实验性肺纤维化形成过程中肺组织血管生成的动态变化

目的观察大鼠肺纤维化形成过程中肺组织血管生成的动态变化及其与肺纤维化形成的关系.方法免疫组织化学方法结合透射电镜观察博莱霉素组和对照组肺组织血管生成的变化,同时测定羟脯氨酸含量评估肺纤维化程度.结果博莱霉素组大鼠早期有血管计数一过性的明显升高,到第八天达到高峰,血管新生的区域与肺纤维化区域相吻合;随着胶原纤维的沉积,血管逐渐减少最后近于消失.电镜显示肺损伤后早期毛细血管内皮细胞表现出细胞核增大,常染色质增多,细胞器丰富等增生旺盛表现.结论肺纤维化早期血管生成显著,血管生成在肺纤维化发生发展中可能起重要作用.     

COPD大鼠肺组织中小窝蛋白-1 的表达及其与气道重塑的关系

目的:探讨小窝蛋白-1(Caveolin-1)在COPD大鼠肺组织中的表达及其与气道重塑的关系。方法:采用10周龄Wister大鼠20只,随机分为对照组与实验组,每组10只,对照组常规饲养,实验组采用烟熏法+内毒素法建立COPD模型。第91天处死全部大鼠,测定肺功能后取肺组织,采用免疫组织化学法检测Caveolin-1的表达;酶联免疫吸附试验(ELISA)检测各组大鼠肺组织匀浆中白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)的含量;分析Caveolin-1的表达与IL-8、TNF-α、TGF-β表达的相关性。结果:与对照组比较,实验组大鼠的肺顺应性明显下降,肺弹性阻力及气道阻力显著升高,肺组织TNF-α、IL-8、TGF-β1的含量明显升高,Caveolin-1的表达明显降低,差异均有统计学意义(P0.05)。大鼠肺组织中Caveolin-1的表达与IL-8、TNF-α、TGF-β1含量呈显著负相关(P0.05)。结论:Caveolin-1在COPD大鼠肺组织中的表达明显降低,可能通过促进炎性细胞因子的释放与气道重塑参与COPD的发生和发展。     

大鼠肺纤维化形成中肺内肥大细胞结缔组织生长因子的表达

目的：观察博莱霉素（BLM）诱导肺纤维化形成中肺肥大细胞（MCs）是否表达结缔组织生长因子（CTGF）。方法：32只雄性SD大鼠,随机分为博莱霉素（BLM）组和对照（Control）组（n=16）。BLM组为气管内一次性滴注BLM（5mg／ks）;Control组为气管内滴注与BLM等容量的生理盐水（NS）。各组分别在气管滴注后第14天和第28天处死大鼠,取肺组织样本。用氯胺-T法检测肺组织羟脯氨酸含量以判断肺纤维化程度;用甲苯胺蓝染色显示肺组织切片中的MCs;免疫组化染色显示肺CTGF的表达和分布。结果：①与对照大鼠比,气管内滴注BLM后第28天大鼠的肺羟脯氨酸含量明显增高（P〈0．01）。②与对照大鼠比,气管内滴注BLM后第14天和第28天大鼠肺内MCs数明显增多（均P〈0．01）,肺内CTGF表达上调（均P〈0．01）。③对照大鼠肺内未见CTGF免疫阳性的MCs;而气管内滴注BLM后第14天和第28天大鼠肺内病灶区中有CTGF免疫阳性的MCs。结论：肺纤维化形成中肺MCs表达CTGF,这可能是MCs促进肺纤维化的作用机制之一。     

急性肺损伤大鼠肺组织高迁移率族蛋白1的表达及其意义

目的动态观察高迁移率族蛋白1（HGMB1）在失血性休克复合内毒素注射致急性肺损伤（ALl）大鼠肺组织的表达情况,初步探讨HMGB1在ALI发病机制中的作用。方法采取失血性休克复合内毒素注射手段建立ALl大鼠动物模型,采用RT-PCR方法,检测肺组织HMGB1mRNA的表达情况。结果正常大鼠肺组织有少量HMGBlmRNA表达,遭受失血性休克复合内毒素注射打击后,HMGB1mRNA表达迅速升高,至ALI24h达最高峰,随后有所下降,ALl各组大鼠表达水平与正常对照组比较差异均有统计学意义（P〈0．01）。结论正常大鼠肺组织有一定水平HMGBlmRNA的表达,遭受失血性休克及内毒素注射打击后,HMGBlmRNA表达异常增高,可引起过度炎症反应,从而促进ALI的发生与发展。     

急性冷暴露对大鼠肺组织中水通道蛋白AQP-1和AQP-5表达的影响

目的：探讨急性冷暴露后肺组织超微结构变化以及对水通道蛋白-1（AQP-1）和AQP-5表达的影响。方法：12只健康雄性Wistar大鼠随机分为室温（23℃±2℃）对照组和-25℃ 2 h冷暴露组（n=6）;记录冷暴露后大鼠直肠温度;透射电镜观察肺组织超微结构改变;RT-PCR法和Western blot法测定大鼠肺组织AQP-1和AQP-5基因和蛋白的表达水平。结果：急性冷暴露后大鼠的体心温度与对照组相比,明显降低（P<0.05）;肺组织超微结构亦发生改变,基底膜明显增厚,肺泡I上皮细胞（AT-I）核固缩,肺泡Ⅱ上皮细胞（AT-Ⅱ）胞浆空泡化增多;冷暴露后大鼠肺组织AQP-1的基因和蛋白表达未见明显变化,AQP-5的基因和蛋白表达均显著降低（P<0.05）。结论：急性冷暴露肺组织AQP-5基因和蛋白表达降低与寒冷暴露引发肺组织结构损伤可能存在一定因果关系。     

罗格列酮和强的松对博来霉素诱导大鼠肺纤维化中FIZZ1表达的影响

目的:观察Fizz1在肺组织中的动态表达及其意义,并比较罗格列酮与强的松对Fizz1表达的影响。方法:90只雄性SD大鼠随机分为对照组,模型组,强的松干预组,罗格列酮干预组,强的松+罗格列酮干预组,模型组和干预组大鼠气管内一次性注入博来霉素构建大鼠肺纤维化模型,对照组给予等量生理盐水。造模24小时后各干预组给予相应药物灌胃。各组动物于7、14、28d随机处死6只,测肺系数,取肺组织病理切片行HE和Masson染色,观察肺泡炎和纤维化程度,测肺组织羟脯氨酸含量,免疫组化法检测Fizz1在肺组织中的表达情况。结果:干预组各时期肺纤维化程度均较模型组轻。Fizz1表达呈动态性变化,第7天表达最高,14 d,28 d表达减弱。干预组各时期Fizz1表达水平较模型组降低,其中罗格列酮和强的松联合干预组早期对Fizz的下调水平更大。结论:Fizz1的表达上调可能参与博来霉素诱导的肺纤维化形成;罗格列酮、强的松均可下调Fizz1表达减轻博来霉素诱导的肺纤维化程度,减少肺组织胶原的沉积,提示Fizz1可成为肺纤维化治疗的新靶点,罗格列酮和强的松联用治疗较单用强的松效果更好,对Fizz1的下调水平更大。     

罗格列酮和强的松对博来霉素诱导大鼠肺纤维化中FIZZ1表达的影响

目的：观察Fizzl在肺组织中的动态表达及其意义,并比较罗格列酮与强的松对Fizzl表达的影响。方法：90只雄性SD大鼠随机分为对照组,模型组,强的松干预组,罗格列酮干预组,强的松＋罗格列酮干预组,模型组和干预组大鼠气管内一次性注入博来霉素构建大鼠肺纤维化模型,对照组给予等量生理盐水。造模24小时后各干预组给予相应药物灌胃。各组动物于7、14、28d随机处死6只,测肺系数,取肺组织病理切片行HE和Masson染色,观察肺泡炎和纤维化程度,测肺组织羟脯氨酸含量,免疫组化法检测Fizzl在肺组织中的表达情况。结果：干预组各时期肺纤维化程度均较模型组轻。Fizzl表达呈动态性变化,第7天表达最高,14d,28d表达减弱。干预组各时期Fizzl表达水平较模型组降低,其中罗格列酮和强的松联合干预组早期对Fizz的下调水平更大。结论：Fizzl的表达上调可能参与博来霉素诱导的肺纤维化形成;罗格列酮、强的松均可下调Fizzl表达减轻博来霉素诱导的肺纤维化程度,减少肺组织胶原的沉积,提示Fizzl可成为肺纤维化治疗的新靶点,罗格列酮和强的松联用治疗较单用强的松效果更好,对Fizzl的下调水平更大。     

硝基还原酶结构域蛋白1在大鼠睾丸组织中特异性高表达在人类睾丸癌中表达下调

通过克隆分离鉴定得到大鼠硝基还原酶结构域蛋白1(rNOR1),发现rNOR1 cDNA含有1 418 个碱基,编码含379个氨基酸残基的rNOR1蛋白．rNOR1与人类NOR1 (hNOR1)和小鼠NOR1 (mNOR1)的同源性分别为89% 和93%,这三种同源蛋白都含有OSCP1家族的保守结构域．rNOR1基因在大鼠睾丸中选择性高表达,而且与之同源的人类hNOR1也选择性高表达于睾丸中．通过免疫组化检测人类不同睾丸癌中的hNOR1蛋白表达,发现hNOR1蛋白在非癌变睾丸组织和胚胎性癌组织中高表达,而在精原细胞癌和分化型非精原细胞癌(畸胎瘤,卵黄囊瘤)中低表达．这些数据表明,hNOR1可能是一种睾丸选择性表达基因,睾丸癌hNOR1表达的改变或许可以帮助我们阐明hNOR1蛋白在生殖细胞系肿瘤发生中的功能．     

实验性变态反应性脑脊髓炎大鼠发病中脑组织血红素氧合酶-1基因和蛋白表达的动态变化

为探讨脑组织血红素氧合酶-1(hemeoxygenase-1,HO-1)对实验性变态反应性脑脊髓炎(experimental allergic encephalomyelitis,EAE)的作用,分别应用逆转录-聚合酶链反应(RT-PCR)和免疫组化技术测定了豚鼠脊髓生理盐水匀浆 完全福氏佐剂诱导EAE大鼠1、7、14、21d时,脑组织HO-1基因和蛋白表达的动态变化,并观察与症状之间的关系。结果显示：对照组大鼠脑组织仅有少量HO-1基因和蛋白表达：诱导EAE后,伴随着大鼠EAE症状及脑组织病理损伤的出现和进行性加重,脑组织HO-1基因和蛋白表达量逐渐增高。在豚鼠脊髓生理盐水匀浆 完全福氏佐剂诱导7d后,HO-1 mRNA上升至高峰。14d时,HO-1蛋白表达至高峰,HO-1阳性细胞主要位于脉络丛、穹隆下器、血管“套袖样”病灶的周围,与EAE病变部位一致。此时大鼠的病情最重、体重减轻最显著、脑组织病理改变最明显。21d时脑组织HO-1基因和蛋白表达量逐渐下降,大鼠EAE症状也逐渐减轻。应用HO-1特异性抑制剂锡原卟啉-9以抑制脑内HO-1蛋白表达后,大鼠EAE症状和脑组织损伤明显减轻,说明脑组织HO-1的动态变化与EAE症状及脑组织损伤密切相关。提示脑组织HO-1基因和蛋白过表达对EAE发病起着重要的作用,应用HO-1抑制剂可能是防治该病的有效方法之一。     

Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis

Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries in a rat ectopic cardiac allograft model. We previously reported that AIF-1 is associated with the pathogenesis of rheumatoid arthritis and skin fibrosis in sclerodermatous graft-versus-host disease mice. Here, we used an animal model of bleomycin-induced lung fibrosis to analyze the expression of AIF-1 and examine its function in lung fibrosis. The results showed that AIF-1 was expressed on lung tissues, specifically macrophages, from mice with bleomycin-induced lung fibrosis. Recombinant AIF-1 increased the production of TGF-β which plays crucial roles in the mechanism of fibrosis by mouse macrophage cell line RAW264.7. Recombinant AIF-1 also increased both the proliferation and migration of lung fibroblasts compared with control group. These results suggest that AIF-1 plays an important role in the mechanism underlying lung fibrosis, and may provide an attractive new therapeutic target.     

Metastasis-associated protein 1 promotes epithelial-mesenchymal transition in idiopathic pulmonary fibrosis by up-regulating Snail expression

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually fatal lung disease that lacking effective interventions. It is well known that aberrant activation of transforming growth factor-beta1 (TGF-β1) frequently promotes epithelial-mesenchymal transition (EMT) in IPF. Metastasis-associated gene 1 (MTA1) has identified as an oncogene in several human tumours, and aberrant MTA1 expression has been related to the EMT regulation. However, its expression and function in IPF remain largely unexplored. Using a combination of in vitro and in vivo studies, we found that MTA1 was significantly up-regulated in bleomycin-induced fibrosis rats and TGF-β1-treated alveolar type Ⅱ epithelial (RLE-6TN) cells. Overexpression of MTA1 induced EMT of RLE-6TN cells, as well as facilitates cell proliferation and migration. In contrast, knockdown of MTA1 reversed TGF-β1-induced EMT of RLE-6TN cells. The pro-fibrotic action of MTA1 was mediated by increasing Snail expression through up-regulating Snail promoter activity. Moreover, inhibition of MTA1 effectively attenuated bleomycin-induced fibrosis in rats. Additionally, we preliminarily found astragaloside IV (ASV), which was previously validated having inhibitory effects on TGF-β1-induced EMT, could inhibit MTA1 expression in TGF-β1-treated RLE-6TN cells. These findings highlight the role of MTA1 in TGF-β1-mediated EMT that offer novel strategies for the prevention and treatment of IPF.     

Yin Yang-1(YY-1) expression in idiopathic pulmonary fibrosis

Context: Yin Yang-1 (YY-1) is implicated in the pathogenesis of lung cancer which can be complicated with idiopathic pulmonary fibrosis (IPF).

Objective: The aim of the study was to investigate whether YY-1 is involved in the pathogenesis of IPF and whether represents a common pathogenetic pathway which could explain the coexistence of these disorders.

Materials and methods: Lung tissue from 52 patients (37 with IPF and 15 controls) and bronchoalveolar lavage fluid (BALF) from 34 patients (25 with IPF and 9 controls) were studied and YY-1 mRNA expression was evaluated by real-time PCR.

Results: YY-1 was expressed in 8% (3/37) of IPF patients and in 6% (1/15) of healthy controls in tissue samples. In addition, 12% (3/25) of IPF patients and 33% (3/9) of healthy controls have expressed YY-1 gene in BALF samples. However, no statistical significant difference in mRNA expression between patients and controls has been detected in both tissue and BAL fluid samples.

Discussion and conclusion: Our results do not support the hypothesis of YY-1 involvement in IPF. However, similar expression of YY-1 gene in two biological samples cannot exclude a possible role of this polymorphic gene in the pathway of IPF. Further studies in a larger scale of patients are needed.     

基于数据库中肺纤维化miRNA及肺癌mRNA芯片资料分析筛查肺癌的潜在治疗靶点

肺癌严重危害人类健康,患者预后较差。肺纤维化是肺癌的危险因素之一,与肺癌的发病机制存在一定关系。肺纤维化中失调的微小RNA(microRNA, miRNA)在肺癌发生发展过程中发挥着重要作用。本研究使用基因表达综合数据库(Gene Expression Omnibus, GEO)中肺纤维化miRNA及肺癌mRNA的芯片数据,利用GEO2R筛选肺纤维化差异miRNA与肺癌差异基因、miRWalk预测miRNA靶基因、STRING分析互作关系、WebGestalt进行GO与KEGG分析、GEPIA分析基因对患者生存的影响,最终获得SNRPE、PIK3R1、ARHGEF6等潜在的肺癌治疗靶点。通过对这些潜在靶点的认识进一步了解肺癌的发生发展机制,为肺癌的临床治疗贡献新的思路。     

Overproduction of collagen and diminished SOCS1 expression are causally linked in fibroblasts from idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal pulmonary disorder, and its pathology is characterized by parenchymal fibrosis. To investigate the characteristics of fibroblasts in IPF, we obtained eight fibroblast cell lines from lungs with IPF and eight lines from normal lungs. We found that the fibroblasts from IPF spontaneously produced higher amounts of type I collagen and had lower expression levels of SOCS1 than fibroblasts from normal lung. By using mouse fibroblasts, we demonstrated the causal relationship between them: the deficiency of SOCS1 in fibroblasts resulted in increased collagen production, whereas overexpression of SOCS1 suppressed collagen production. IFN-gamma suppressed spontaneous collagen production even in SOCS1-deficient fibroblasts, indicating that IFN-gamma inhibition is SOCS1-independent. In contrast, IFN-gamma suppressed the increase of collagen production induced by IL-4 in wild type fibroblasts but not SOCS1-deficient fibroblasts, suggesting IFN-gamma acted exclusively via SOCS1 in this case. Following IFN-gamma stimulation, the amount of SOCS1 mRNA expressed by IPF fibroblasts was comparable to that of normal fibroblasts. Thus, the extent of SOCS1 increase after stimulation by IFN-gamma was significantly higher in IPF fibroblasts. The extent to which IFN-gamma inhibited collagen production was also larger in IPF fibroblasts than in normal fibroblasts. These results suggest that the exaggerated production of collagen observed in fibroblasts from IPF is causally related to the diminished expression of SOCS1, and IPF fibroblasts are more susceptible to IFN-gamma because of decreased expression of SOCS1.     

基质金属蛋白酶及其抑制剂在肝纤维化中的表达变化

目的 观察肝纤维化形成过程中基质金属蛋白酶MMP-1及其抑制剂TIMP-1的表达变化,从细胞外基质降解代谢的角度研究四氯化碳(CCl4)中毒性肝纤维化发生的机制.方法 雄性Wistar大鼠20只,分为正常组和肝纤维化模型组.肝纤维化组采用CCl4、饮酒、高脂低蛋白饮食等复合病因刺激制备肝纤维化动物模型,造模时间为8周.实验结束后测定肝脏指数、血清透明质酸(HA)、谷丙转氨酶(ALT)及尿羟脯氨酸(HYP)排出量,光镜下观察肝组织纤维化程度,并用免疫组化SABC法检测肝组织中Ⅰ、Ⅲ型胶原蛋白及MMP-1、TIMP-1的表达,同时用荧光实时定量PCR(RT-PCR)的方法检测肝组织中MMP-1、TIMP-1 mRNA的表达.结果 与正常对照组比较,肝纤维化模型组大鼠肝脏指数、血清HA及ALT显著增高,尿羟脯氨酸的排出量明显增加,病理组织学检查发现肝组织内纤维结缔组织增生明显,有假小叶形成;免疫组化的结果显示肝组织内Ⅰ、Ⅲ型胶原蛋白、MMP-1及TIMP-1的表达较正常组显著增加.结论 肝组织中MMP-1及TIMP-1的表达变化可能是导致肝纤维化的重要机制之一.     

不同剂量博莱霉素诱导小鼠肺纤维化的差异及动态变化

目的探讨博来霉素诱导小鼠肺纤维化最佳剂量和方法。方法 126只8周龄雄性ICR小鼠,随机分成一次性大剂量模型和多次小剂量模型。一次性大剂量模型分为200 mg/(kg.bw)BLM组、150 mg/(kg.bw)BLM组、100 mg/(kg.bw)BLM组及阴性对照组(DN组),每组18只,分别经尾静脉一次性注射BLM 200、150、100mg/(kg.bw)及生理盐水10 mL/(kg.bw),各组分别于第7、14、21天各处死6只。多次小剂量模型分为每日10 mg/(kg.bw)BLM组及阴性对照组(N组),分别经尾静脉注射BLM 10 mg/(kg.bw)及生理盐水10 mL/(kg.bw),每天1次,连续注射14 d,两组分别于第14、21、28天各处死6只。留取肺组织,观察肺组织病理改变,检测Ⅲ型胶原的含量,观察小鼠体重及生存率。结果①在一次性大剂量模型中,BLM各剂量组肺泡炎症评分及肺纤维化评分与正常组相比,除100 mg/(kg.bw)BLM组和150 mg/(kg.bw)BLM组在第7天的模型差异无显著性外(P>0.05),其余各组差异均有显著性(P<0.05);各个剂量组Ⅲ型胶原的表达面积与正常组相比,除100 mg/(kg.bw)BLM组在第7天的模型差异无显著性外(P>0.05),其余各组均较正常组高(P<0.05),各个剂量组分别在第21天达到高峰,以200 mg/(kg.bw)BLM组第21天组Ⅲ型胶原的表达面积最高;该模型小鼠各剂量组死亡率为0。②在多次小剂量模型中,各组的肺泡炎症与肺纤维化程度与正常组相比差异均有显著性(P<0.05);各组Ⅲ型胶原的表达也均高于正常组(P<0.05),且随着时间的延长呈进行性增加,在第28天达到高峰;该模型小鼠共死亡11只,死亡率为30.56%。结论在本实验中,以尾静脉一次性注射BLM 200 mg/(kg.bw)后第21天诱导建立的ICR小鼠肺纤维化模型成模最好,其小鼠死亡率低,操作简单,有效安全方便的特点使之有希望成为一种复制肺纤维化的理想模型。     

Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

Background

Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls.

Methods

Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MC_T and MC_TC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β.

Results

In the alveolar parenchyma in lungs from patients with CF, MC_TC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MC_TC and MC_T cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MC_TC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MC_TC correlated positively with the degree of fibrosis. The increased density of MC_TC, as well as MC_TC expression of TGF-β, correlated negatively with patient lung function.

Conclusions

The present study reveals that altered mast cell populations, with increased numbers of MC_TC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.     

吸入糖皮质激素对大鼠肺纤维化的干预作用及bFGF表达的影响

目的:研究吸入糖皮质激素对大鼠肺纤维化模型的干预作用及可能的机制。方法:雌性Wistar大鼠40只,体重180～250g,按照随机数字表法将大鼠随机分为4组(n=10):①对照组(C组);②模型组(M组);③布地奈德组(B组);④地塞米松组(D组)。M组、B组、D组给大鼠气管内吸入博莱霉素(5mg/kgbw,8mg)复制肺纤维化模型,C组气管内吸入同等剂量的生理盐水作对照,B组于次日给予雾化吸入等效剂量布地奈德,D组于次日腹腔内注射地塞米松。上述各组均于注药后第1、4周各宰杀5只。通过苏木素-伊红染色观察肺泡炎、Masson胶原染色观察肺纤维化、用免疫组化及酶联免疫吸附测定(ELISA)法检测bFGF蛋白在大鼠肺组织,血清及肺泡灌洗液(BALF)的表达。结果:1、4周时M组表现为肺泡炎及肺间质炎症,B组、D组肺泡炎及肺纤维化程度较M组减轻。1、4周时血清、肺组织、BALF中M组的bFGF表达高于C组(P0.01),B、D组低于M组(P0.01)。结论:吸入糖皮质激素可减轻博莱霉素诱导的肺纤维化,其抗纤维化作用的机制与抑制bFGF表达有关。