本文選題：基質(zhì)細(xì)胞衍生因子-1α + CXCR4��； 參考：《河北醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的：乙型肝炎病毒（hepatitis B virus, HBV）相關(guān)慢加急性肝衰竭（acute-on-chronic liver failure,ACLF）是在慢性乙型肝病基礎(chǔ)上發(fā)生的嚴(yán)重肝功能損害，出現(xiàn)以黃疸、肝性腦病和腹水等為主要表現(xiàn)的臨床綜合征，其發(fā)病急，病情兇險(xiǎn)，，病死率高且治療方法有限。來自骨髓的干細(xì)胞可遷移到損傷肝臟，通過分化為肝細(xì)胞修復(fù)損傷肝組織。本研究通過觀察HBV相關(guān)ACLF患者肝組織及血清中基質(zhì)細(xì)胞衍生因子-1α (stromal cellderived factor-1α，SDF-lα)的水平及肝組織Ki-67的表達(dá)，同時(shí)比較不同預(yù)后ACLF患者血清SDF-1α水平，初步探討SDF-1α在ACLF患者肝干細(xì)胞歸巢中的作用。 方法：收集2011年3月至2012年11月于河北醫(yī)科大學(xué)第三醫(yī)院和石家莊市第五醫(yī)院住院患者，共57例，其中HBV相關(guān)ACLF患者30例，慢性乙型肝炎(chronic hepatitis B CHB)患者27例，另外選取同期河北醫(yī)科大學(xué)第三醫(yī)院健康體檢者20例作為健康對(duì)照組。另外收集接受肝移植的ACLF患者及肝組織活檢的CHB患者肝組織各10例，正常供體肝組織8例。HBV相關(guān)ACLF和CHB的診斷分別符合中華醫(yī)學(xué)會(huì)感染病學(xué)分會(huì)及肝病學(xué)分會(huì)聯(lián)合制定的2006年版《肝衰竭診療指南》和2010年版《慢性乙型肝炎防治指南》中的診斷標(biāo)準(zhǔn)。檢測(cè)患者血清生化指標(biāo)、凝血功能及HBV DNA載量，應(yīng)用實(shí)時(shí)熒光定量PCR檢測(cè)肝組織SDF-1α mRNA的表達(dá)，免疫組織化學(xué)檢測(cè)肝組織內(nèi)SDF-1α及Ki-67蛋白的表達(dá)，酶聯(lián)免疫吸附法檢測(cè)血清SDF-1α的水平。比較血清SDF-1α水平在ACLF患者存活組和死亡組間的差異，并與HBV DNA載量及終末期肝病模型（model of end-stage liver disease, MELD）評(píng)分進(jìn)行相關(guān)性分析。 結(jié)果： 1ACLF組、CHB組及健康對(duì)照組人口學(xué)及臨床特點(diǎn) 各組患者的年齡和性別比例具有可比性。ACLF組患者血清丙氨酸氨基轉(zhuǎn)移酶（alanine aminotransferase,ALT）、天冬氨酸氨基轉(zhuǎn)移酶（aspartateaminotransferase, AST）、總膽紅素（total bilirubin, TBIL）、直接膽紅素（direct bilirubin, DBIL）、國(guó)際標(biāo)準(zhǔn)化比值（international normalized ratio,INR）水平明顯高于CHB組及健康對(duì)照組（P均0.01），ACLF組和CHB組HBV DNA載量無明顯差異（P0.05）。 2ACLF患者肝組織SDF-1α mRNA表達(dá)增多 共8例HBV相關(guān)ACLF患者、10例CHB患者和8例健康對(duì)照者接受SDF-1α mRNA表達(dá)檢測(cè)。ACLF組肝組織SDF-1α mRNA表達(dá)（3.4±1.02）顯著高于CHB組（2.16±1.19）和健康對(duì)照組（1.00），差異均具有統(tǒng)計(jì)學(xué)意義（P0.05或P0.01）。同樣，CHB組與健康對(duì)照組比較，差異也具有統(tǒng)計(jì)學(xué)意義（P0.05）。 3ACLF患者肝組織SDF-1α及Ki-67蛋白表達(dá)增多 共10例HBV相關(guān)ACLF患者、10例CHB患者和6例健康對(duì)照者接受肝組織SDF-1α及Ki67表達(dá)檢測(cè)。ACLF患者匯管區(qū)膽管上皮細(xì)胞和肝臟干細(xì)胞高表達(dá)SDF-1α，且伴明顯的小管樣反應(yīng)，而健康對(duì)照者僅在膽管上皮細(xì)胞表達(dá)SDF-1α，其陽性染色平均吸光度值分別為（0.345±0.095）、（0.178±0.116）、（0.051±0.022）。ACLF患者匯管區(qū)內(nèi)可見大量的Ki-67+細(xì)胞，肝實(shí)質(zhì)內(nèi)亦可見散在分布的陽性細(xì)胞，其陽性細(xì)胞數(shù)依次為（171.2±52.8）、（42.4±17.8）和（4.7±1.9）/高倍視野，各組間比較差異均有統(tǒng)計(jì)學(xué)意義（P均0.01），其中以ACLF組為最高，健康對(duì)照組最低。 4ACLF患者血清SDF-1α水平降低 共30例HBV相關(guān)ACLF患者、27例CHB患者和20例健康對(duì)照者接受血清SDF-1α水平檢測(cè)。ACLF組血清SDF-1α水平（1717.33±458.07pg/ml）顯著低于CHB組（2638.96±574.04pg/ml）及健康對(duì)照組（2378.20±660.09pg/ml）（P均0.01）。而CHB組與健康對(duì)照組相比，差別無統(tǒng)計(jì)學(xué)意義(P0.05)。 5不同預(yù)后ACLF患者血清SDF-1α水平變化 共30例不同預(yù)后的HBV相關(guān)ACLF患者接受血清SDF-1α水平檢測(cè)。根據(jù)患者第28天的生存狀況，分為存活組（11例）和死亡組（19例）。存活組患者入院時(shí)血清SDF-1α水平（1497.69±408.55pg/ml）低于死亡組患者（1844.50±445.84pg/ml），兩組間比較差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。 6ACLF患者血清SDF-1α水平與HBV DNA及MELD評(píng)分的相關(guān)性 ACLF患者血清SDF-1α水平與HBV DNA載量（r=0.21, P=0.27）及MELD評(píng)分（r=0.17, P=0.38）無相關(guān)性。 結(jié)論： 1HBV相關(guān)ACLF患者肝組織內(nèi)存在肝干細(xì)胞再生。 2HBV相關(guān)ACLF患者肝組織內(nèi)SDF-1α表達(dá)較CHB患者及正常對(duì)照組明顯增多，但外周血中SDF-1α水平卻明顯降低，肝組織與外周血之間SDF-1α由高到低的濃度梯度可能是促進(jìn)干細(xì)胞歸巢至損傷肝臟的機(jī)制之一。 3外周血中低水平SDF-1α可能更有利于干細(xì)胞的歸巢，因此其水平較低可能預(yù)示患者短期預(yù)后較好。
[Abstract]:Objective: the hepatitis B virus (hepatitis B virus, HBV) associated acute liver failure (acute-on-chronic liver failure, ACLF) is a severe liver function damage based on chronic hepatitis B, which is characterized by jaundice, hepatic encephalopathy and ascites, which are characterized by acute, acute, dangerous, high mortality and treatment. The stem cells from the bone marrow can migrate to the injured liver and repair the liver tissue by differentiating into hepatocytes. This study observed the level of the matrix derived factor -1 alpha (stromal cellderived factor-1 alpha, SDF-l a) in the liver tissue and serum of the HBV related ACLF patients and the expression of Ki-67 in the liver tissue, and compared the different preconditioning. The level of serum SDF-1 alpha in post ACLF patients was preliminarily explored to investigate the role of SDF-1 alpha in the homing of hepatic stem cells in ACLF patients.
Methods: 57 cases were collected from March 2011 to November 2012 in Third Hospital of Hebei Medical University and fifth hospital in Shijiazhuang. Among them, 30 cases of HBV related ACLF patients, 27 cases of chronic hepatitis B (chronic hepatitis B CHB), and 20 healthy controls in Third Hospital of Hebei Medical University in the same period were selected as the healthy control group. In addition, 10 patients with ACLF and CHB patients with liver biopsy were collected, and 8 cases of.HBV related ACLF and CHB in normal donor liver tissues were diagnosed respectively in accordance with the 2006 edition of the association of infectious diseases and Hepatology branch of the Chinese Medical Association, the guide for the diagnosis and treatment of liver failure, and the 2010 edition of the guide for the prevention and treatment of chronic hepatitis B, respectively. The serum biochemical indexes, blood coagulation function and HBV DNA load were detected, the expression of SDF-1 alpha mRNA in liver tissue was detected by real-time fluorescence quantitative PCR, the expression of SDF-1 alpha and Ki-67 protein in liver tissue was detected by immunohistochemistry, and the level of serum SDF-1 a was detected by enzyme linked immunosorbent assay. The level of serum SDF-1 alpha was compared with those of ACLF patients. The difference between the survival group and the death group was correlated with the HBV DNA load and the model of end-stage liver disease (MELD) score.
Result錛

本文編號(hào)：1780950