Quercetin activates an angiogenic pathway, hypoxia inducible factor (HIF)-1-vascular endothelial growth factor, by inhibiting HIF-prolyl hydroxylase: a structural analysis of quercetin for inhibiting HIF-prolyl hydroxylase

We investigated a molecular mechanism underlying quercetin-mediated amelioration of colonic mucosal injury and analyzed chemical structure contributing to the quercetin's effect. Quercetin up-regulated vascular endothelial growth factor (VEGF), an ulcer healing factor, not only in colon epithelial cell lines but also in the inflamed colonic tissue. VEGF derived from quercetin-treated colon epithelial cells promoted tube formation. The VEGF induction was dependent on quercetin-mediated hypoxia-inducible factor-1 (HIF-1) activation. Quercetin delayed HIF-1alpha protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1alpha hydroxylation and subsequent von Hippel Lindau-dependent HIF-1alpha degradation. HPH inhibition by quercetin was neutralized significantly by an elevated dose of iron. Consistent with this, cellular induction of HIF-1alpha by quercetin was abolished by pretreatment with iron. Two iron-chelating moieties in quercetin, -OH at position 3 of the C ring and/or -OH at positions 3' and 4' of the B ring, enabled the flavonoid to inhibit HPH and subsequently induce HIF-1alpha. Our data suggest that the clinical effect of quercetin may be partly attributed to the activation of an angiogenic pathway HIF-1-VEGF via inhibiting HPH and the chelating moieties of quercetin were required for inhibiting HPH.     

Tetramethylpyrazine inhibits hypoxia-induced pulmonary vascular leakage in rats via the ROS-HIF-VEGF pathway

Tetramethylpyrazine (TMP) is a reactive oxygen species (ROS) antagonist that has potent properties for the treatment of a variety of vascular diseases, such as ischemic stroke and pulmonary hypertension secondary to chronic obstructive pulmonary diseases. However, there are few data about the role of TMP in hypoxia-induced pulmonary vascular leakage. This study examined the effect of TMP on hypoxia-induced pulmonary vascular leakage and the underlying mechanisms. Rat pulmonary microvascular endothelial cells (RPMVECs) treated with TMP or not were subjected to hypoxic or normoxic conditions for 24 h, and the monolayer permeability, intracellular ROS, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins levels were determined. Additionally, rats administrated TMP were exposed to hypobaric hypoxia to evaluate the effect of TMP in vivo by measuring lung water content, pulmonary vascular leakage into the lungs and immunohistochemistry for HIF-1α and VEGF. Hypoxia was found to cause a significant increase in RPMVEC monolayer permeability and intracellular ROS, HIF-1α and VEGF protein levels. Treatment with TMP decreased the hypoxia-induced RPMVEC monolayer permeability and attenuated the elevation of ROS, HIF-1α and VEGF protein levels. TMP-treated animals showed less pulmonary vascular leakage and HIF-1α and VEGF expression compared with those exposed to hypoxia alone. These observations supported that TMP inhibited the increase in pulmonary vascular permeability induced by hypoxia. The underlying mechanisms may be related to the scavenging of intracellular ROS and the suppression of hypoxia-induced upregulation of HIF-1α and VEGF proteins.     

Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) in A549 cells. HIF-1α plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1α was correlated with a rapid ubiquitin-dependent degradation of HIF-1α, and was accompanied by increased expressions of hydroxyl-HIF-1α and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1α inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGFβ1/PHD2/HIF-1α pathway, as demonstrated by the transfection of TGFβ1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1α transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.     

链霉素及H7对机械牵张离体心肌HIF-1α、VEGF的影响及机制探讨

目的研究链霉素及H7对机械牵张大鼠心肌组织低氧诱导分子-1α和血管内皮细胞生长因子表达的影响,并探讨二者在其中的作用机制。方法采用大鼠离体灌流心脏模型,膨胀左心室30min,RT-PCR法检测左室心肌细胞HIF-1α、VEGF mRNA的表达,免疫组化观察二者在心肌细胞中定位,Western blot检测HIF-1α蛋白的表达,利用链霉素作为牵张敏感离子通道(SACs)阻断剂研究SACs和PKC抑制剂H7在其中的可能作用。结果与不牵张组HIF-1α和VEGF mRNA无表达的比较,牵张可以明显增加HIF-1α和VEGF mRNA的表达(P<0·05或P<0·01);而链霉素、H7可以明显减少HIF-1α和VEGF mRNA的表达(P<0·05);但是二者不能完全抑制急性牵张刺激激活的HIF-1α和VEGF mRNA水平升高(P<0·05),HIF-1α和VEGF在胞质和胞核中均有表达,并检测到HIF-1α蛋白表达。结论链霉素、H7对膨胀左室致HIF-1α、VEGF表达有明显抑制作用,提示心室膨胀经SACs-PKC-激活胞内信号诱导HIF-1α、VEGF表达。同时链霉素并不能完全抑制HIF-1α、VEGF表达,提示膨胀心室致HIF-1α、VEGF表达进而引起心室肥厚尚有其他传导途径,仍需进一步研究。     

口腔鳞癌组织中ALG-2、HIF-1α和VEGF的表达水平及临床意义

目的 观察分析口腔鳞癌(oral squamous cell carcinoma,OSCC)组织中凋亡相关基因-2(ALG-2)、缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)的表达情况,探讨ALG-2、HIF-1α和VEGF对OSCC患者的临床意义.方法 选取2015年5月-2016年5月48例OSCC患者口腔黏膜癌变组织(研究组)和同期48例正常者口腔黏膜组织(对照组)作为研究对象,比较两组口腔黏膜组织ALG-2、HIF-1α和VEGF的表达情况,并分析其与OSCC临床病理特征的相关性.结果 研究组中ALG-2、HIF-1α和VEGF总阳性率均明显高于对照组(P＜0.05).在OSCC组织分化程度上,高分化组ALG-2、HIF-1α和VEGF总阳性率均明显低于低分化组(P＜0.05).不同分期OSCC癌组织中ALG-2、HIF-1α和VEGF总阳性率比较差异无统计学意义(P＞0.05).结论 OSCC口腔黏膜癌变组织中ALG-2、HIF-1α和VEGF的表达可考虑作为临床评估OSCC病情的指标.     

HIF-1α和VEGF在大鼠COPD中的表达及与肺血管重构的关系研究

目的探讨HIF-1α、VEGF在COPD各阶段的表达情况及其与肺血管重构的关系。方法 24只♂SD大鼠随机分为3个组,每组8只。正常对照组(A):d 1、14气道内注入生理盐水,4周后检测;慢支组(B):d 1、14经气道内注入脂多糖(LPS),200μg/次,4周后检测;COPD组(C):d 1、14气道内注入LPS,200μg/次,香烟烟雾暴露1 h.d-1,共4周。各组测定气道阻力及平均肺动脉压力(mPAP)。HE染色观察肺组织病理改变,VG+维多利亚蓝特殊染色检测肺血管重构指标:肺小动脉血管壁厚度与血管外径比(WT%)、血管壁面积与血管总面积比(WA%)。RT-PCR、Western blot分别检测各组肺组织匀浆中HIF-1α、VEGF mR-NA及蛋白表达情况。分析HIF-1α、VEGF的表达情况与肺血管重构指标的相关性。结果①与A组相比,C组气道阻力、mPAP增加(P<0.05)。②VG+维多利亚蓝特殊染色显示C组WT%、WA%值高于A组。③RT-PCR、Westernblot结果显示,C组HIF-1αmRNA及蛋白表达较A组明显增加,B、C组VEGF mRNA表达逐渐增强,C组VEGF蛋白表达较A组明显增加。HIF-1α、VEGF表达情况均与肺血管重构指标WT%、WA%呈正相关,(P<0.05)。结论 HIF-1α、VEGF与COPD的发病密切相关,其通过促进肺血管重构加重COPD的病情。改善缺氧状态及拮抗HIF-1α、VEGF的表达,尤其是在早期对VEGF的干预,可以减轻COPD的肺血管重构,减缓其到肺动脉高压的进展。     

肿瘤坏死因子受体-抗体融合蛋白对佐剂性关节炎大鼠滑膜中TNF-α、HIF-1α和VEGF表达的影响

目的探讨肿瘤坏死因子受体-抗体融合蛋白（益赛普）对佐剂性关节炎大鼠滑膜中肿瘤坏死因子-α（TNF-α）、缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）表达的影响。方法将成年雄性Wistar大鼠随机分为5组,Ⅱ～Ⅴ组建立佐剂性关节炎大鼠（AA）模型,于造模后第12天开始Ⅲ组给予甲氨喋呤灌胃治疗,Ⅳ～Ⅴ组给予益赛普皮下注射治疗。第28天取膝关节滑膜,常规HE染色,计算滑膜病理积分,免疫组织化学染色检测TNF-α、HIF-1α和VEGF在膝关节滑膜的表达。结果Ⅰ组大鼠滑膜组织均有少量TNF-α、HIF-1α和VEGF的表达,Ⅱ～Ⅴ组较Ⅰ组均明显增高。Ⅳ、Ⅴ组滑膜组织TNF-α表达较Ⅱ组明显减低（P〈0.01）而Ⅲ组与Ⅱ组差异无统计学意义。Ⅲ～Ⅴ组滑膜组织HIF-1α、VEGF的表达均明显低于Ⅱ组,差异有统计学意义（P〈0.01）。结论益赛普可明显降低AA大鼠滑膜组织TNF-α、HIF-1α和VEGF表达。益赛普可以降低AA大鼠的关节炎指数、足体积,减轻足肿胀程度,对AA大鼠的关节炎症有明显的治疗作用。     

缺氧诱导因子1α和血管内皮细胞生长因子在非霍奇金淋巴瘤中表达的研究

目的 研究缺氧诱导因子1α(H1F-1α)、血管内皮细胞生长因子(VEGF)、微血管密度(MVD)在淋巴瘤患者淋巴结中的表达及其与淋巴瘤的关系.方法 采用免疫组化方法测定28例淋巴瘤患者及(试验组)27例淋巴结炎患者对照组淋巴结组织中的HIF-1α、VEGF、MVD表达.结果 试验组和对照组MVD、VEGF、HIF-1α水平差异有统计学意义[分别为是(57.2±10.7)%比(38.3±11.2)%、(38.5±6.6)%比(21.3±6.3)%、(39.2±4.5)%比(24.5±4.8)%,均P＜0.05].结论 非霍奇金淋巴瘤患者淋巴结中HIF-1α、VEGF、MVD水平均较淋巴结炎患者增高,HIF-1α可能通过调节VEGF的水平从而促进新生血管的形成.

Abstract：

Objective To examine the expression of plasma hypoxia-inducible factor 1 alpha (HIF-1 α),vascular endothelial growth factor (VEGF) and microvessel density (MVD) of patients with NHL. Methods Totally 28 cases in NHL group( group A) and 27 cases in control one( group B) were enrolled. We examined the expression of HIF-1α, VEGF and MVD in tissue samples with immunohistochemical stain of two groups respectively.Results The levels of HIF-1α, VEGF and MVD in the two groups respectively with significant statistical difference. Conclusions The levels of HIF-1 α, VEGF and MVD in patients with NHL is higher than that of in lymphadenitis. It's possible that HIF-1α can promote MVD via adjusting VEGF level.     

HIF-α、VEGF 和 DLL4在非小细胞肺癌中的表达及临床意义

目的：探讨 Delta 样配体4（ Delta-like ligand 4,DLL4）、低氧诱导因子α（ hypoxia inducible factor alpha, HIF-α）和血管内皮生长因子（ vascular endothelial growth factor,VEGF）在非小细胞肺癌（ non-small cell lung cancer, NSCLC）中的表达及其临床意义。方法选取河北省胸科医院胸外科2012年10月—2015年11月经手术治疗 NSCLC患者的手术切除标本72例作为 NSCLC 组,另选距离原发肿瘤5 cm 以上的肺组织标本（经 HE 染色病理证实无肿瘤浸润）72例作为正常对照组。通过免疫组化染色的方法检测 DLL4、HIF-α及 VEGF 的表达情况,并结合患者的临床病理资料进行分析。结果 NSCLC 组 DLL4、HIF-α及 VEGF 阳性表达率显著高于正常对照组（ P ﹤0.01）;DLL4、HIF-α及VEGF 表达与 NSCLC 肿瘤分化程度、临床分期、淋巴结转移有关（ P ﹤0.05）,而与患者年龄、性别、病理类型及肿瘤长径无关（P ﹥0.05）;DLL4、HIF-α与 VEGF 表达两两之间均呈显著正相关（ r =0.320、0.366、0.335,P ﹤0.01）。结论DLL4、HIF-α及 VEGF 在 NSCLC 发生、发展和转移中可能起协同作用,检测 DLL4、HIF-α及 VEGF 的表达对临床判断非小细胞肺癌发生、发展、预后及研发新的靶向治疗药物有一定的价值。     

VEGF、HIF-1α在不同前列腺病变组织中的表达及临床意义

目的 探讨血管内皮生长因子(VEGF)、缺氧诱导因子-1α(HIF-1α)在不同前列腺病变组织中的表达及临床意义.方法 应用免疫组化法分别检测30例前列腺增生组织、30例前列腺上皮内瘤变组织及70例前列腺癌组织VEGF、HIF-1α表达情况.结果 VEGF与HIF-1α在前列腺癌组织中的阳性表达率明显高于前列腺增生和前列腺上皮内瘤变组织,差异有统计学意义(P<0.01);VEGF及HIF-1α的表达均与前列腺癌的Gleason分级、TNM临床分期、骨及淋巴结转移相关(P<0.05);VEGF、HIF-1α在前列腺癌组织中表达呈正相关(r=0.63,P<0.01).结论 VEGF、HIF-1α在前列腺癌发生演变过程中起着重要作用,可通过检测两者的表达情况判断预后.     

心肌转染缺氧诱导因子-1α对大鼠心肌梗死的影响

目的评价心肌内注射缺氧诱导因子(HIF)-1α进行基因转染对大鼠心肌梗死的影响,包括HIF-1α、血管内皮生长因子(VEGF)的基因表达、血中VEGF水平、心肌毛细血管密度以及心肌梗死面积的变化。方法选择体质量在250~350 g的雄性大鼠72只进行实验,分为3组,第1组为转染腺病毒HIF-1α的Ad-HIF-1α组;第2组为转染空质粒的Ad-null组(转染空质粒组);第3组为假手术组。每组以术后的不同时间处死取材分3,7,14 d 3个亚组,每个亚组8只。建立心肌梗死模型。当左前降支被结扎后,在室游离壁的3个不同部位分别注射50μg Ad-HIF-1α和50μg的Ad-dull,然后关胸缝合。假手术组不结扎左前降支。分别在转染3、7及14d后观察HIF-1α和VEGF的基因表达、血中VEGF水平、心肌毛细血管密度以及心肌梗死面积的变化。结果转染腺病毒HIF-1α基因的心肌组织中第3天即可测出478 bp的HIF-1α及291 bp VEGF部分转录产物,第7、14天检测仍有表达,而Ad-dull组的心肌组织有表达,但相对于转染腺病毒HIF-1α基因的心肌组织表达明显较弱;血中VEGF水平在Ad-HIF-1α组比Ad-null组在37、d升高更显著(P<0.01);心肌转染组的毛细血管密度与未转染组相比明显增加(P<0.01);转染14 d后的心肌梗死面积在转染组为(23.8±2.2)%,明显小于对照组的(38.7±3.1)%(P<0.01)。结论心肌内注射HIF-1α进行基因转染可以增加HIF-1α和VEGF的基因表达,血中VEGF水平升高,心肌毛细血管密度明显增加,心肌梗死面积明显减少。     

缺氧诱导因子-1α在胶质瘤中的表达及意义

目的探讨缺氧诱导因子-1α（HIF-1α）在人脑不同级别胶质瘤中的表达,分析HIF-1α、血管内皮生长因子（VEGF）和微血管密度（MVD）之间的相互关系及意义。方法采用免疫组化法检测54例胶质瘤组织中HIF-1α及VEGF的表达情况,并以VIII-R-Ag作为标记计数微血管密度（MVD）。结果58例胶质瘤组织HIF-1α的表达阳性率为65.5%（33/58）,HIF-1α的表达强度和胶质瘤的病理分级呈正相关（χ2=14.24,P〈0.05）。HIF-1α的表达和VEGF的表达呈正相关（χ2=4.02,P〈0.05）,HIF-1α和MVD呈正相关（t=3.22,P〈0.05）。结论HIF-1α与人脑胶质瘤组织中血管生成及病理分级密切相关,为治疗胶质瘤的提供一种可能的途径。     

Molecular biomarkers of cantharidin-induced cardiotoxicity in Sprague-Dawley rats: Troponin T,vascular endothelial growth factor and hypoxia inducible factor-1α

Early diagnosis of cantharidin-induced myocardial injury is the key to reduce the fatality rate in clinical practice. The purpose of the present study was to explore biomarkers that can be used for the prediction and diagnosis of cantharidin-induced myocardial injury. Of 65 male Sprague-Dawley rats weighing 200-230 g, 25 rats were divided into five groups according to the administration dose of cantharidin (0, 1.34, 2.67, 4 and 5.34 mg/kg; n = 5 per group) and the other 40 rats were treated with 2.67 mg/kg cantharidin and divided into nine groups according to the administration time (0, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours; n = 4 per group). Pathological changes of hypoxia, necrosis and inflammation were confirmed in heart samples that were exposed to cantharidin by hematoxylin-eosin staining and overall scores of pathological changes among heart samples in cantharidin exposure groups showed an increasing trend compared with in the control group. Coexpression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and caspase9 was shown in the myocardium by immunofluorescence staining. Western blotting results showed that expression of VEGF, HIF-1α and caspase9 in cantharidin-treated rat hearts showed an increasing trend compared with in the control group. Results of enzyme-linked immunosorbent assay suggested that plasma levels of troponin T (TN-T), VEGF and HIF-1α were elevated at different intervals after cantharidin administration, and VEGF and HIF-1α had a significant linear relationship with TN-T that was verified by multiple linear regression analysis. Preliminary results serve to illustrate that TN-T, VEGF and HIF-1α might be valuable molecular markers in cantharidin-induced myocardial injury and that diagnostic accuracy needs to be studied further.     

Echinomycin decreases induction of vascular endothelial growth factor and hepatocyte regeneration in acetaminophen toxicity in mice

Up-regulation of vascular endothelial growth factor (VEGF) is important to hepatocyte regeneration in the late stages of acetaminophen (APAP) toxicity in the mouse. This study was conducted to examine the relationship of hypoxia-inducible factor 1α (HIF-1α) to VEGF and hepatocyte regeneration in APAP toxicity using an inhibitor of HIF-1α DNA-binding activity, echinomycin (EC). B6C3F1 male mice were treated with APAP (200 mg/kg IP), followed by EC (0.15 mg IP) and killed at 4 hr. Serum alanine aminotransferase (ALT), necrosis, hepatic glutathione (GSH) and APAP protein adducts were comparable in the APAP/EC and the APAP/veh mice at 4 hr. Additional studies showed that high dose EC (0.3 mg) reduced hepatic VEGF but also lowered hepatic GSH. Subsequent studies were performed using the 0.15-mg dose of EC. Although EC 0.15 mg had no effect on hepatic VEGF levels at 8 hr, by 24 hr VEGF levels were decreased by 40%. Toxicity (ALT and histopathology) was comparable in the APAP and APAP/EC groups at 24 and 48 hr. Proliferating cell nuclear antigen expression was reduced by both Western blot analysis and immunohistochemical staining in the APAP/EC mice at 48 hr. The data support the hypothesis that induction of HIF-1α, its binding to DNA and subsequent expression of VEGF are important factors in hepatocyte regeneration in APAP toxicity in the mouse.     

HIF-1α、VEGF在乳腺癌中的表达及其与化疗敏感性的关系

目的 探讨HIF-1α、VEGF在乳腺癌中的表达及其与新辅助化疗敏感性的关系.方法 应用免疫组织化学S-P法检测52例乳腺癌患者新辅助化疗前、后瘤体组织HIF-1α、VEGF的表达,评估其与化疗疗效的关系.结果 化疗前乳腺癌HIF-1α阳性表达为46.15％,化疗后降到21.15％,差异有统计学意义（P＜0.05）;VEGF的表达化疗前为55.77％,化疗后降到30.77％,差异有统计学意义（P＜0.05）.化疗前后HIF-1α的表达与VEGF正相关,P＜0.05.新辅助化疗前HIF-1α和VEGF表达阳性者均较阴性者化疗敏感性差,P＜0.05.结论 HIF-1α和VEGF可作为乳腺癌化疗敏感性的预测因子,有助于制定个体化化疗方案.     

Signaling pathways for arsenic-stimulated vascular endothelial growth factor-a expression in primary vascular smooth muscle cells

Chronic arsenic exposure is associated with an increased risk for cancer, cardiovascular disease (including ischemic heart disease and hypertension), peripheral vascular disease, and diabetes. Arsenic causes blood vessel growth and remodeling in vivo and cell specific, dose-dependent induction vascular endothelial growth factor-A (VEGF), which is essential for both processes. The current study examined the hypothesis that low, environmentally relevant levels of trivalent arsenic (AsIII) activate discrete signaling pathways in vascular smooth muscle cells (SMC) to induce expression of VEGF. AsIII caused a progressive increase in VEGF mRNA levels over a 48 h period in primary porcine SMC with a threshold of 1-2.5 microM. VEGF protein levels increased with a similar concentration dependence and time course. Hypoxia inducible factor-1alpha (HIF-1alpha) protein and mRNA levels also increased in response to AsIII. However, unlike the response to an iron chelator, AsIII-induced VEGF was not inhibited by siRNA directed toward HIF-1alpha. Instead, a novel protein kinase C, PKCdelta, was activated by AsIII to induce VEGF and stabilize HIF-1alpha. Consistent with this activation, AsIII caused coordinate increases in the levels of the intracellular second messenger diacyglycerol (DAG). These data suggest that AsIII induced divergent signaling pathways in SMCs that lead to independent increases in VEGF expression and HIF-1alpha signaling. However, these pathways both require initial increases in DAG levels and PKC activity.     

HIF-1α和VEGF在宫颈鳞癌组织中的表达及其意义

目的:探讨缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在宫颈鳞癌组织中的表达及其意义.方法:采用免疫组化SP法检测HIF-1α仅和VEGF在11例正常宫颈组织,32例宫颈鳞状上皮非典型增生和48例宫颈鳞癌组织的表达特点及相关性.结果:HIF-1α在正常宫颈组织、宫颈上皮内瘤变(CIN)及宫颈癌组织中的表达率依次升高,分别为0%,15.6%(5/32)和47.9%(23/48),3组比较差异有显著性(P<0.05).VEGF在正常宫颈组织、CIN及宫颈癌组织中的表达率依次升高,分别为0%,21.9%(7/32)和54.2%(26/48),3组比较差异有显著性(P<0.05).低分化鳞癌组织中HIF-1α、VEGF的表达率高于高-中分化鳞癌组织(P<0.05).有淋巴结转移鳞癌组织中HIF-1α、VEGF的表达率高于无淋巴结转移鳞癌组织(P<0.05).鳞癌组织中HIF-1α、VEGF的表达之间存在明显关系(P<0.05).结论:HIF-1α、VEGF在宫颈鳞癌的发生发展中起重要作用,HIF-1α可通过调节VEGF的表达促进肿瘤血管形成及其恶性进展.