CD147、CD44和透明质酸与银屑病的相关性研究

发布时间：2018-06-28 15:26

本文选题：银屑病 + CD147　；参考：《河北医科大学》2010年硕士论文

【摘要】： 目的:银屑病(psoriasis, PS)又名“牛皮癣”,是一种常见并易复发的慢性炎症性皮肤病。由于本病发病率较高,易于复发,病程较长,尤以侵犯青壮年为主,故对患者的身体健康和精神影响甚大。表皮增生和真皮乳头层内血管新生是银屑病的主要病理特点。遗传因素和环境刺激是其发病的两大主要因素。银屑病临床表现复杂,为多基因遗传性疾病。其发病涉及到下列4个主要细胞类型:角质形成细胞、淋巴细胞、内皮细胞和中性粒细胞,其中以前二者最为关键。多数学者认为,银屑病是一种T细胞介导的慢性炎症性疾病。银屑病皮损中,表皮和真皮内已证实有活化的T淋巴细胞存在,抑制T细胞活化可能会直接抑制银屑病正常皮肤形成银屑病皮损。银屑病皮损中活化的T细胞可释放炎症因子,如TNF-a、IL-8和INF等,促进银屑病中角质形成细胞的增殖和中性粒细胞的迁移;同时,增生活跃的角质形成细胞能分泌细胞因子,加强T细胞的活化及中性粒细胞的趋化,并形成一个T细胞介导炎症反应的正反馈环路。 CD147分子是一种属于免疫球蛋白超家族的跨膜糖蛋白,是体内外角质形成细胞高增殖和低分化状态的标记分子,已有研究发现CD147与T细胞的发育、分化,特别是活化密切相关。最新研究显示,CD147可能通过刺激透明质酸的分泌诱导CD4十T细胞的活化,CD147能促进单核细胞成熟及巨噬细胞分泌细胞因子,加强炎症组织中单核/巨噬细胞的浸润。CD44是细胞表面的整合膜蛋白,属粘附分子家族,它具有广泛的生物学功能。研究表明CD44S与其它分子配合提供淋巴细胞激活的共刺激信号,尤其是T淋巴细胞及NK等的激活。在激活过程中,CD44扮演“共刺激分子”的角色胞膜上的CD44分子与其配体透明质酸或相应抗体(抗CD44单抗)结合,作为共刺激分子同TCR/CD3复合体接受的刺激一起引起外周血T细胞的增殖,使Th细胞释放IL-2,CTL细胞释放胰蛋白醋酶。为了解银屑病中CD147、CD44的表达以及血中透明质酸的变化,我们利用免疫组化的方法检测了CD147、CD44在银屑病患者及不同病期皮损中的表达,并用放射免疫法测定血中透明质酸的含量,从而探讨它们在银屑病中的作用。方法:皮损标本来源于2006年10月—2009年10月河北医科大学第四医院皮肤科门诊就诊患者,根据临床表现,初诊为银屑病患者,于局麻下在皮损部用环钻取材,立即放入10%甲醛溶液中,石蜡包埋后备用。选取经临床结合组织病理确诊为银屑病患者标本32例,其中男18例,女14例;年龄10-80岁,平均27.2岁。所有患者排除患有其他系统性疾病,且近3个月内未曾接受任何治疗。对照组标本取自河北医科大学第四医院外科20例外伤手术患者的健康皮肤,对照组患者未患其他疾病,且年龄、性别及取材部位与银屑病患者相匹配。组织病理采用石蜡切片HE染色观察,免疫组化采用SP法,染色结果阳性着色为棕黄色颗粒。应用SPSS13.0统计软件分析试验结果。免疫组化结果采用秩和检验Mann-Whitney U检验分析各项指标在PS组和对照组表达情况,CD147与CD44的相关性采用Spearman等级相关分析。结果: 1 CD147在正常皮肤角质形成细胞中和银屑病各组皮损角质形成细胞、T细胞和中性粒细胞中均有表达。在32例银屑病中,阳性表达共26例,其中强阳性8例,阳性、弱阳性各9例,阴性6例。正常对照组中,阴性18例,弱阳性1例,阳性1例,无强阳性表达。结果显示,CD147在银屑病中阳性表达均比正常对照组增高,差异有显著性(P0.05),且在银屑病的进展期表达高于静止期,差异有统计学意义(P0.05)。在不同性别、年龄及病程之间均无显著性差别(P0.05。 2 CD44S在正常人皮肤、寻常型银屑病皮损处及其相邻外观正常皮中均有表达,其中在表皮细胞的棘细胞和基底细胞表面有表达,颗粒层细胞及角质层细胞均无表达,在棘细胞表面的表达最强。真皮组织细胞中CD44S呈均一的表达。在皮肤附属器中的毛囊,小汗腺及血管内皮细胞上均有表达。在32例银屑病患者中,阳性表达24例,其中强阳性5例,阳性9例,弱阳性10例,阴性8例。而对照组20例中仅1例阳性表达,2例弱阳性表达,其余为阴性表达。结果显示,CD44在银屑病中阳性表达均比正常对照组增高,差异有显著性(P0.05),且在银屑病的进展期表达高于静止期,差异有统计学意义(P0.05)。在不同性别、年龄及病程之间均无显著性差别(P0.05)。 3我们以表皮层CD147明确表达阳性的26例标本为阳性组,与另一组6例CD147明确表达阴性的标本为对照组。CD147阳性组的血中透明质酸水平高于对照组。 4 CD147与CD44在银屑病患者同一皮损中的表达相关系数r=0.474,差异有显著性,两者呈正相关。结论:根据实验结果得出以下结论: 1 CD147在银屑病主要表达于角质形成细胞、T细胞和中性粒细胞,并明显高于对照组,且进展期皮损高于静止期。提示银屑病皮损中CD147表达水平增高且与疾病分型和进展程度关联。 2 CD44S在寻常型银屑病表达主要位于表皮细胞的棘细胞和基底细胞,在棘细胞表面的表达最强;真皮组织细胞中CD44S呈均一的表达;在皮肤附属器中的毛囊,小汗腺及血管内皮细胞上均有表达。并明显高于对照组,且进展期皮损高于静止期。提示银屑病皮损中CD44S表达水平增高且与疾病分型和进展程度关联。 3 CD147与CD44呈正相关,提示透明质酸在银屑病中的作用,CD147分泌透明质酸,与其受体CD44S相结合,作为共刺激分子同TCR/CD3复合体接受的刺激一起引起外周血T细胞的增殖。 4银屑病中CD147阳性组的透明质酸值明显高于CD147阴性组,CD147的表达与透明质酸呈正相关,提示CD147的表达与透明质酸生成有关。 5 CD147、CD44S与性别、年龄和病程之间均无相关性。
[Abstract]:Objective: psoriasis (PS), also known as psoriasis, is a common and recurrent chronic inflammatory dermatosis. Due to the high incidence of this disease, it is easy to relapse and has a longer course of disease, especially in the invasion of young and young adults, so it has a great influence on the health and spirit of the patients. Epidermis hyperplasia and dermis papillary neovascularization are psoriasis. The main pathological features. Genetic factors and environmental stimuli are the two major factors of its disease. The clinical manifestations of psoriasis are complex and multigene hereditary diseases. The disease involves the following 4 main cell types: keratinocytes, lymphocytes, endothelial cells and neutrophils, among which the first two are the most important. Most scholars believe that silver is the most important. Crumb disease is a chronic inflammatory disease mediated by T cells. In psoriatic lesions, activated T lymphocytes have been confirmed in epidermis and dermis. Inhibition of activation of T cells may directly inhibit psoriasis and form psoriatic lesions. The activated T cells in psoriatic lesions can release inflammatory factors, such as TNF-a, IL-8 and INF, and promote the development of psoriasis. The proliferation of keratinocytes and the migration of neutrophils in psoriasis; at the same time, the proliferating and active keratinocytes can secrete cytokines, strengthen the activation of T cells and the chemotaxis of neutrophils, and form a positive feedback loop for T cells to mediate the inflammatory reaction.
CD147 is a transmembrane glycoprotein belonging to the superfamily of immunoglobulin, which is a marker for high proliferation and low differentiation of keratinocytes in vitro and in vivo. It has been found that the development and differentiation of CD147 and T cells are closely related to activation. The latest research shows that CD147 may induce the secretion of CD4 ten T by stimulating the secretion of hyaluronic acid. Cell activation, CD147 can promote the maturation of mononuclear cells and the secretion of cytokines by macrophages, and the infiltration of mononuclear / macrophages in the inflammatory tissue is an integrated membrane protein on the surface of the cell, which belongs to the family of adhesion molecules. It has extensive biological functions. The study shows that the co stimulation of CD44S and its molecules provides the co stimulation of lymphocyte activation. Signals, especially the activation of T lymphocytes and NK, in the process of activation, CD44 plays the role of CD44 molecules on the membrane of the role of "co stimulator" with its ligand, hyaluronic acid or corresponding antibody (anti CD44 monoclonal antibody), as a stimulator of the co stimulator and the TCR/CD3 complex to induce the proliferation of the peripheral blood T cells and release the Th cells. IL-2, CTL cells release trypsin of trypsin.
In order to understand the expression of CD147 and CD44 in psoriasis and the change of hyaluronic acid in blood, we detected the expression of CD147, CD44 in psoriatic patients and the skin lesions of different diseases by immunohistochemical method, and measured the content of hyaluronic acid in blood by radioimmunoassay, and thus explored their role in psoriasis.
Methods: the skin lesions were collected from the Department of Dermatology of the Department of Dermatology, Fourth Hospital of Hebei Medical University from October 2006 to October 2009. According to the clinical manifestations, the patients were first diagnosed as patients with psoriasis in the skin lesions under local anesthesia. They were immediately put into the 10% Formaldehyde Solution. The paraffin was embedded after the paraffin embedded. 32 cases of sick patients, including 18 men and 14 women, were 10-80 years old, with an average of 27.2 years old. All patients were excluded from other systemic diseases and had not received any treatment for nearly 3 months. The control group was taken from the healthy skin of 20 cases of surgical trauma surgery in fourth hospital of Hebei Medical University, and the control group had no other diseases, and the year of the control group had no other diseases. The age, sex and location of the material were matched with the patients with psoriasis. The histopathology was observed by HE staining with paraffin section, and the immunohistochemical method was used by SP method. The staining results were stained with brown yellow granules.
SPSS13.0 statistical software was used to analyze the results of the test. The results of immunohistochemistry were analyzed by the rank sum test and Mann-Whitney U test. The expression of each index in the PS group and the control group was analyzed. The correlation between CD147 and CD44 was analyzed by Spearman grade correlation.
Result:
1 CD147 was expressed in the keratinocytes of normal skin and in every group of psoriasis, T cells and neutrophils. In 32 cases of psoriasis, positive expression was 26 cases, of which 8 cases were positive, 9 cases were positive, 9 cases were weak positive and 6 cases were negative. In normal control group, 18 cases were negative, 1 cases were weakly positive, 1 cases positive, no strong positive expression. The results showed that the positive expression of CD147 in psoriasis was higher than that in the normal control group (P0.05), and the expression in the progression of psoriasis was higher than that in the stationary phase (P0.05). There was no significant difference between the sexes, age and course of disease (P0.05.
2 CD44S was expressed in normal skin, skin lesions of psoriasis vulgaris and its adjacent normal skin, which expressed on the surface of the spinous cells and basal cells of epidermal cells, the granular layer cells and the keratinocytes were not expressed, and the expression of CD44S was the strongest in the surface of the spinous cells. In 32 cases of psoriasis, there were 24 positive expressions in 32 cases of psoriasis. Among them, there were 5 cases of strong positive, 9 positive, 10 weak positive and 8 negative. Only 1 of the 20 cases in the control group were positive, 2 weak positive and other negative expression. The results showed that the positive expression of CD44 in psoriasis was all compared to the positive expression of psoriasis. In the normal control group, the difference was significant (P0.05), and the expression in the progression of psoriasis was higher than that in the stationary phase. The difference was statistically significant (P0.05). There was no significant difference between different sex, age and course of disease (P0.05).
3 of the 26 specimens with positive expression of CD147 in the epidermis, the positive group was positive, with the other 6 cases of CD147 clearly expressed as negative, the level of hyaluronic acid in the blood of the.CD147 positive group was higher than that of the control group.
4 the correlation coefficient r=0.474 between CD147 and CD44 in psoriasis patients with the same lesion was significantly different, and there was a positive correlation between them.
Conclusion: according to the results of the experiment, the following conclusions are drawn.
1 CD147 was mainly expressed in keratinocytes, T cells and neutrophils in psoriasis, which was significantly higher than that in the control group, and the progressive lesion was higher than that in the stationary phase. It was suggested that the level of CD147 expression in psoriatic lesions was higher and associated with the classification and progression of the disease.
The expression of 2 CD44S in psoriasis vulgaris mainly lies in the spinous cells and basal cells of the epidermal cells, the strongest expression on the surface of the spinous cells, the expression of CD44S in the dermal tissue cells, the follicles in the skin appendages, the small sweat glands and the vascular endothelial cells, which are obviously higher than those in the control group, and the progressive skin lesions are higher than the rest. It was suggested that the expression of CD44S in psoriatic lesions was increased and correlated with the classification and progression of psoriasis.
3 CD147 has a positive correlation with CD44, suggesting the role of hyaluronic acid in psoriasis, CD147 secretion of hyaluronic acid, and its receptor CD44S, as a stimulator that CO stimulates the proliferation of T cells in peripheral blood together with the stimulation of the TCR/CD3 complex.
The hyaluronic acid value of CD147 positive group in 4 psoriasis was significantly higher than that of CD147 negative group. The expression of CD147 was positively correlated with hyaluronic acid, suggesting that the expression of CD147 was related to hyaluronic acid production.
5 there was no correlation between CD147, CD44S and sex, age and duration.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R758.63

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