit. At first it was believed that the strong inflammatory response was the main cause of death in patients with sepsis. However, a large number of targets for early inflammatory mediations, such as anti tumor necrosis factor A antibodies, were found to be the main cause of death. The treatment of the 1 receptor antibody does not improve the clinical prognosis of patients with sepsis. At present, the increasing number of lymphocyte apoptosis and immunosuppression is considered to play a key role in the pathogenesis of sepsis. The experimental and clinical trials of sepsis animal model and clinical trials point out that the prevention of apoptosis and the strengthening of immune function can improve the disease. The tumor necrosis factor A is considered to be one of the important proinflammatory mediators of sepsis, but Docke et al points out that the increase in the secretion of tumor necrosis factor A indicates the recovery of monocyte function and the ability to resist microbial reaction, and the secretion of tumor necrosis factor alpha after lipopolysaccharide stimulation in vitro can be an effective one. The index to evaluate the immune state of patients with sepsis.Hall et al also points out that the secretion of TNF - alpha induced by in vitro stimulation of whole blood can be used as a useful biomarker to monitor the immune function of patients with sepsis. Thymosin alpha 1 is a hormone secreted in the thymus, first found in 1972 by Goldstein and so on. Its characteristics are described. Thymosin A1 is considered as an immunomodulatory polypeptide that has been widely used in the immunomodulatory treatment of chronic hepatitis B and hepatitis C. Thymosin alpha 1 has many biological activities in the immune system, such as activating natural killer cells, stimulating the proliferation, differentiation and maturation of T lymphocytes, and preventing lymphatic lymph nodes. Apoptosis. Therefore, as an immunomodulator, thymosin alpha 1 can be used in the treatment of sepsis. Related clinical studies have found that thymosin alpha 1 in the treatment of severe sepsis can achieve beneficial effects. However, due to the heterogeneity of patients with severe sepsis, thymosin alpha 1 may be effective in some patients, and some patients are not effective. Obviously, these studies did not point out which patients with severe sepsis were more effective with thymosin alpha 1. This study was mainly to observe the effect of thymosin alpha 1 on patients with severe sepsis, and the effect of thymosin alpha 1 on APACHE II score, SOFA score, lymphocytic count, and in vitro stimulation of lipopolysaccharide. The concentration of tumor necrosis factor alpha secreted by peripheral blood mononuclear cells in patients with severe sepsis to assess the effect of thymosin alpha 1 on the immune function of patients with severe sepsis. Purpose 1. to investigate the effect of thymosin alpha 1 on 28 day mortality and survival time in patients with severe sepsis; 2. to explore A of thymosin alpha 1 for patients with severe sepsis. The effect of PACHEII score, SOFA score and lymphocyte count; 3. to explore the effect of thymosin alpha 1 on the immune function of patients with severe sepsis. Methods 1. ethics standards were collected from January 2013 to December 2014 for severe sepsis in the Department of intensive medicine of our hospital for a retrospective study. Agreement. The concentration of TNF - alpha secreted by the peripheral blood mononuclear cells of patients with severe sepsis in vitro by using lipopolysaccharide to evaluate the effect of thymosin alpha 1 on the immune function of patients with severe sepsis. Ethical standards, approved by the hospital ethics committee, approval number: 2014 one ZZYXK-003.2. research subjects were collected from January 2013 to December 2014 in the Department of severe medicine in our hospital, which conformed to patients with severe sepsis diagnosed by the 2001 International Sepsis definition conference. Exclusion criteria: age less than 18 years, pregnant women, and malignant Tumors, autoimmune diseases, hematological diseases (such as aplastic anemia, leukemia, etc.), or patients who have used hormones, immunosuppressive agents or other immunostimulants within the past 1 months, and in 244 patients, including 169 men and 75 women, with an average age of (63 + 16.4) years of age. The primary infection was: 183 cases of pulmonary infection, 32 cases of abdominal infection, 11 cases of urinary tract infection, and 18 cases of other infections. In vitro, 12 cases of severe sepsis diagnosed as severe sepsis in January 2015 and 12 patients who did not meet the above exclusion criteria were collected by scanning the patient's clinical records to collect the sex and age of the patients. Primary infection foci of severe sepsis, APACHEII score, SOFA score, lymphocyte count and prognosis (or telephone contact with the patient's family to obtain the patient's prognosis information). (all of the above tests were performed in the Department of laboratory and the Department of critical medicine) in the.4. group (1) in 244 patients, after the patient was diagnosed with severe sepsis. The treatment of thymosin alpha 1 was divided into groups of thymosin alpha 1 and non thymosin alpha 1 group. Non thymosin alpha 1 group was treated with conventional therapy according to the 2008 International severe sepsis guidelines. The thymosin alpha 1 group was combined with thymosin alpha 1 subcutaneous injection of 1.6mg, 1 times per 12 small, and 7 days. (2) thymosin alpha 1 and non thymus. The patients in the 1 group of peptide alpha 1 were divided into three subgroups on the first day after diagnosis of severe sepsis: 1 x 109/L subgroup, 0.50-1.00 x 109/L subgroup and < 0.50 x 109/L subgroup.5. extracorporeal experimental scheme (1) separation of peripheral blood mononuclear cells from severe sepsis patients, 12 cases of severe sepsis patients' blood 4m1 in anticoagulant vacuum In the blood vessels, an equal volume of phosphate buffer solution was diluted and 3M1 human Ficoll was added to the centrifuge tube, and then the diluted blood was superimposed on the upper layer of the Ficoll separation solution. Centrifuge tube was centrifuged in a horizontal centrifuge and 2000 /min centrifuged 30min, the centrifuge tube was removed, the liquid body in the tube was divided into 3 layers, and the middle layer of peripheral blood was taken out with a sucker to contain peripheral blood single. The Ficoll solution of the nuclear cells was placed in another centrifuge tube and then diluted with an equal volume of phosphoric acid buffer solution and then centrifuged. 1000 turns /min to centrifuge 10min and discard the superfluid containing platelets. The precipitates in the centrifuge tube were peripheral blood mononuclear cells. (2) thymosin alpha 1 secreted TNF - alpha on lipopolysaccharide stimulated peripheral blood mononuclear cells The RPMI1640 medium containing 10% fetal bovine serum was divided into 3 groups: the control group, the lipopolysaccharide group and the lipopolysaccharide + thymosin A1 group, the concentration of thymosin A1 in the lipopolysaccharide + thymosin alpha 1 group was 200 g/ml, the control group and the lipopolysaccharide group were added to the constant volume phosphoric acid salt solution respectively, and each group was added to the periphery. The concentration of blood mononuclear cells reached 106 cells /ml, and then the 3 groups were incubated in the incubator of 37 centigrade 5% CO2 for 8 hours. After the end, the lipopolysaccharide group and the lipopolysaccharide + thymosin A1 group were added to the phosphate buffer solution containing lipopolysaccharide, and the final concentration of lipopolysaccharide was 10 g/ ml, and the control group was added to the equal volume phosphate buffer solution. After 6 hours, the cell culture supernatant was taken and the concentration of TNF - A was detected by ELISA kit. All data were analyzed by SPSS 19, and the normal distribution of the data was tested. The normal distribution was expressed with the average number of.6. s (x + s), and the t test of two independent samples was used. [M (QR) was expressed in the median and four digits, and the Mann-Whitney U rank sum test of the two independent samples was used. The classification variable was expressed by the frequency, and the x2 test was used. The patient's survival time was analyzed by Kaplan-Meier and tested with log-rank; the concentration of the tumor necrosis factor alpha was compared with the single factor variance analysis. LSD test was used between groups. The above tests were statistically significant with P0.05. 1. general data of the study were included in the study, including 127 cases of thymosin A1 group, 117 non thymosin alpha 1 group, and two groups of thymosin A1 and non thymosin alpha 1 group, the difference was not statistically significant (P0. 05), first days after severe sepsis, although the APACHEII score of the thymosin A1 group was higher than the non thymosin alpha 1 group, the lymphocyte count was lower than the non thymosin A1 group, but the difference was also not statistically significant (all P0.05). After the lymphocyte count sublayer, the difference of the above indexes between the two groups was also no more. Statistically significant (P0.05).2. patients' prognosis compared with thymosin A1 group and non thymosin alpha 1 group, the 28 day mortality rate was 42.5%, 50.4%, the difference between the two groups was not statistically significant (P0.05), the two group of lymphocyte count > 1 * 10 Zart group and 0.50-1.00 x 109/L subgroup of the 28 day mortality compared, the difference was also not statistically significant Meaning (all P0.05), but in the lymphocyte count less than 0.50 x 109/L subgroup, the mortality of 28 days in the group of thymosin alpha 1 was significantly lower than the non thymosin A1 group, the difference was statistically significant (P0.05) the survival time of the.3. patients compared with the thymosin A1 group and the non thymosin A1 group, the difference was not statistically significant (log-rank test, P0.05), two groups. The survival time of the lymphocyte count > 1 x 109/L subgroup and the 0.50-1.00 x 109/L subgroup was not statistically significant (log-rank test, P0.05), but in the lymphocyte count < 0.50 x 109 subgroups, the survival time of the thymosin alpha 1 group was significantly longer than that of the non thymic peptide alpha 1 group, the difference was statistically significant (log-rank test, P0.05). .4., seventh days and first days of severe sepsis, the dynamic change values of thymosin alpha 1 and non thymosin alpha 1 were compared with the APACHEII score of thymosin alpha 1 and non thymosin alpha 1 in the diagnosis of severe sepsis significantly lower than first days (all P0.05), thymosin a 1 group was more significantly lower than the non thymic peptide a 1 group (P0.05), thymosin A1 group SOFA The score was significantly lower than first days after the diagnosis of severe sepsis (P0.05). The SOFA score of the non thymosin alpha 1 group was lower than first days in the diagnosis of severe sepsis, but the difference was not statistically significant (P0.05). The difference between the thymosin alpha 1 group and the non thymosin alpha 1 group was not statistically significant (P0.05), the thymosin a 1 group and the non thymus gland were not significant (P0.05). The lymphocyte count in the 1 group of peptide alpha 1 was significantly higher than first days after the diagnosis of severe sepsis (all P0.05), but the change of thymosin alpha 1 was more significant than that of non thymosin alpha 1 group (P0.05) in the control group of.5. in vitro, and the difference was statistically significant between the lipopolysaccharide group and the group three of the lipopolysaccharide + thymosin al Group (P0.0 5) the concentration of TNF - alpha in the lipopolysaccharide + thymosin alpha 1 group was significantly higher than that in the control group and the lipopolysaccharide group. The difference was statistically significant (P0.05). The concentration of TNF - alpha in lipopolysaccharide group was also significantly higher than that in the control group (P0.05). The study concluded that 1. thymosin alpha l could significantly reduce the lymphocyte count less than 0.50 The 28 day mortality of patients with severe sepsis by X 109/L, prolonging the patient's survival time, and 2. thymosin alpha 1 can significantly reduce the APACHEII score of severe sepsis, SOFA score, increase the patient's lymphocyte count, improve the patient's condition, and 3. thymosin alpha 1 can significantly improve the immune function of patients with severe sepsis.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R459.7

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