| Nasal polyps (NP) is the most common disease in otolaryngology-head and neck surgery, and the etiology and pathogenesis of NP are not clear. The conventional wisdom is that the forming of NP is concerned with chronic infection of nasal mucosa and allergy, but all these viewpoints can't explain why NP occur at ostiomeatal complex but not inferior turbinate and inferior meatus who stand in the forefront of nasal cavity. With the development of immunology and molecular biology, various factors are thought to be coefficient for resulting in NP. NP is a kind of chronic inflammatory disease, now many people consider that NP is related to circumstance of middle meatus. Dr. Ohnishi(1992)speculated that the low blood in middle meatus might be responsible for the forming of NP, this doctrine will provide a new way for exploring the pathogenesis of nasal polyps.The anatomical structure characteristics of ostiomeatal complex and changes of congenital or acquired in the nose can cause micro-environment hypoxia; Local inadequate drainage or infection caused chronic nasal inflammation; Nasal inflammation also resulted in the further reduction of blood flow .The results will inevitably lead to local tissue ischemia and hypoxia, so what impact did these factors done on the nasal epithelial cells, and what consequences will these effects have?Because of less distribution of blood vessels in the middle meatus of nasal cavity, we speculated that there maybe exists a tissue hypoxia microenvironment. In addition to hypoxia, infection and inflammation also act at local tissue, so we consider that these three factors are the most important to the happen of NP.Mucosal epithelial cells of the respiratory tract is the sentinel cells that generated immune response against the antigen or pathogenic microorganisms, and that played a critical role in the pathogenesis of respiratory diseases. We also confirmed that nasal epithelial cells have very active immune activity in previous studies and can synthesize or secret many cytokines. The VEGF is one of the most potent vascular permeability agents, and its expression may be induced by the hypoxia and inflammatory cytokines. HIF-1 is an important transcription factor for hypoxia adaptation that was founded in recent years; HIF-1 is also the core control factor of angiogenesis under hypoxic condition. HIF-1 directly involved in the entire process of angiogenesis by influencing the expression of other factors. HIF-1 is composed of HIF-1αand HIF-1β.When HIF-1αlevels increase in response to hypoxia in tissue, functional HIF-1 regulates transcription at HREs of target gene regulatory sequences, which results in the transcription of genes such as VEGF.Epithelium is regarded as an active biological barrier, and it modulates inflammation of tract. With the development of nasal disease research in recent years,more and more research objectives was locked on nasal epithelial cells. Under the hypoxia of local tissue, the epithelial cells respond to immunoreactions and generate a series of active mediators HIF-1 and VEGF as the first line of respiratory natural immunity defense. VEGF may increase specific permeability on the capillaries and small veins by the endothelial cells vesicles, and then macromolecular material easily penetrates the vascular wall; plasma exuded; extracellular fluid increases and tissue edemas. Our previous studies confirmed that the expression of VEGF in the nasal polyps was significantly stronger than in the inferior turbinate, and the edema of nasal polyps mainly caused by VEGF. HIF-1 is directly involved in the entire process of angiogenesis by influencing the expression of other factors. At present, studies has been founded that body regulateed the EPO and VEGF gene expression by increasing the level of HIF-1 in tumor tumorigenesis and hypoxia conditions. HIF-1 plays a key role in Body tolerancing hypoxic environment and the occurrence and metastasis of tumor. But what is the mechanism of HIF-1αin nasal polyps inflammatory environment? EPO is an oxygen-sensitive protein that is extremely sensitive to hypoxia. Hypoxia can induce organizations to produce large plenty of EPO.EPO was considered as hypoxia marker in our experiment. We discussed the major significance of HIF-1αand VEGF who were induced by the lack of oxygen, infection factors and inflammatory cytokine in the formation of nasal polyps, and the inhibition effect of dexamethasone on human nasal epithelial cells releasing cytokines .Methods Nasal mucosa were obtained from 22 patients with nasal polyps undergoing polypectomy and 8 patients with obstructive sleep apnea syndrome subjected to partial inferior turbinectomy, Which had not been treated with corticosteroids. In the first part of the article, the expression of HIF-1αand VEGF protein and mRNA derived from nasal polyp tissues was detected by immunocytochemistry and in situ hybridization. In the second part of the article, we isolated HNEC, and epithelial cells of nasal polyps (NP) and inferior turbinate (IT) were cultured without serum under stimulus of hypoxia,LPS 10, 100, 1000ng/ml,IL-Iβ20ng/ml and LPS 100ng/ml+dexamethasone 13ng/ml for 3h,6h and 9h, respectively. The expression of HIF-1αand VEGF protein and mRNA derived from epithelial cells was detected by in situ hybridization and western blot.Results①The expression of HIF-1αand VEGF expressed more intensively in tissues from NP than IT(P<0.05).②Under hypoxia, EPO mRNA was expressed intensely in epithelial cells from NP and IT, and there was nosignificant difference between both of them. This result suggested that EPO might beregarded as a hypoxic mark;③The expression of HIF-1αand VEGF increased under the stimulus of inflammatory factor and hypoxia with the increasing of time and concentration, especially in LPS 100ng/m(lP<0.05);④The expression of HIF-1αand VEGF expressed more intensively in epithelial cells from NP than IT under three conditions above.(P<0.05);⑤t he expression of HIF-1αand VEGF was positive correlation (r=0.870).⑥The HIF-1αand VEGF level decreased under the stimulus of LPS 100ng/ml + dexamethasone 13 ng/ml when compared with the stimulus of LPS100ng/ml(P<0.05).Conclusion On the basis of the above results, epithelial cells actively produce vast HIF-1αand VEGF under inflammatory factor and hypoxia. HIF-1αand VEGF were involved in the formation of nasal polyps. dexamethasone can suppress them fiercely. We confirm that NP is the end of chronic inflammation leaded by many mechanisms.
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