肝细胞生长因子的激活诱导肝星状细胞凋亡

目的 探讨大鼠骨髓间充质干细胞(BMSCs)与肝星状细胞(HSCs)共培养体系中肝细胞生长因子激活因子(HGFA)激活肝细胞生长因子(HGF)后对HSCs凋亡的影响.方法 用半透膜建立上下双层细胞共培养体系,各组培养24h、48 h及72h后,倒置相差显微镜观察细胞形态学变化；流式细胞仪检测BMSCs表面抗原及HSCs凋亡率；四甲基偶氮唑盐法检测HSCs增殖率；免疫组织化学法检测HSCs中α-平滑肌肌动蛋白表达；免疫荧光及组织化学染色法检测HGF的激活形式(即HGF-α链)；酶联免疫吸附法检测HGF及HGFA浓度.计量资料采用单因素方差分析,组间均数的比较采用q检验. 结果 不同浓度HGF在各时段对HSCs无增殖抑制作用(P＞0.05),差异无统计学意义;HGFA在各时段对HSCs有明显增殖抑制作用,且呈浓度依赖性,在24h HGFA浓度为70 ng/ml时抑制作用为(0.26±0.00),较对照组的(0.13±0.04),明显增加,差异有统计学意义(P＜0.05);72h实验组HGF-α链相对表达量37.24±1.03低于HGFA干预组的40.44±0.77,差异有统计学意义(P＜ 0.05)；两者在各时段与对照组比较,差异均有统计学意义(P＜ 0.01).实验组HSCs凋亡率在72h为40.77％±1.16％,均较HGFA干预组的33.35％±2.04高,差异有统计学意义(P＜ 0.05)；两者在各时段与对照组比较,差异有统计学意义(P＜0.05).实验组及HGFA干预组中HGF浓度的降低呈时间依赖性,较HSCs空白对照组低；实验组HGFA的浓度在各时段均较对照组高.结论 BMSCs与HSCs共培养后促进HGFA的分泌,并激活HGF使其发挥促HSCs凋亡的作用.     

肝细胞生长因子研究进展

肝细胞坏死性肝炎的预后取决于肝细胞坏死程度和再生能力。70年代学者们集中探索体液因素对肝细胞再生的影响,并分别在血液和肝脏中都发现有促使和抑制肝细胞分裂繁殖的因子存在,这些因子的变化对肝细胞再生起着重要的作用。已陆续发现下述因子有促使肝细胞分裂作用:表皮生长因子     

肝细胞生长因子和器官纤维化

1984年，Nakamura等从部分肝切除大鼠的血清中分离出一种能刺激原代培养的肝细胞生长的因子，并将它命名为肝细胞生长因子（hepatocyte growth factor，HGF）。HGF能通过促进上皮细胞增殖、抑制上皮细胞凋亡及促进胶原降解、抑制胶原合成，参与肝、肾、心、肺等多种器官的结构重建，起器官保护作用，是少数能阻止纤维化的生长因子之一。     

肝细胞生长因子及其受体信号系统与肝细胞癌转移研究进展

肝细胞生长因子(HGF)是一种很强的刺激肝细胞增殖的丝裂原。HGF的单一受体c-Met是一跨膜蛋白，由原癌基因c-met编码。HGF激活c-Met，导致ras／致分裂素激活蛋白(MAP)激酶、磷脂酰肌醇、3-激酶／蛋白激酶B等信号转导途径的级联激活，细胞发生一系列生物学效应，如分散、细胞运动、侵袭、细胞迁移以及最终转移等。     

肝细胞生长因子在一些疾病中的变化及意义

肝细胞牛长因子具有多种作用,本文对其近年来在呼吸系统、循环系统、消化系统、泌尿系统等一些疾病发病中的作用及其意义作一综述。     

肝细胞生长因子受体

肝细胞生长因子（ＨＧＦ）是一种具有多样生物学作用的蛋白质生长因子，近年已广泛地应用于肝脏疾病的治疗实践中。经实验研究证实，ｃ－ｍｅｔ原癌基因编码蛋白为ＨＧＦ的特异性细胞膜受体。ｃ－ｍｅｔ是１９８４年Ｃｏｏｐｅｒ等从ＮＩＨ３Ｔ３细胞中克隆出的一种原癌基因。１９８７年Ｐａｒｋ等报道了ｃ－ｍｅｔｃＤＮＡ序列，并确定ｃ－ｍｅｔ属于酪氨酸激酶家族。一、ｃ－ｍｅｔ的结构与功能ｃ－ｍｅｔ定位于人类第７对染色体（７ｑ３．１－３４），ＨＧＦ为（７ｑ１１．２－２１）。ｃ－ｍｅｔ在机体内分布广泛，主要存在于上皮细胞中…     

肝细胞生长因子及其受体与胃癌

肝细胞生长因子(HGF)是一种多功能的细胞因子,原癌基因c-met编码的蛋白c-Met是HGF的主要受体,HGF与上皮或内皮细胞上的c-Met结合,导致细胞分裂或分化增加,细胞分离,运动能力增强,细胞连接消失。近年研究表明,HGF可影响肿瘤的生长、侵袭和肿瘤新生血管形成,HGF/c-Met与胃癌的发生、发展、转移及预后有着密切的关系。     

肝细胞生长因子的研究进展

肝细胞生长因子(Hepatocyte growth factor, HGF)最初是从大鼠血浆和血小板中分离得到的一种分泌型肝素亲和糖蛋白,又称为扩散因子(scatter factor, SF)。现已知,HGF由间质细胞产生,通过旁分泌方式作用于邻近细胞,与细胞表面的受体c-Met结合并激活该受体的酪氨酸激酶活性,从而促进包括肝细胞、上皮细胞、内皮细胞、黑色素细胞、造血细胞等     

肝细胞生长因子与肝细胞再生

肝脏是具有极强再生能力的器官。自Ｈｉｇｇｉｎｓ和Ａｎｄｅｒ－ｓｏｎ报道大鼠部分肝切除术后肝细胞迅速再生实验以来,学者们开展了众多关于肝细胞再生机制的研究。目前,就肝细胞再生启动与终止的机制尚未最终明确。肝细胞增生的过程是通过超乎想象的复杂的调控实现的。肝细胞增生大体可分为３个阶段①增殖启动过程（Ｇ０～Ｇ１期）,相关因子有ＩＬ－１,ＩＬ－６和ＴＮＦ－α;＠增殖促进调节过程（Ｇ１～Ｓ期）,相关因子有肝细胞生长因子（ＨＧＦ）,表皮生长因子（ＥＧＦ）／转化生长因子α（ＴＧＦα）等;③增殖停止过程（Ｇ１～…     

外源性肝细胞生长因子抗肝细胞凋亡机制的研究

目的通过小鼠尾静脉高压注射的方法在肝细胞中建立持续、高效表达外源性肝细胞生长因子(HGF)的体系,探讨其在肝细胞凋亡中的作用机制。方法通过尾部静脉注射pCMV-HGF质粒,检测肝组织中HGF表达的高峰。实验动物分为模型组、pcDNA3保护组、pCMV-HGF质粒保护组和生理盐水对照组,Western blot检测tBid、细胞色素C在各组肝细胞质及线粒体中的表达情况。结果在小鼠尾静脉快速大量注射质粒4h后肝脏中即有外源性HGF表达,8h达高峰。D-GalN/LPS可诱导明显的细胞凋亡,pCMV-HGF保护组tBid及细胞色素C的表达明显减少。结论通过小鼠尾静脉高压注射的方法在肝细胞中建立持续表达外源性HGF的体系,通过抑制Bid的活性片段tBid表达和细胞色素C释放来减轻凋亡蛋白的激活。     

血清肝细胞生长因子在慢性肝病中的意义

目的 肝细胞生长因子(HGF)能促进上皮细胞增生、运动、变形，是肝再生的起始因子之一，近来发现其在肝硬化和肝肿瘤的发生发展中也有重要作用。现主要探讨血清HGF水平在慢性肝病中的意义。方法 检测197例个体血清HGF水平，包括肝细胞癌(HCC)80例，肝硬化(LC)57例，慢性肝炎(CH)22例，正常对照38例。ELISA法检测血清HGF水平，并描绘受试者工作曲线(ROC)，确定HCC和LC患者HGF水平的最佳临界点。运用Spearman相关分析HGF水平和ALT、AST、GGT、白蛋白、总胆红索、凝血时间、肝癌大小、病理分级的相关性。结果 HCC、LC、CH和正常对照组的血清HGF中位值分别是6．767、151．200、7．017和3．476pg／m1。其中HCC组(P＜0．05)和比组(P＜0．01)的血清HGF水平显著高于正常对照组。LC组根据Child分级分层发现，Child C级患者的HGF水平明显高于Child A、B级。肝硬化ROC曲线显示，14pg／m1为临界值时效率最高。血清HGF水平仅发现与凝血时间有相关性(r=0．45，P＜0．01)。在HCC组中，未发现血清HGF水平与肿瘤大小、病理分级有任何相关。结论 血清中HGF水平增高与LC程度有关。     

离散因子/肝细胞生长因子cDNA转染对肝癌SMMC7721细胞生长和转移的影响

目的 通过离散因子／肝细胞生长因子（scatter factor/Hepatocyte factor,SF/HGF）cDNA转染肝癌SMMC7721细胞来探讨SF／HGF对肝癌生长和转移的影响。方法 用脂质体法进行基因转染,以ELISA和western blot检测SF／HGF及其受体c-met的表达,通过生长曲线、划良实验比较转染前后细胞的增长状况及细胞的运动能力。以转染前后细胞分别接种裸鼠,观察移植的生长及转移情况。结果 转染后细胞表达SF／HGF的量为694pg/ml,其受体c-met量未见明显变化;转染后细胞增殖明显加快,运动能力增强,并伴明显的形态学变化。初步动物实验显示转染后细胞生长较快,瘤组织中有瘤栓形成,并在肺内发现转移灶。结论 SF／HGF在肝癌细胞中的高表达能促进肝癌细胞生长、侵袭及转移。     

Effect of matrine on transforming growth factor β1 and hepatocyte growth factor in rat liver fibrosis model

Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly divided into A,B,C,D groups with 12 in each,group A as the normal control group and groups B.C,D as liver fibrosis models using composite modulus method with carbon tetrachloride(CCL_4).Group B was the model group,group C adopted γ— interferon lavage therapy in the second day of modeling,and group D adopted matrine lavage treatment,at 4 and8 weeks after treatment.Six rats were executed for detection of TGF- β1 and HGF,liver tissue histology and comparison fibrosis degree changes of rat liver tissue between groups.Results:Croups B,C,D showed a more significantly increased TCF- β1 at each time point compared with group A(P0.05);Group B showed a more significantly increased TGF- β1 than groups C and D at weeks 4 and 8(P0.05);group D showed a lowest level of TGF-β1,followed by groups C and B.HGF of group B decreased more significantly than A group at weeks 4 and 8(P0.05);HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B(P0.05),in which the group D showed the highest level of HGF.According to tissue histologic observation,rat liver tissue structure of group A was clear and normal,tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells;groups C and D showed a slighter liver tissue damage,cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious improvement.Conclusions:Matrine can reduce TGF- β1expression and enhance the activity of HGF,so as to realize the inhibition effect on liver fibrosis in rats.     

Role of circulating vascular endothelial growth factor and hepatocyte growth factor in patients with coronary artery disease

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are thought to stimulate endothelial cell proliferation and induce angiogenesis in vivo. However, the precise mechanism responsible for VEGF and HGF release in patients with coronary artery disease is still unknown. We studied serum concentrations of VEGF and HGF in 20 patients with acute myocardial infarction (AMI), 20 patients with stable angina pectoris (AP) who had reversible perfusion defects on stress myocardial scintigraphy, and 16 patients with old myocardial infarction (OMI) who had no reversible defects on stress myocardial scintigraphy. The control group consisted of 20 patients with atypical chest pain who had angiographically normal coronary arteries. Serum VEGF and HGF concentrations were measured by enzyme-linked immunosorbent assay. Both the serum VEGF and HGF concentrations in the early stage of myocardial infarction in the patients with AMI were higher than those in the patients with AP and with OMI, and control patients. The VEGF concentration in the patients with AP was higher than in the patients with OMI, whereas the HGF concentration did not differ in the patients with AP and OMI. The VEGF concentration in AMI patients who had had preinfarction angina on admission was higher than that of patients who had had no preinfarction angina, whereas the HGF concentration did not differ between the two groups of patients. These results suggest that the serum VEGF concentration may reflect myocardial ischemia to a greater degree than the serum HGF concentration. Received June 9, 2000 / Accepted September 30, 2000     

人肝细胞生长因子基因重组腺病毒载体的构建

目的:利用ADEASYTM系统,构建高效而又安全的肝细胞生长因子(HGF)基因腺病毒载体(AdHGF),以研究HGF基因在心脏内的表达。方法:从人胎肝中抽提总RNA,并以该肝细胞总RNA为模版,利用合成的1对引物,采用RTPCR技术获得HGF基因的cDNA,并引入酶切位点,先转入感受态质粒,再转化大肠杆菌进行扩增,筛选阳性菌落,经酶切及测序,证实目的HGF基因已经转入,再将该基因转入pUC18质粒,pUC18质粒与AdEASY质粒进行同源重组,用PacⅠ酶切成线性化DNA,利用脂质胺转染293细胞,经3轮扩増,制备高效表达并用绿色荧光标志AdHGF。并将该载体作实验组,与HGF组作比较,观察对VEC的抗凋亡作用。结果:在荧光显微镜发现293细胞发光率为100%,AdHGF的HGFcDNA经过测序鉴定与基因库序列一致。结论:AdHGF的成功构建,为冠心病转基因治疗的基础与临床研究奠定了基础。     

肝细胞生长因子与肝纤维化的研究进展

肝细胞生长因子是一种具有多种生物活性的细胞因子,其在促进肝细胞增殖、抑制肝星状细胞活化等方面有重要作用.肝纤维化进展过程中,各种因素引起肝细胞持续损伤,使损伤部位肝细胞再生,肝星状细胞激活,细胞外基质大量沉积,从而导致肝纤维化形成.此文就肝细胞生长因子的生物学特性及其在肝纤维化中发挥的作用作一综述.