MMP-7、TGF-β1及PAI-1在鼻息肉中的表达及其病理意义

发布时间：2018-01-24 01:07

本文关键词： 免疫组化鼻息肉 MMP-7 TGF-β1 PAI-1　出处：《郑州大学》2010年硕士论文　论文类型：学位论文

【摘要】： 鼻息肉是最常见的上呼吸道慢性炎症性疾病之一,其病因及发病机制被大多数学者认为是多因素多步骤的过程,与感染、免疫及细胞因子有关。鼻息肉的具体发病机制尚不完全清楚,但呼吸道黏膜的损伤-修复和结构重塑已经被证实在鼻息肉的发病机制中起关键作用,而细胞外基质的合成和降解是组织结构重塑中最关键的一步。为此我们检测与组织结构重塑及基底膜合成和降解过程密切相关的基质金属蛋白酶-7、转化生子因子-β1及纤溶酶原激活物抑制剂-1在鼻息肉及正常下甲黏膜中的表达水平,以探讨其在鼻息肉形成过程中发挥的作用。材料和方法 1.临床资料：鼻息肉标本50例,均为2008年7月-2009年7月在郑州大学一附院接受鼻内镜鼻窦手术的患者。选择标准：单侧或者双侧鼻窦CT检查阳性,鼻内镜检查或手术中发现息肉。所有患者临床病例资料完整,均无变应性鼻炎,支气管哮喘,阿司匹林耐受不良及其他系统性疾病,且在术前一月内未使用过激素或抗组胺类药物。下鼻甲粘膜标本30例,均为2008年7月-2009年7月在郑州大学一附院接受鼻内镜手术的鼻中隔偏曲患者,取之对侧代偿性肥大的下甲。 2.实验方法：对50例鼻息肉组织和30例下鼻甲粘膜组织进行HE染色,并用免疫组化SP法检测上述标本中MMP-7、TGF-β1及PAI-1蛋白的表达。 3.结果判定：三种蛋白质均以胞质呈现棕黄色或者棕褐色染色为阳性细胞。取染色良好(特异性染色清晰,背景染色低)的组织切片,根据染色细胞不同的染色强度和高倍镜下阳性细胞数百分比作为依据,其两者相乘,结果大于3分极为免疫反应阳性,进行结果的判定。 4.统计学分析：应用SPSS11.0统计软件行卡方检验(x2检验)进行显著性检验,相关分析应用列联表的关联性分析,检验标准α=0.05。结果 1.HE染色光镜下见细胞核染色为蓝色、蓝黑色或者深蓝色,而胞浆呈现为淡粉色或者是淡红色。可见鼻息肉组织由极度水肿的疏松结缔组织构成,表面覆盖呼吸上皮,大量杯状细胞增生,其表面没有纤毛,腺体组织增生明显,多为长管状或囊性扩张,没有真正的浆液黏液腺,间质中有大量炎性细胞浸润,主要为嗜酸性粒细胞,肥大细胞的数量也明显增加,基底膜增厚,血管通透性增高,没有神经组织。而在下鼻甲黏膜组织中见到的腺管多呈圆形,间质中炎症细胞浸润较少,几乎见不到嗜酸性粒细胞。 2.MMP-7的阳性产物主要定位于细胞浆中,呈棕黄或者棕褐色,光镜下可见其广泛表达在鼻息肉组织中的上皮细胞、血管内皮细胞、腺体细胞以及间质内浸润的炎症细胞的胞浆内,在基质中也有表达。MMP-7其在鼻息肉中的阳性表达率为42.00%。而在对照组正常下甲粘膜中的阳性率为3.33%。两者表达结果经统计学分析显示,p值少于0.05,说明其在鼻息肉及下甲组织中表达的差异具有统计学意义。 3.TGF-β1的阳性产物主要定位于细胞浆中,呈棕黄或者棕褐色,光镜下可见其广泛表达在鼻息肉组织中的上皮细胞、血管内皮细胞、腺体细胞以及间质内浸润的炎症细胞的胞浆内,在基质中也有表达。其在鼻息肉中的阳性表达率为72.00%。TGF-β1在对照组下鼻甲粘膜组织中的阳性率为13.33%。两者表达结果经统计学分析显示,p值少于0.05,说明其在鼻息肉及下甲组织中的表达的差异具有统计学意义 4.PAI-1的阳性产物主要定位于细胞浆中,呈棕黄或者棕褐色,光镜下可见其广泛表达在鼻息肉组织中的上皮细胞、血管内皮细胞、腺体细胞以及间质内浸润的炎症细胞的胞浆内,在基质中也有表达。其在鼻息肉及对照组中的阳性表达率分别为18.00%和0.00%。两者表达结果经统计学分析显示,p值少于0.05,说明其在鼻息肉及下甲组织中的表达的差异具有统计学意义。 5.MMP-7蛋白表达阳性病例中,TGF-β1蛋白表达阳性率为90.00%,MMP-7蛋白表达阴性病例中TGF-β1蛋白表达阳性率60.00%,经统计学分析,结果显示列联系数r=0.311,p=0.0210.05,两种蛋白在鼻息肉组织中的表达有关联性。 6.MMP-7蛋白表达阳性病例中,PAI-1蛋白表达阳性率为40.00%,MMP-7蛋白表达阴性病例中PAI-1蛋白表达阳性率20.00%,经统计学分析,结果显示p0.05,两种蛋白在鼻息肉组织中的表达无关联性。 7.TGF-β1蛋白表达阳性病例中,PAI-1蛋白表达阳性率为30.56%,TGF-β1蛋白表达阴性病例中PAI-1蛋白表达阳性率0.00%,经统计学分析,结果显示列联系数r=0.314,p0.05,两种蛋白在鼻息肉组织中的表达有关联性。结论 1.异常增高的MMP-7,TGF-β1及PAI-1可使组织基底膜发生变化,参与鼻息肉的组织结构重塑。 2.MMP-7、TGF-β1及PAI-1参与了鼻息肉的形成过程,但是与其临床分型、患者的性别和年龄无关。
[Abstract]:Nasal polyps is one of the most common upper respiratory tract of chronic inflammatory disease, its etiology and pathogenesis by most scholars is a process of multiple factors and steps, and the infection, immunity and cytokines. The pathogenesis of nasal polyps is not completely understood, damage repair and remodeling of airway mucous membrane but has been that play a key role in the pathogenesis of nasal polyps, and the synthesis and degradation of extracellular matrix is the most critical step in tissue remodeling. Therefore we detected and tissue remodeling and basement membrane synthesis and degradation of matrix metalloproteinase is closely related to the -7, transforming growth factor beta 1 and plasminogen activator inhibitor -1 in nasal polyps and normal mucosa in a expression level, to explore the formation process play a role in nasal polyps.
Materials and methods
1. clinical data:
50 cases of nasal polyp specimens were in July 2008 -2009 year in July received endoscopic sinus surgery in the First Affiliated Hospital of Zhengzhou University. The patient selection criteria: unilateral or bilateral nasal polyps found CT positive, nasal endoscopy or surgery. All cases of patients with complete data, there were no allergic rhinitis, bronchial asthma, aspirin intolerance and other systemic diseases, and in the preoperative January in not using hormones or antihistamine drugs. 30 cases of inferior turbinate mucosa specimens were in July 2008 -2009 year in July received endoscopic sinus surgery in the First Affiliated Hospital of Zhengzhou University, the deviation of nasal septum were taken from contralateral compensatory hypertrophy under armour.
2. the method of experiment:
50 cases of nasal polyps and 30 cases of inferior turbinate mucosa were stained with HE, and the expression of MMP-7, TGF- beta 1 and PAI-1 protein in the above specimens were detected by immunohistochemical SP method.
3. the results are as follows:
Three proteins in the cytoplasm showed brown or brown staining in the cell. Good staining (specific staining clear, low background staining) tissue sections, according to the staining intensity of stained cells at high magnification and different number of positive cells percentage as the basis, the two multiplied by more than 3 points for immune results the positive reaction, to determine the results.
4. statistical analysis:
The SPSS11.0 statistical software was used for the saliency test (x2 test), the correlation analysis was applied to the correlation analysis of the contingency table, and the standard alpha =0.05. was tested.
Result
1.HE staining under light microscope nuclear staining is blue, dark blue or dark blue, and the cytoplasm is pink or reddish. Visible nasal polyps composed of loose connective tissue extreme edema, covering the surface of the respiratory epithelium, a large number of goblet cell hyperplasia, there is no cilia on the surface of glandular tissue, hyperplasia, mostly long or cystic dilatation, no real serous mucinous, interstitial inflammatory cell infiltration, mainly for eosinophils, mast cells also increased, basement membrane thickening, increased vascular permeability, no nerve tissue. And see in the inferior turbinate mucosa of the glandular tube round and less infiltration of inflammatory cells in the stroma, almost no eosinophils.
The positive products of 2.MMP-7 mainly located in the cytoplasm, showed brown or tan, under light microscope, which are widely expressed in nasal polyps epithelial cells, vascular endothelial cells, glandular cells and inflammatory cells infiltration in interstitial cytoplasm, in the matrix also has the expression of.MMP-7 positive expression in the nose polyps in the rate of 42.00%. in the positive rate of the control group under a normal mucosa. The results by statistical analysis showed the expression of 3.33%., P value of less than 0.05, indicating the significant difference in its expression in nasal polyps and a tissue.
Positive products of 3.TGF- beta 1 is mainly located in the cytoplasm, showed brown or tan, under light microscope, which are widely expressed in nasal polyps epithelial cells, vascular endothelial cells, glandular cells and inflammatory cells infiltration in interstitial cytoplasm, in the matrix also has expressed its positive expression. In nasal polyps was the positive rate of 72.00%.TGF- beta 1 in the control group under the turbinate mucosa tissues for the expression of 13.33%. results by statistical analysis showed that the p value is less than 0.05, indicating the significant difference in its expression in nasal polyps and under armour in the organization
The positive products of 4.PAI-1 mainly located in the cytoplasm, showed brown or tan, under light microscope, which are widely expressed in nasal polyps epithelial cells, vascular endothelial cells, glandular cells and inflammatory cells infiltration in interstitial cytoplasm, in the matrix are expressed. The positive expression in the nose the polyps in the control group were statistical analysis results showed that the expression of both 18% and 0.00%., P value of less than 0.05, indicating the significant difference in its expression in nasal polyps and Xiajia tissues.
The positive expression of 5.MMP-7 protein beta 1 cases, TGF- positive expression rate was 90%, negative cases of TGF- beta 1 protein expression rate of MMP-7 protein expression in 60%, by statistical analysis, results showed that the column connection number r=0.311, p=0.0210.05, two kinds of protein in nasal polyps of relevance.
The positive rate of PAI-1 protein expression was 40% in 6.MMP-7 protein positive cases. The positive rate of PAI-1 protein expression was 20% in negative cases of MMP-7 protein expression. After statistical analysis, the results showed that there was no correlation between the expression of P0.05 and two proteins in nasal polyps.
The positive expression of 7.TGF- protein beta 1 cases, the positive rate of PAI-1 expression was 30.56%, 1 protein expression of TGF- beta PAI-1 protein expression positive rate of 0% negative cases, through statistical analysis, results showed that the column connection number r=0.314, P0.05, the expression of two proteins in nasal polyps have relevance.
conclusion
1. the abnormal increase of MMP-7, TGF- beta 1 and PAI-1 can change the tissue basement membrane and participate in the remodeling of the tissue structure of nasal polyps.
2.MMP-7, TGF- beta 1 and PAI-1 are involved in the formation of nasal polyps, but their sex and age are not related to their clinical typing.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R765.25

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