血小板衍生生长因子及其受体在肝纤维化患者肝组织中的表达及意义

目的：研究血小板衍生生长因子（PDGF）及受体（PDGFR）在慢性肝炎纤维化和肝硬化患者肝组织中的表达，分布和意义。方法：用免疫组织化学方法检测了21例慢性肝炎，42例肝硬化患者肝组织中PDGF－A，PDGF－B，PDGFR－α，PDGFR-β及α－平滑肌肌动蛋白（α－SMA）的表达，分布状况，定量和相关性分析。结果：慢性肝炎和肝硬化组织PDGF及其受体和α－SMA的表达主要分布于汇管，纤维间隔和炎细胞浸润聚集区，尤其见带分支突出的梭形细胞（活化的HSC）有大量表达。PDGF－B和PDGFR－β表达分别强于PDGF－A和PDGFR－α，两组间差异有显著性（P＜0．05－0．01）。α－SMA与PDGF－A，PDGF－B及PDGFR－α，PDGFR－β的表达，分布基本一致，定量分析呈正相关，相关系数分别为0．606（P＜0．001），0．772（P＜0．001），0．684（P＜0．001），0．825（P＜0．001）。结论：PDGF及其受体在肝纤维化发生发展中起重要作用，是通过活化HSC发挥效应，研究抑制PDGF及其受体的产生和作用是防治肝纤维化的新途径。     

Inhibitory effect of human interferon-beta-1a on activated rat and human hepatic stellate cells

Background and Aims: Hepatic stellate cells (HSC) are the primary cell type mediating hepatic fibrosis. Although known for its antiviral effects, the inhibitory effects of interferon‐beta (IFN‐β) on HSC treatment have not yet been established. Methods: Both human and rat activated HSC cell lines were incubated with increasing concentrations of recombinant human IFN‐β1a (rhIFN‐β1a) for 24, 48 or 72 h. The effects of rhIFN‐β1a on α‐smooth muscle actin (α‐SMA), collagen types I and III, transforming growth factor‐β1 (TGF‐β1), platelet‐derived growth factor‐BB (PDGF‐BB), and mothers against decapentaplegic homolog (Smad4, Smad7) expression in HSC were examined using Western blotting and immunocytochemistry. Proliferation of HSC was evaluated via bromodeoxyuridine assay. Results: rhIFN‐β1a treatment had a dose‐dependent, inhibitory effect on α‐SMA and collagen type I protein expression. In addition, rhIFN‐β1a decreased the expression of collagen type III, TGF‐β1, PDGF‐BB and Smad4 protein expression in HSC compared with untreated cells. We also observed increased Smad7 protein expression and decreased proliferation in rhIFN‐β1a‐treated HSC. Conclusions: Our data suggest that rhIFN‐β1a treatment decreased α‐SMA and collagen expression and inhibited the activation of HSC through the inhibition of the TGF‐β and PDGF pathways.     

Intracellular pH regulation and Na+/H+ exchange activity in human hepatic stellate cells: effect of platelet-derived growth factor, insulin-like growth factor 1 and insulin

BACKGROUND/AIMS: The Na+/H+ exchanger is involved in rat hepatic stellate cell (HSC) proliferation induced by platelet-derived growth factor (PDGF). We therefore evaluated in human HSC: (1) the mechanisms of intracellular pH regulation; (2) the relationship between Na+/H+ exchange activation and cell proliferation induced by PDGF, insulin-like growth factor 1 (IGF-1) and insulin. METHODS/RESULTS: pH(i) regulation was mainly dependent on the activity of the Na+/H+ exchanger, which was evaluated by measuring pH(i) recovery from an acute acid load. PDGF (25 ng/ml) gradually increased the activity of the Na+/H+ exchanger which peaked at 18 h and remained stable until the 24th h. IGF-1 (10 nmol/l), but not insulin (100 nmol/l), slightly but significantly increased the activity of the Na+/H+ exchanger. Amiloride (100 micromol/l) and 20 micromol/l 5-N-ethyl-N-isopropyl-amiloride completely inhibited HSC proliferation (evaluated by measurement of bromodeoxyuridine incorporation) induced by PDGF and IGF-1, but did not affect proliferation of HSC induced by insulin. Finally, IGF-1 did not modify the activity of the Na+/Ca2+ exchanger. CONCLUSIONS: The Na+/H+ exchanger is involved in HSC proliferation induced by PDGF and IGF-1, whereas the proliferative effect of insulin is mediated by intracellular pathways which are Na+/H+ exchange-independent.     

Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption.

Hypervitaminosis A-related liver toxicity may be severe and may even lead to cirrhosis. In the normal liver, vitamin A is stored in hepatic stellate cells (HSC), which are prone to becoming activated and acquiring a myofibroblast-like phenotype, producing large amounts of extracellular matrix. AIMS: In order to assess the relationship between vitamin A intake, HSC activation and fibrosis, we studied nine liver biopsies from patients belonging to a well-characterized series of 41 patients with vitamin A hepatotoxicity. METHODS: Fibrosis was underlined by Sirius-red staining, whereas activated HSC were immunohistochemically identified using an antibody against alpha smooth muscle actin. The volume density (Vv) of sinusoidal and total fibrosis and of sinusoidal and total activated HSC was quantified by the point-counting method. RESULTS: Morphology ranged from HSC hypertrophy and hyperplasia as the sole features to severe architectural distortion. There was a significant positive correlation between Vv of perisinusoidal fibrosis and the daily consumption of vitamin A (P=0.004). CONCLUSION: The close correlation between the severity of perisinusoidal fibrosis and the daily dose of the retinol intake suggests the existence of a dose-effect relationship.     

白细胞介素10对肝星状细胞激活的调节

目的 探讨白细胞介素10(IL-10)通过血小板衍生生长因子(PDGF)和丝裂原活化激酶(MAPK)信号通路蛋白对肝星状细胞(HSC)激活的影响。 方法 将培养的HSC随机分为4组:1组:对照组;2组:加入1 ng/ml IL-10;3组:加入5 ng/ml IL-10;4组:加入25 ng/ml IL-10。培养2d后,逆转录-聚合酶链反应法检测各组细胞中PDGF mRNA的表达;western blot法检测各组细胞PDGF、MAPK信号通路蛋白细胞外信号调节激酶(ERK)和p38以及α-平滑肌肌动蛋白(α-SMA)的表达。 结果 1、5、25 ng/ml的IL-10作用后,与对照组相比HSC的ERK、p38以及α-SMA的表达显著降低(F值分别为240.47、21.39、28.86,P值均<0.01),并呈量效依赖关系;5、25 ng/ml的IL-10可以使PDGF表达显著降低(P值均<0.01),并呈量效依赖关系。 结论 IL-10可通过PDGF/MAPK信号通路抑制肝星状细胞激活。     

去甲肾上腺素对大鼠肝星状细胞作用的实验研究

目的 探讨交感神经系统在肝纤维化发生和发展中的作用. 方法采用免疫荧光和RT-PCR检测体外培养的肝星状细胞(HSC)中α1、β2-肾上腺素能受体的表达;用四甲基偶氮唑盐法检测不同浓度的去甲肾上腺素(NE)对HSC增殖活性的影响.同时用RT-PCR检测受NE作用后HSC的活化指标胶原蛋白-1、转化生长因子β(TGF β)及α-平滑肌动蛋白(α-SMA)的表达.用高效液相色谱-电化学法测定活化的HSC中交感神经递质NE的水平. 结果α1和β2-肾上腺素能受体表达于HSC的胞膜和胞质内;NE可呈剂量依赖性地促进HSC增殖,在浓度为100μmol/L时达到最大效应,F=140.464,P<0.05,差异有统计学意义.以NE 100 μmol/L作用细胞24h后,可显著促进反应HSC活化的指标上升,胶原蛋白-1表达为0.3022±0.0610,TGF β表达为2.2080±0.2151,α-SMA mRNA表达为0.5469±0.0108,与对照组胶原蛋白-1(0.1040±0.0556)、TGF β(1.1190±0.0070)、α-SMA mRNA表达(0.0759±0.0449)比较,t值分别为-4.160、-8.763和-17.651,P值均<0.05,差异均有统计学意义.HSC可以合成并释放NE,且受血小板衍生生长因子(10ng/ml)刺激后HSC中NE含量为(14.24±0.21)ng/ml,对照组为(11.34±0.15)ng/ml,两组比较,t=-32.907,P<0.05,差异有统计意义.结论 抑制交感神经系统使HSC活性降低对临床上治疗肝纤维化有一定的指导意义.     

Fibrogenic cell phenotype modifications during remodelling of normal and pathological human liver in cultured slices

Background: The debate concerning the potential remodelling and/or reversibility of cirrhotic lesions and biliary fibrosis is still open. Aims/Methods: In this work, we have used the precision‐cut liver slice (PCLS) model, which maintains cell–cell and cell–matrix interactions to study, by immunohistochemistry, the behaviour of the different fibrogenic cells, i.e. hepatic stellate cells (HSC) and portal fibroblasts, in cultured (for 1 week) PCLS derived from normal and fibrotic human livers. Results: In normal liver, before and after culture, α‐smooth muscle (SM) actin was present only in the vessel walls. Platelet‐derived growth factor (PDGF) receptor‐β was expressed before and after culture by portal fibroblasts, and appeared after culture in HSC. Before culture, CD 34 was not expressed in parenchyma, but appeared after culture in sinusoidal endothelial cells. In cirrhotic lesions, before culture, α‐SM actin, PDGF receptor‐β and Thy‐1 were expressed in septa; after culture, α‐SM actin expression disappeared but the expression of the PDGF receptor‐β and Thy‐1 was maintained. In cholestatic liver specimens, α‐SM actin, PDGF receptor‐β and Thy‐1 expression, which was present before culture in enlarged portal areas, disappeared after culture, and apoptosis was detected. In the parenchyma of both cirrhotic and cholestatic livers, the expression of the PDGF receptor‐β and of CD 34, which was not observed before culture, was present in HSC and sinusoidal endothelial cells, respectively, after culture. Conclusions: These results indicate that during remodelling of pathological tissues in cultured liver slices, the myofibroblastic cells derived from HSC or from portal fibroblasts show different behaviours, suggesting different mechanisms of activation/deactivation.     

Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo

BACKGROUND: Following liver injury, hepatic stellate cells (HSC) transform into myofibroblast-like cells (activation) and are the major source of type I collagen and the potent collagenase inhibitors tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) in the fibrotic liver. The reproductive hormone relaxin has been reported to reduce collagen and TIMP-1 expression by dermal and lung fibroblasts and thus has potential antifibrotic activity in liver fibrosis. AIMS: To determine the effects of relaxin on activated HSC. METHODS: Following isolation, HSC were activated by culture on plastic and exposed to relaxin (1-100 ng/ml). Collagen deposition was determined by Sirius red dye binding and radiolabelled proline incorporation. Matrix metalloproteinase (MMP) and TIMP expression were assessed by zymography and northern analysis. Transforming growth factor beta1 (TGF-beta1) mRNA and protein levels were quantified by northern analysis and ELISA, respectively. RESULTS: Exposure of activated HSC to relaxin resulted in a concentration dependent decrease in both collagen synthesis and deposition. There was a parallel decrease in TIMP-1 and TIMP-2 secretion into the HSC conditioned media but no change in gelatinase expression was observed. Northern analysis demonstrated that primary HSC, continuously exposed to relaxin, had decreased TIMP-1 mRNA expression but unaltered type I collagen, collagenase (MMP-13), alpha smooth muscle actin, and TGF-beta1 mRNA expression. CONCLUSION: These data demonstrate that relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation.     

罗格列酮对免疫性肝纤维化大鼠肝组织IGF-1表达的影响

目的探讨免疫性肝纤维化大鼠肝组织中胰岛素样生长因子-1(IGF-1)的表达变化,并观察罗格列酮对其的影响。方法应用猪血清腹腔注射诱导大鼠肝纤维化模型,适时给予罗格列酮干预。采用ELISA法检测血清IGF-1水平和免疫组织化学法检测肝组织IGF-1的表达。结果与对照组相比,第4、6、8周模型组大鼠血清及肝组织IGF-1水平均显著升高(P<0.05);与模型组相比,8周罗格列酮组大鼠纤维化程度减轻(P<0.01),血清及肝组织IGF-1表达水平降低(P<0.01)。结论随肝纤维化进展,大鼠血清和肝组织IGF-1的表达均增强,罗格列酮可降低肝组织IGF-1的表达,因而能减轻大鼠肝纤维化。     

Relationship between hepatic progenitor cell‐mediated liver regeneration and non‐parenchymal cells

Hepatic progenitor cells (HPCs) are thought to reside in the canals of Hering and can be activated and contribute to liver regeneration in response to liver injury by proliferating and differentiating towards both hepatocytes and biliary epithelial cells. In this setting, several cytokines, chemokines, and growth factors related to liver inflammation and other liver cells comprising the HPC niche, namely hepatic stellate cells (HSCs), play crucial roles in HPC activation and differentiation. In response to several types of liver injury, tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) is secreted by several inflammatory cells, including monocytes, T lymphocytes, and macrophages, and acts as an initiator of the HPC niche and HSC activation. Following TWEAK‐induced activation of the HPC niche, fibroblast growth factor 7 and hepatocyte growth factor released from activated HSC play central roles in maintaining HPC proliferation. In contrast, HGF‐MET and Wnt3a‐β‐catenin signals are the predominant mediators of the hepatocyte differentiation of HPC, whereas epidermal growth factor receptor–NOTCH signaling controls HPC differentiation towards biliary epithelial cells. These signals are maintained exclusively by activated HSC and inflammatory cells surrounding HPC. Together, HSC and inflammatory cells surrounding HPC are responsible for the precise control of HPC proliferation and differentiation fate. In this review, we discuss recent progress in understanding of interactions between HPC and other liver cells in HPC‐mediated liver regeneration in the setting of liver inflammation.     

Inverse association between hepatic stellate cell apoptosis and fibrosis in chronic hepatitis C virus infection

Summary.  Perisinusoidal hepatic stellate cells (HSC) are the principal fibrogenic cells in the liver. In animal models, HSC apoptosis is the predominant clearance mechanism of activated HSC, although data evaluating whether the same processes occur in humans are limited. We conducted a cross-sectional study to evaluate the association between HSC apoptosis and fibrosis stage in subjects with chronic hepatitis C virus (HCV) infection ( n  = 44) and HCV-negative controls with normal liver histology ( n  = 9). We used immunohistochemical techniques to identify activated (α-smooth muscle actin⁺), proliferative (Ki-67⁺) and apoptotic (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end-labelling⁺) HSC in liver biopsy specimens from all subjects. The same pathologist enumerated positive cells per high-power field (HPF, ×200) in 20 periportal/lobular areas. HSC apoptosis was decreased in HCV-positive subjects compared with controls (median 0.4, range 0.0–3.1 vs 1.1, 0.2–3.5 cells/HPF, P  =   0.02). Among HCV-positive subjects, HSC apoptosis was decreased in those with moderate to advanced fibrosis ( P  = 0.04) compared with those with mild fibrosis. By multivariate analysis, HSC apoptosis decreased by an average of 0.14 cells/HPF (95% confidence interval 0.01–0.28 cells/HPF) per increase in fibrosis stage ( P  = 0.04). While the number of activated and proliferative HSC was significantly increased in HCV-infected subjects compared with that in uninfected controls, the numbers of these cells did not differ between HCV-infected subjects with mild vs moderate/advanced fibrosis. In conclusion, the number of apoptotic HSC was significantly decreased in HCV-infected subjects with advanced fibrosis. In chronic HCV infection, inhibition of HSC apoptosis may be one mechanism by which fibrosis progresses.     

抗纤软肝颗粒对血小板源生长因子诱导的肝星状细胞增殖的影响

目的:研究抗纤软肝颗粒(KXR)对血小板源生长因子(PDGF)诱导的肝星状细胞(HSC)增殖的影响.方法:采用无血清培养,不同浓度的KXR温育HSC 24 h后,PDGF-BB(10 ng/ml)刺激24 h,再加入上述浓度的KXR 3 h后,又加入PDGF-BB(10 ng/ml)作用5 min,然后收集细胞.采用细胞计数法及流式细胞仪测定细胞增殖及细胞周期.结果:无血清培养显示该方对于PDGF诱导的细胞增殖具有抑制作用,并呈剂量依赖性(P<0.01).流式细胞术分析提示KXR能抑制PDGF诱导的HSC DNA合成期及合成后期和分裂期DNA百分含量,阻断细胞由静止期/DNA合成前期向DNA合成期转化,呈剂量依赖性(5 mg/ml组作用最显著,P<0.01).结论:KXR能抑制PDGF诱导的HSC增殖.     

Active matrix metalloproteinase‐2 promotes apoptosis of hepatic stellate cells via the cleavage of cellular N‐cadherin

Background and Aims: Hepatic stellate cells (HSC) are known to synthesise excess matrix that characterises liver fibrosis and cirrhosis. Activated HSC express the matrix‐degrading matrix metalloproteinase enzymes (MMPs) and their tissue inhibitors (TIMPs). During spontaneous recovery from experimental liver fibrosis, the expression of TIMP‐1 declines and hepatic collagenolytic activity increases. This is accompanied by HSC apoptosis. In this study, we examine a potential mechanism whereby MMP activity might induce HSC apoptosis by cleaving N‐cadherin at the cell surface. Results: N‐cadherin expression was upregulated in human HSC during activation in culture. Addition of function‐blocking antibodies or a peptide targeting the extracellular domain of N‐cadherin, to cultured HSC, promoted apoptosis. During apoptosis, there was cleavage of N‐cadherin into 20–100 kDa fragments. MMP‐2 became activated early during HSC apoptosis and directly cleaved N‐cadherin in vitro. Addition of activated MMP‐2 to HSCs in culture resulted in enhanced apoptosis and loss of N‐cadherin. Conclusions: Together, these studies identify a role for both N‐cadherin and MMP‐2 in mediating HSC apoptosis, where N‐cadherin works to provide a cell survival stimulus and MMP‐2 promotes HSC apoptosis concomitant with N‐cadherin degradation.     

Reversibility of secondary biliary fibrosis by biliodigestive anastomosis in the rat.

Biliary cirrhosis with portal hypertension and hepatocellular failure is a well-known complication of extrahepatic obstruction. It is unclear to what extent these changes are reversible by biliodigestive anastomosis. Therefore a rat model of relief of biliary obstruction was developed by performing Roux-en-Y choledochojejunostomy in rats after bile duct obstruction. Patency of the biliodigestive anastomosis was documented by biliary scintigraphy. Microsomal function was assessed in vivo by the aminopyrine breath test and portal hypertension by spleen pulp pressure. Microsomal function was markedly impaired in obstructed animals but recovered after biliodigestive anastomosis. Microsomal cytochrome P450 content paralleled these changes. Similarly, portal hypertension was reversed after successful relief of obstruction. Stereologic analysis showed that biliodigestive anastomosis partially reversed bile ductular proliferation and fibrosis. Studying the time course of recovery showed that restoration of microsomal function was achieved after 2 weeks whereas recovery from portal hypertension required 4 weeks of biliary drainage. Recovery of microsomal function was paralleled by normalization of microsomal lipid composition while resolution of portal hypertension occurred parallel to resolution of the histologic abnormalities.     

Proanthocyanidin derived from the leaves of Vaccinium virgatum suppresses platelet‐derived growth factor‐induced proliferation of the human hepatic stellate cell line LI90

Aim: Hepatic stellate cell (HSC) proliferation plays a pivotal role in liver fibrogenesis, and agents that suppress HSC activation, including platelet‐derived growth factor (PDGF)‐induced HSC proliferation, are good candidates for antifibrogenic therapies. In this report, we use the LI90 HSC line to elucidate the antifibrogenic effects of proanthocyanidin derived from the leaves of Vaccinium virgatum. Methods: Proanthocyanidin (PAC) was extracted from the leaves of blueberry V. virgatum (BB‐PAC), grape seeds (GS‐PAC) and Croton lechleri (CL‐PAC). These extracts were examined for their effects on PDGF‐BB‐induced LI90 cell proliferation and DNA synthesis. Extracellular signal‐regulated kinase (ERK) and Akt phosphorylation and PDGF receptor‐β (PDGFR‐β) expression were evaluated by western blot analysis. Results: BB‐PAC potently suppressed PDGF‐BB‐induced proliferation and DNA synthesis of LI90 cells. BB‐PAC also suppressed PDGF‐BB‐induced DNA synthesis in primary cultured rat HSC. Moreover, GS‐PAC and CL‐PAC suppressed PDGF‐BB‐induced DNA synthesis in LI90 cells. In contrast, the monomeric PAC catechin and epicatechin and dimeric PAC procyanidin B2 only slightly suppressed PDGF‐BB‐induced DNA synthesis. Western blot analysis showed that BB‐PAC completely or partially inhibited PDGF‐BB‐induced ERK and Akt phosphorylation, respectively. In addition, BB‐PAC partially inhibited the PDGF‐BB‐induced degradation of PDGFR‐β. Conclusion: Our results suggest that BB‐PAC suppresses activated HSC by inhibiting the PDGF signaling pathway. In addition, these results provide novel findings that may facilitate the development of antifibrogenic agents.     

大鼠结缔组织生长因子部分cDNA序列的克隆及其mRNA在实验性 …

目的 克隆出大鼠结缔组织生长因子（ｃｏｎｎｅｃｔｉｖｅ ｔｉｓｓｕｅ ｇｒｏｗｔｈ ＣＴＧＦ）的部分ｃＤＮＡ序列,并观察在实验性肝经大鼠肝脏中ＣＴＧＦ ｍＲＮＡ的表达改变。方法 根据小鼠ＣＴＧＦ ｍＲＮＡ序列设计引物,用ＲＴ－ＰＣＲ从大鼠肝脏总ＲＮＡ中扩增出一段４３０ｂｐ的产物,并测定其序列,将１６只雌性Ｗｉｓｔａｒ大鼠随机为胆管堵塞组（ｎ＝８）及假手术组（ｎ＝８）,６周后取大鼠提取总ＲＮＡ,利用     

Fenretinide stimulates the apoptosis of hepatic stellate cells and ameliorates hepatic fibrosis in mice

Aim: To investigate whether fenretinide, a clinically proved apoptosis‐inducing chemopreventive agent in tumor cells, can induce apoptosis in hepatic stellate cells (HSCs) and resolve hepatic fibrosis. Methods: CCl₄‐induced liver fibrosis in mice and rat activated hepatic stellate cells (HSC‐T6) as well as hepatocytes (BRL‐3A) were studied. Results: The duplex staining of proliferating cell nuclear antigen and α‐ smooth muscle actin or terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labeling and α‐ smooth muscle actin demonstrated that fenretinide executed its anti‐fibrosis effect in liver by inducing apoptosis rather than inhibiting proliferation of HSCs, while it had no apparently apoptotic effect on hepatocytes. Fenretinide could elicit apoptosis of HSC‐T6 in vitro at the concentration range from 0.5 to 5 µM, but at higher concentrations ≥5 µM was required to induce apoptosis in hepatocytes (BRL‐3A). Conclusion: Further studies using malondialdehyde measurement, Western blot, antioxidant, inhibitors for p53, caspase 8 and 9 – as well as anti‐Fas neutralizing antibody – have shown that in HSC‐T6, fenretinide‐induced apoptosis involves a reactive oxygen species (ROS)‐generated, P53‐independent, mitochondria‐associated intrinsic pathway, whereas in hepatocytes (BRL‐3A), a ROS‐generated, P53‐dependent, Fas‐related extrinsic pathway is triggered only at high concentration.     

生长因子对HSC-T6细胞c-fos和c-jun基因表达的影响

目的 了解血小板衍生生长因子(PDGF)和转化生长因子β(TGF β)分别对肝星状细胞c～fos和c-jun基因表达的影响.方法 在培养的肝星状细胞系HSC-T16细胞中分别加入不同浓度的PDGF(终浓度分别为8、40、200 ng/ml)和TGF β(终浓度分别为0.2,1.0、5.0 ng/ml);于8、24,48、72h四个时间点分别收集细胞,提取细胞总RNA;用逆转录定量PCR法测定c～los和c-jun的基因表达水平.结果 PDGF处理的3组HSC-T6细胞8、24、48、72h时,c-fos基因表达水平均明显高于对照组,并呈剂量依赖性l培养8 h时达到表达最高峰,对照组,PDGF 8 ng/ml组,PDGF 40 ng/ml组,PDGF 200ng/ml组c-fos表达分别为0.63±0.13,1.13±0.19、1.75±0.20、2.40±0.23,3组间差异有统计学意义(F=7.03,P<0.01).TGF β处理的3组HSC-T6细胞8、24,48、72 h时,c-iun基因表达水平均明显高于对照组,并呈剂量依赖性,培养8 h时达到表达最高峰,对照组,TGF β 0.2ng/ml组、TGF β 1.0ng/ml组、TGF β 5.0ng/ml组cjun基因表达分别为0.93±0.13、1.69±0.26、2.34±0.30、2.96士0.37; 3组间差异有统计学意义(F=6.34,P<0.01).结论 PDGF和TGF β分别对肝星状细胞c-los和c-jun基因表达有明显的上调作用.