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。     

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.     

Hypoxia stimulates inflammatory and fibrotic responses from nasal-polyp derived fibroblasts

OBJECTIVES/HYPOTHESIS: Chronic sinusitis is primarily an inflammatory disorder characterized by hyperplasia of immune cells and sinus tissue. Nasal mucosal swelling or polyps can occlude the sinus ostia, decreasing the level of oxygen available to the sinus tissue. Hypoxia in many diseases results in increased recruitment of inflammatory cells and release of cytokines. The role of hypoxia in chronic sinusitis is unknown. We hypothesized that hypoxia induces production of mediators that recruit cells into the sinus tissue and are involved in remodeling of the nasal mucosa. METHODS: We compared data from unstimulated nasal-polyp derived fibroblasts with those cultured in hypoxic (10% O2) and anoxic (0% O2) environments. Changes in mRNA expression and protein levels of cytokines and chemokines were measured along with changes in cellular proliferation. RESULTS: Hypoxic conditions did not change the proliferative capacity of fibroblasts, whereas anoxia led to a 40% reduction in cellular proliferation (P < .05). Hypoxia led to increases in secretion of many cytokines including vascular endothelial growth factor and CCL11. As a marker of remodeling, procollagen and fibronectin production were significantly increased under hypoxic conditions. CONCLUSIONS: Hypoxic conditions present in the sinus tissue could increase production of proinflammatory and remodeling cytokines that contribute to the inflammation observed in sinusitis. Surgical intervention may help decrease inflammation by allowing reoxygenation of the sinus cavity and decrease the hypoxic induction of cytokines and remodeling factors.     

转化生长因子β受体Ⅰ型及Ⅱ型在慢性鼻-鼻窦炎和鼻息肉组织中的表达

目的:探讨转化生长因子β受体(TGFβR)Ⅰ型及Ⅱ型在慢性鼻-鼻窦炎、鼻息肉及正常下鼻甲组织中表达的差异性,以及Ⅰ、Ⅱ型受体在慢性鼻窦炎、鼻息肉发病机制中可能的作用。方法:采用免疫组织化学方法检测TGFβRⅠ、TGFβRⅡ在25例慢性鼻-鼻窦炎、21例鼻息肉、17例下鼻甲组织中的表达,并比较TGFβRⅠ、TGFβRⅡ在慢性鼻-鼻窦炎、鼻息肉、正常下鼻甲组织中表达的差异。结果:TGFβRⅠ、TGFβRⅡ表达的平均灰度值在正常下鼻甲黏膜分别为175.78±7.06、165.00±1.79;在慢性鼻-鼻窦炎组织中分别为147.33±8.15、147.77±4.62;而在鼻息肉组织中分别为125.91±11.26、129.82±1.46。慢性鼻-鼻窦炎及鼻息肉组织中TGFβRⅠ、TGFβRⅡ的表达均比正常下鼻甲黏膜中的表达高,均差异有统计学意义(均P<0.01);且TGFβRⅠ、TGFβRⅡ在鼻息肉组织中的表达比在慢性鼻-鼻窦炎病变黏膜中的表达高,均差异有统计学意义(均P<0.01)。结论:TGFβRⅠ、TGFβRⅡ在慢性鼻-鼻窦炎、鼻息肉组织中具有不同的表达水平及分布特点,提示其可能在慢性鼻-鼻窦炎、鼻息肉的发生发展过程中发挥不同的作用。     

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.     

转化生长因子β1和基质金属蛋白酶及其组织抑制物在慢性鼻窦炎和鼻息肉组织中的差异性表达

目的:探讨转化生长因子β1(TGF-β1),基质金属蛋白酶1、7、9(MMP-1、7、9)及其组织抑制物-1(TIMP-1)在慢性鼻窦炎和鼻息肉以及正常下鼻甲黏膜组织中表达程度的差异。方法:采用酶联免疫吸附试验(ELISA)检测22例慢性鼻窦炎筛窦黏膜、21例鼻息肉和15例下鼻甲黏膜组织中TGF-β1,MMP-1、7、9以及TIMP-1的蛋白表达量,并比较他们在不同组织中表达程度的差异。结果:①TGF-β1、MMP-7、MMP-9及TIMP-1在慢性鼻窦炎和鼻息肉组织中的表达均比正常下鼻甲黏膜组织增高,差异具有统计学意义(均P<0.05);②慢性鼻窦炎组织中TGF-β1和TIMP-1相比鼻息肉组织中的表达增高,差异具有统计学意义(P<0.01和P<0.05);③鼻息肉组织中MMP-7的表达比慢性鼻窦炎组织中的表达增高,差异具有统计学意义(P<0.01)。结论:慢性鼻窦炎和鼻息肉组织显示出不同的TGF-β1、MMP-7、TIMP-1蛋白表达水平。     

布地奈德对鼻息肉组织中水通道蛋白-3表达的影响

目的探讨鼻腔局部应用布地奈德喷雾剂（BUD）对鼻息肉组织中水通道蛋白-3表达的影响及糖皮质激素治疗鼻息肉的作用机制。方法46例慢性鼻窦炎鼻息肉Ⅱ型患者治疗前后取鼻息肉组织,采用免疫组化技术检测组织标本Aquaporin-3（AQP-3）的表达情况,比较分析组间差异。结果布地奈德治疗后鼻息肉组织（治疗组）中AQP-3的表达数在上皮下间质的腺体细胞及血管内皮细胞中较未治疗组（对照组）显著下降（P〈0．01）,而黏膜上皮细胞表达数较未治疗组中提高（P〈0．01）。结论在布地奈德作用下鼻息肉组织水肿减轻,体积缩小与组织中水通道蛋白-3在上皮下间质的腺体细胞及血管内皮细胞中表达减少有关。     

Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non-asthmatic patients

The cause of nasal polyps remains unknown, although there is a well-recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty-four asthmatic and 35 non-asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.     

血管内皮生长因子在鼻息肉组织中的表达和意义

目的探讨血管内皮生长因子(vascular endothelial growth factor, VEGF)在鼻息肉组织中的表达及其在鼻息肉发病中的意义。方法将鼻息肉患者分为A、B 组,A组为Ⅱ型1、2期患者,B组为Ⅱ型3期及Ⅲ型患者。另有20例鼻中隔偏曲患者的正常下鼻甲组织作对照组。采用免疫组化SP法检测三组VEGF的表达。结果正常鼻黏膜中VEGF的染色呈弱阳性,而在A、B组鼻息肉组织中VEGF的阳性率明显高于对照组,B组中阳性率和阳性细胞数均高于A组;VEGF在鼻息肉组织中主要定位于基底膜周围的炎性细胞和上皮细胞以及腺体、血管周围和血管壁内皮细胞。结论VEGF通过在鼻息肉组织中过度表达促进息肉组织内的血管增殖和炎性细胞聚积,促进鼻息肉的发生发展。     

Immunohistochemical localization of eotaxin immunoreactivity in nasal polyps

Eotaxin is a C-C chemokine that acts to selectively induce local accumulation of eosinophils and basophils. Eotaxin is also believed to be involved in the infiltration of eosinophils in the nasal polyps of patients with chronic sinusitis. However, only a few studies on eotaxin in nasal polyps have been performed. In this study, we investigated the localization of eotaxin in human nasal polyps and the identification of eotaxin-positive cells using immunohistochemistry. The distribution of eotaxin immunoreactivity in the nasal polyps of patients with chronic sinusitis was found to almost coincide with the presence of eosinophils. Eotaxin immunoreactivity was also detected in some vascular endothelial cells. These findings suggest that eotaxin is produced by eosinophils and vascular endothelial cells in nasal polyps and is involved in the accumulation of eosinophils in nasal polyps.     

Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non‐asthmatic patients

The cause of nasal polyps remains unknown, although there is a well‐recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty‐four asthmatic and 35 non‐asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.     

European position paper on rhinosinusitis and nasal polyps 2007

Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.     

优质护理应用于鼻内镜下手术治疗鼻窦炎鼻息肉中的价值研究

目的观察优质护理应用于鼻内镜下手术治疗鼻窦炎鼻息肉中的价值。方法选取2018年4月~2019年4月在我院就诊的68例鼻内镜下手术治疗的鼻窦炎鼻息肉患者,随机分为优质护理的观察组与常规护理的对照组,各34例。结果与对照组相比,观察组并发症发生率低,术后恢复时间短,P<0.05,具有统计学意义。结论给予鼻内镜下手术治疗的鼻窦炎鼻息肉患者优质护理,能降低并发症发生率,促进术后恢复,值得借鉴。     

金黄色葡萄球菌超抗原与慢性鼻窦炎鼻息肉发生相关性的研究

目的:探讨金黄色葡萄球菌(金葡菌)超抗原在鼻息肉发生中的作用。方法:对42例双侧鼻息肉患者(鼻息肉组)、27例单纯慢性鼻窦炎患者(鼻窦炎组)和12例无鼻窦疾病史的鼻外伤患者(对照组)的鼻腔分泌物进行细菌培养;采用酶联免疫吸附试验(ELISA)法检测各组患者的鼻黏膜或息肉组织中的金葡菌超抗原;在组织学上,对苏木精-伊红染色切片进行嗜酸粒细胞计数。结果:鼻腔分泌物中金葡菌阳性率鼻息肉组为7.1%,鼻窦炎组为3.7%,对照组为0,各组间差异均无统计学意义(均P>0.05)。ELISA结果显示:鼻息肉组金葡菌超抗原阳性率为54.76%,鼻窦炎组和对照组阳性率均为0。嗜酸粒细胞计数平均值:鼻息肉组23.94±13.88,鼻窦炎组0.29±0.51,对照组0.08±0.28,3组间均差异有统计学意义(均P<0.05)。鼻息肉组中ELISA结果阳性者嗜酸粒细胞水平比阴性者高,但差异无统计学意义(P>0.05)。结论:金葡菌超抗原与鼻息肉的发生存在相关性,有可能在鼻息肉的致病机制中起重要作用。     

鼻息肉中血管内皮生长因子mRNA的检测与意义

目的 :检测鼻息肉组织和鼾症下鼻甲粘膜组织中的血管内皮生长因子 (VEGF) m RN A水平的表达 ,了解其在慢性炎症过程中的作用。方法 :取 6例行下鼻甲切除术的下鼻甲粘膜和 7例鼻息肉切除术的鼻息肉标本 ,用半定量的反转录 -聚合酶链反应 (RT- PCR)方法检测 VEGF的 m RNA表达。结果 :RT- PCR结果显示在鼻息肉组织中 V EGF的表达较鼾症患者下鼻甲粘膜组织明显升高。结论 :鼻息肉组织中 VEGF的表达显著升高 ,推测 VEGF在鼻息肉的形成、生长及复发过程中具有极其重要的作用。     

Evidence of platelet-activating factor in nasal polyps.

Platelet-activating factor (PAF) was measured in human nasal polyps obtained from patients with chronic sinusitis. PAF was quantitated by platelet-aggregating activity and was found to be 7.8 +/- 1.8 pg/micrograms phosphorus of polyp phospholipid (mean +/- SE; n = 23). In the polyps, phosphatidylcholine constituted 30% of the total phospholipids, of which 8.5% was the ether-linked type. Incubations of replicates of the fresh polyps in Tyrode's solution in the presence of calcium ionophore A23187 and antihuman immunoglobulin E resulted in 295 and 65% increases in the amount of PAF, respectively. Thus, nasal polyps in humans with chronic sinusitis possess PAF and have the potential to produce PAF upon stimulation. The participation of PAF in nasal polyp formation is discussed.     

Dual action of TGF-beta1 on nasal-polyp derived fibroblasts

OBJECTIVES: Transforming growth factor beta-1 (TGF-beta1) is a known fibrogenic factor with immunosuppressive properties. We wanted to determine the effect of stimulation with TGF-beta1 on nasal polyp-derived fibroblasts and assess the role this molecule would have in polyp formation and growth. STUDY DESIGN: Nasal-polyp derived fibroblasts were cultured with or without TGF-beta1, and proliferation and cytokine secretion were measured. METHODS: Fibroblasts were isolated from nasal polyps following endoscopic surgery. Cells were plated and grown until confluent, after which they were split and used in assays. Cells were stimulated with TGF- beta1 and mRNA collected after 16 hours, supernatants after 72 hours, and proliferation measured after 96 hours of culture. RESULTS: TGF-beta1 significantly (P < .02) increased proliferation of nasal-polyp derived fibroblasts. We examined the expression of inflammatory cytokines and found that TGF-beta1 decreased expression of CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), granulocyte-colony stimulating factor (G-CSF), and GM-CSF (P < .05). In contrast, incubation with TGF-beta1 increased fibronectin, procollagen, vascular endothelial growth factor (VEGF), and TGF-beta2 protein production (P < .05). For select samples, we confirmed that the increased protein production was due to increased mRNA expression. CONCLUSION: These studies suggest that TGF-beta1 expression in polyp tissue can have dual effects. One role is to act as an anti-inflammatory agent shown by the ability to inhibit pro-inflammatory mRNA and protein production. At the same time, TGF-beta1 expression leads to increases in factors involved in fibrosis and angiogenesis, promoting remodeling and cell growth.