血管内皮生长因子和微血管密度在鼻息肉形成中的作用

目的:探讨血管内皮生长因子(VEGF)的蛋白表达,微血管密度(MVD)与鼻息肉的关系.方法:应用免疫组织化学SP法检测50例鼻息肉组织中和10例下鼻甲组织中VEGF的蛋白表达情况,并用图像分析仪测定其平均灰度值,对两者之间的关系及和MVD之间的关系进行统计学分析.结果:①VEGF在鼻息肉组织中的表达量明显高于下鼻甲组织(P＜0.05).②鼻息肉组织中MVD与下鼻甲组织中MVD之间差异有统计学意义(P＜0.05).③鼻息肉组织中VEGF在血管中的平均灰度值均与MVD负相关(r=-0.664,P＜0.05).结论:在鼻息肉组织中,VEGF蛋白表达增多, MVD增加提示:VEGF在鼻息肉的发生发展中起了关键性作用.联合检测VEGF蛋白表达情况及MVD对鼻息肉的治疗、预防复发及制定有效合理的治疗方案具有重要的参考价值.     

白细胞介素17与血管内皮生长因子在鼻息肉组织中的表达及相关性分析

目的　通过研究鼻息肉组织中白细胞介素17（interleukin 17,IL-17）和血管内皮生长因子（vascular endothelial growth factor,VEGF）的表达水平,探讨鼻息肉 的发生、发展。方法　收集在鼻内镜下慢性鼻-鼻窦炎伴鼻息肉手术患者鼻息肉组织30例,慢性鼻-鼻窦炎不伴鼻息肉手术患者筛窦黏膜组织30例,因鼻中隔偏曲行下鼻甲部分切除术患者下鼻甲黏膜组织10例。采用免疫组织化学SP法检测IL-17、VEGF的表达情况并对两者表达水平相关性进行分析。结果　IL-17、VEGF在鼻息肉组织中的表达明显高于其他两组,两两比较组间差异均具有统计学意义;IL-17与VEGF在鼻息肉组织中的表达呈正相关性。结论　IL-17和VEGF均在鼻息肉组织中的表达增高,对鼻息肉的发生、发展起重要作用;鼻息肉组织中IL-17与VEGF的表达呈正相关,提示两者共同参与鼻息肉的发生与发展。     

催乳素在鼻息肉巨噬细胞中的表达及意义

目的　检测催乳素 (prolactin ,PRL)在鼻息肉和正常鼻黏膜中的表达 ,以探讨PRL在鼻息肉发病过程中可能的作用机制和意义。方法　鼻息肉组织标本来自 2 5例行鼻息肉切除的患者 ,12例行鼾症手术切除的正常下鼻甲组织作为正常鼻黏膜对照。HE染色用于常规组织病理学检查 ,免疫组织化学染色用于观察PRL的表达部位 ,双重免疫组织化学染色用于观察表达PRL的细胞。结果　①与 12份正常下鼻甲组织相比 ,2 5份鼻息肉组织中PRL阳性细胞数 (2 0 5± 0 88)较下鼻甲(0 96± 0 5 0 )中明显增多 ,两者比较差异有显著性 (t =4 0 0 4 ,P <0 0 1)。巨噬细胞 (CD6 8)在鼻息肉组织 (1 85± 0 83)中的表达较下鼻甲组织 (0 93± 0 5 2 )明显增高 ,差异有显著性 (t =3 5 19,P <0 0 1)。②双重免疫组化染色证明PRL表达于巨噬细胞上。结论　PRL通过影响巨噬细胞功能及相关细胞因子的作用 ,间接调整鼻息肉的形成过程     

糖皮质激素对鼻息肉缺氧诱导因子-1α及血管内皮生长因子表达的影响

目的 探讨组织缺氧诱导因子-1α(HIF-1α）及血管内皮生长因子（VEGF）在鼻息肉组织中的表达及相关性, 探讨局部应用糖皮质激素类药物对鼻息肉的作用机制。方法 采用免疫组化SP法检测鼻息肉组织在应用丙酸氟替卡松鼻喷剂治疗前、后及下鼻甲HIF-1α及VEGF的表达变化。结果 鼻息肉组织中HIF-1α和VEGF的表达水平明显高于下鼻甲组织（P均＜0.01）;激素治疗后HIF-1α、VEGF表达下降(P＜0.05)。鼻息肉的发病与组织中HIF-1α、VEGF的表达呈明显正相关（r=0.627, P＜0.05）。结论 局部应用糖皮质激素可降低HIF 1α、VEGF的表达,有效治疗鼻息肉。     

鼻息肉组织中转化生长因子β亚型的表达及意义

目的 探讨转化生长因子β（transforming growth factor,TGF-β)亚型在鼻息肉病患者的息肉组织中的表达和分布，以了解其在上呼吸道慢性炎症过程中的作用。方法 采用免疫组化碱性磷酸酶和抗碱性磷酸酶（alkaline phospatase and anti-alkaline phospatase,APAAP)法检测25例鼻息肉病患者的息肉组织和下鼻甲粘膜中（TGF－β1－3表达，并以8名健康人下鼻甲粘膜作对照。用双重免疫标记法对鼻息肉中的炎细胞进行标记，了解巨噬细胞和嗜酸粒细胞在鼻息肉组织中的数量。用Western免疫印迹法分析TGF－β在鼻息肉中的主要表达亚型。结果 ①TGF－β的表达在鼻息肉病患者的鼻息肉组织中高于下鼻甲粘膜，健康人下鼻甲粘膜中几乎不能检测到；②在TGF－β亚型中可以检测到大量TGF－β，而很少检测到TGF－β2、β3；③鼻息肉组织炎性细胞中嗜酸粒细胞的数量占优势，但TGF－β强阳性表达的细胞中巨噬细胞和嗜酸粒细胞较多。结论 TGF－β1是导致鼻息肉组织中TGF－β强阳性表达的细胞中巨噬细胞和嗜酸粒细胞较多。结论 TGF－β是导致鼻息肉组织中TGF－β家族的优势亚型，巨噬细胞和嗜酸粒细胞是TGF－β的标志细胞。TGF－β1可能是鼻息肉发病的重要因子之一。     

VEGF在伴鼻息肉的慢性鼻-鼻窦炎中的表达及克拉霉素对其的调节作用

目的：探讨血管内皮生长因子（VEGF）在伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）患者鼻黏膜中的表达及克拉霉素对其的调控作用。方法：收集16例CRSwNP组织及21例单纯鼻中隔偏曲患者下鼻甲黏膜,采用实时定量RT-PCR方法检测样本中VEGF的表达。另外收集10例伴鼻息肉的慢性鼻窦炎鼻息肉组织及5例单纯鼻中隔偏曲患者下鼻甲黏膜,采用体外组织块培养及ELISA方法,观察克拉霉素对VEGF表达的调节作用。结果：①VEGF mRNA在CRSwNP组的表达较对照组增高,差异有统计学意义（P〈0.01）;②经克拉霉素刺激前后比较,CRSwNP组织中VEGF蛋白的表达量下降,差异有统计学意义（P〈0.05）。结论：CRSwNP组织中VEGF的表达显著升高,推测VEGF在鼻息肉的发病机制中具有极其重要的作用。克拉霉素可能通过抑制VEGF的表达而达到治疗慢性鼻-鼻窦炎的作用。     

磷酸化信号转导与转录活化因子3和血管内皮生长因子及微血管密度在鼻息肉中的表达及意义

目的:检测磷酸化信号转导与转录活化因子3(p-STAT3)及血管内皮生长因子(VEGF)在鼻息肉组织中的表达和微血管密度(MVD)值,并探讨3者之间在鼻息肉发病过程中的相互关系.方法:选取符合纳入标准的鼻息肉患者手术切除标本30例(鼻息肉组),选取同期单纯行鼻中隔偏曲矫正术中切除的下鼻甲组织10例(对照组).采用免疫组织化学SP法检测鼻息肉组和对照组p-STAT3、VEGF及MVD值.结果:p-STAT3在鼻息肉中黏膜上皮及腺体表达的阳性率为60%,鼻息肉组p-STAT3表达明显高于对照组(P<0.01).VEGF在鼻息肉中黏膜上皮及腺体表达的阳性率为70%,鼻息肉组VEGF表达明显高于对照组(P<0.01).鼻息肉组、对照组中MVD值分别为22.78±7.89、7.12±2.84.p-STAT3在鼻息肉中的表达与VEGF、MVD密切相关,随着p-STAT3强度的增加,VEGF分级及MVD值亦增加.结论:鼻息肉组织中p-STAT3、VEGF与MVD的表达明显增加,且3者之间呈正相关;p-STAT3与鼻息肉的血管生成密切相关,阻断STAT3通路即可阻断血管生成,阻止鼻息肉的形成、发生、发展及复发.     

Toll样受体mRNA在鼻息肉中的表达及意义

目的探讨Toll样受体-2(Toll-like receptor2,TLR-2)及Toll样受体-4(Toll-like receptor-4,TLR-4)mRNA在鼻息肉中的表达,分析TLR-2和TLR-4在鼻息肉发病中的作用。方法应用核酸分子原位杂交技术检测25例鼻息肉患者和20例鼾症患者下鼻甲中TLR-2和TLR-4 mRNA的表达。结果TLR-2和TLR-4 mRNA在25例鼻息肉中均有表达,且分别与对照组间差异有显著性意义。结论TLR-2和TLR-4在鼻息肉中高表达,表明感染性因素仍然是鼻息肉发病中的重要因素。     

鼻息肉中单核细胞趋化蛋白1和血管内皮生长因子的表达

目的明确单核细胞趋化蛋白1（monocyte chemotactic protein 1，MCP-1）和血管内皮生长因子（vascular endothelial growth factor，VEGF）在鼻息肉组织中的表达及其相关性，初步探讨MCP-1与鼻息肉发生的关系。方法取40例鼻息肉组织和25例下鼻甲组织，应用原位杂交和免疫组织化学等方法检测MCP-1和VEGF mRNA及蛋白质的表达。结果鼻息肉组织中MCP-1和VEGF mRNA及蛋白质的表达均高于对照组下鼻甲组织（P值均〈0．01）；鼻息肉组织中MCP-1和VEGF蛋白质的表达呈正相关（r=0．871，P〈0．05）。结论鼻息肉组织中MCP-1和VEGF表达增加，二者协同作用可能是鼻息肉形成的原因之一。     

Hypoxia effects on vascular endothelial growth factor derived epithelial cells of nasal polyps]

OBJECTIVE: To understand the role of nasal mucous epithelial cells to hypoxia in early stage of nasal polyps(NP) formation. METHODS: Epithelial cells of NP and inferior turbinate (IT) were cultured without serum under normal oxygen and hypoxia, and stimulus of inflammatory cytokines. Erythropoietin (EPO) was regarded as hypoxia mark, and expression of vascular endothelial growth factor(VEGF) mRNA and protein derived from epithelial cells were detected respectively by in situ hybridization and ELISA. RESULTS: 1. Under hypoxia, EPO mRNA was expressed intensely in epithelial cells from NP and IT, and there was no significant difference between both of them. This result suggested that EPO might be regarded as a hypoxic mark. 2. The ability of producing VEGF mRNA increased with cytokines stimulation, especially under hypoxia. Protein level of VEGF from epithelial cells of NP and IT increased with cytokines stimulation, especially in hypoxia and was time-dependent. CONCLUSION: Epithelial cells actively produce vast VEGF under hypoxia. The VEGF induced by hypoxia of the mucosa in middle meatus is of importance in the formation of nasal polyps(NP) in early stage, which may be the major cause of NP formation in middle meatus.     

Extracellular matrix components in nasal polyposis

OBJECTIVE: Macroscopically, tissue hydration in nasal polyps seems to be a phenomenon of unknown etiology. As the macromolecular composition of extracellular matrix (ECM) determines to a large extent tissue hydration, which in turn determines tissue volume, we investigated ECM components in nasal polyps (NP) in comparison to nasal mucosa of the inferior turbinate (TM) and sinus mucosa from patients with chronic sinusitis without polyps (CS). MATERIAL AND METHODS: The following parameters were determined: (i) the dry weight of freeze-dried NP, TM and CS; (ii) the total protein content (Bio-Rad Protein Assay) of the tissue; (iii) the quality of proteins, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE); (iv) the amount of albumin, using nephelometry; and (v) the amount of hyaluronic acid, using a chemical method: deaminative hydrolysis with carbazole. RESULTS: In 20 NP we found a significantly elevated total protein content compared to TM (n = 20) and CS (n = 15), referred to 0.1 g dry of tissue. In SDS-PAGE of NP (n = 20) a protein band at approximately 70 kDa, representing albumin, dominated, in comparison to TM. The amount of albumin was significantly increased in NP compared to CS and TM. In contrast, the amount of the glycosaminoglycan, hyaluronic acid, was not elevated in NP or CS. CONCLUSION: Albumin was significantly increased in NP and CS, possibly as a result of inflammatory plasma exudation mechanisms. Hyaluronic acid seems to play no role in the tissue hydration of NP.     

Expression, localization, and significance of vascular permeability/vascular endothelial growth factor in nasal polyps

BACKGROUND: The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. OBJECTIVE: To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. METHODS: Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. RESULTS: The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. CONCLUSION: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.     

Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa

The factors involved in the development of chronic inflammation and edema in nasal polyps remain to be clarified. The expression of vascular endothelial growth factor (VEGF) has been described in plasma cells, suggesting that plasma cells may play a major role in the development of edema in nasal polyps through the production of VEGF. We performed immunohistochemical analysis using specific antibodies to VEGF and to the known VEGF receptors, VEGFR-1 and VEGFR-2, on paraffin sections of human nasal polyps ( n=11) and controls of human mucosa of the normal middle turbinates ( n=6). In normal turbinate mucosa, sporadic immunostaining for VEGF was observed throughout the endothelial cells of the small veins and arteries. VEGFR-1 and VEGFR-2 expression was faint in the healthy turbinates. In nasal polyp tissues, strong immunostaining for VEGF was found in the endothelium of blood vessels and in the infiltrating perivascular inflammatory cells. Fibroblasts also stained for VEGF. Strong immunolabeling to VEGFR-1 was evident in the vascular endothelium, whereas weak to moderate VEGFR-1-staining was generally confined to scattered mononuclear round cells. Mononuclear round cells and the endothelium of capillaries revealed immunoreactivity to VEGFR-2. These findings support a role for VEGF and its receptors, VEGFR-1 and VEGFR-2, in the development and perpetuation of edema and angiogenesis in nasal polyps.     

New immunohistologic findings on the differential role of cyclooxygenase 1 and cyclooxygenase 2 in nasal polyposis

BACKGROUND: Cyclooxygenase 1 (Cox-1) plays a key role in arachidonic acid metabolism and in the pathophysiology and immunology of nasal polyposis in patients suffering from aspirin intolerance. We hypothesize that Cox-2 also might be relevant in the etiology of nasal polyps of aspirin-tolerant patients by their effects on inflammatory mediators as well as on microvascular permeability. METHODS: Fifty-two surgical specimens were immunohistochemically labeled for Cox-1 and Cox-2. Specimens were taken from chronically inflamed mucosa (n = 19) and from nasal polyps (n = 19) during endonasal sinus surgery. Controls were obtained from healthy nasal respiratory mucosa (n = 14), harvested during turbinate surgery in patients with nasal obstruction without inflammatory disease. Staining intensities were semiquantitatively assessed and statistically analyzed. RESULTS: In chronically inflamed tissue the expression of Cox-1 and Cox-2 was strongly labeled. However, in nasal polyps the staining pattern of Cox-1 was similar, but Cox-2 expression in epithelial cells was significantly less than in inflamed, nonpolypous specimens. CONCLUSION: These data suggest that while Cox-1 is strongly up-regulated, Cox-2 expression is significantly lower in epithelial cells of nasal polyps than in those of chronic sinusitis without polyps. The relevance of this finding has to be discussed with respect to the regulatory function of Cox on the inflammatory reaction in nasal respiratory mucosa and its hypothetical role in alterations of capillary permeability via vascular permeability factor/vascular endothelial growth factor.