本文選題：銀屑病 + CD147��； 參考：《河北醫(yī)科大學(xué)》2010年碩士論文

【摘要】： 目的:銀屑病(psoriasis, PS)又名“牛皮癬”,是一種常見并易復(fù)發(fā)的慢性炎癥性皮膚病。由于本病發(fā)病率較高,易于復(fù)發(fā),病程較長(zhǎng),尤以侵犯青壯年為主,故對(duì)患者的身體健康和精神影響甚大。表皮增生和真皮乳頭層內(nèi)血管新生是銀屑病的主要病理特點(diǎn)。遺傳因素和環(huán)境刺激是其發(fā)病的兩大主要因素。銀屑病臨床表現(xiàn)復(fù)雜,為多基因遺傳性疾病。其發(fā)病涉及到下列4個(gè)主要細(xì)胞類型:角質(zhì)形成細(xì)胞、淋巴細(xì)胞、內(nèi)皮細(xì)胞和中性粒細(xì)胞,其中以前二者最為關(guān)鍵。多數(shù)學(xué)者認(rèn)為,銀屑病是一種T細(xì)胞介導(dǎo)的慢性炎癥性疾病。銀屑病皮損中,表皮和真皮內(nèi)已證實(shí)有活化的T淋巴細(xì)胞存在,抑制T細(xì)胞活化可能會(huì)直接抑制銀屑病正常皮膚形成銀屑病皮損。銀屑病皮損中活化的T細(xì)胞可釋放炎癥因子,如TNF-a、IL-8和INF等,促進(jìn)銀屑病中角質(zhì)形成細(xì)胞的增殖和中性粒細(xì)胞的遷移;同時(shí),增生活躍的角質(zhì)形成細(xì)胞能分泌細(xì)胞因子,加強(qiáng)T細(xì)胞的活化及中性粒細(xì)胞的趨化,并形成一個(gè)T細(xì)胞介導(dǎo)炎癥反應(yīng)的正反饋環(huán)路。 CD147分子是一種屬于免疫球蛋白超家族的跨膜糖蛋白,是體內(nèi)外角質(zhì)形成細(xì)胞高增殖和低分化狀態(tài)的標(biāo)記分子,已有研究發(fā)現(xiàn)CD147與T細(xì)胞的發(fā)育、分化,特別是活化密切相關(guān)。最新研究顯示,CD147可能通過刺激透明質(zhì)酸的分泌誘導(dǎo)CD4十T細(xì)胞的活化,CD147能促進(jìn)單核細(xì)胞成熟及巨噬細(xì)胞分泌細(xì)胞因子,加強(qiáng)炎癥組織中單核/巨噬細(xì)胞的浸潤(rùn)。CD44是細(xì)胞表面的整合膜蛋白,屬粘附分子家族,它具有廣泛的生物學(xué)功能。研究表明CD44S與其它分子配合提供淋巴細(xì)胞激活的共刺激信號(hào),尤其是T淋巴細(xì)胞及NK等的激活。在激活過程中,CD44扮演“共刺激分子”的角色胞膜上的CD44分子與其配體透明質(zhì)酸或相應(yīng)抗體(抗CD44單抗)結(jié)合,作為共刺激分子同TCR/CD3復(fù)合體接受的刺激一起引起外周血T細(xì)胞的增殖,使Th細(xì)胞釋放IL-2,CTL細(xì)胞釋放胰蛋白醋酶。 為了解銀屑病中CD147、CD44的表達(dá)以及血中透明質(zhì)酸的變化,我們利用免疫組化的方法檢測(cè)了CD147、CD44在銀屑病患者及不同病期皮損中的表達(dá),并用放射免疫法測(cè)定血中透明質(zhì)酸的含量,從而探討它們?cè)阢y屑病中的作用。 方法:皮損標(biāo)本來源于2006年10月—2009年10月河北醫(yī)科大學(xué)第四醫(yī)院皮膚科門診就診患者,根據(jù)臨床表現(xiàn),初診為銀屑病患者,于局麻下在皮損部用環(huán)鉆取材,立即放入10%甲醛溶液中,石蠟包埋后備用。選取經(jīng)臨床結(jié)合組織病理確診為銀屑病患者標(biāo)本32例,其中男18例,女14例;年齡10-80歲,平均27.2歲。所有患者排除患有其他系統(tǒng)性疾病,且近3個(gè)月內(nèi)未曾接受任何治療。對(duì)照組標(biāo)本取自河北醫(yī)科大學(xué)第四醫(yī)院外科20例外傷手術(shù)患者的健康皮膚,對(duì)照組患者未患其他疾病,且年齡、性別及取材部位與銀屑病患者相匹配。組織病理采用石蠟切片HE染色觀察,免疫組化采用SP法,染色結(jié)果陽性著色為棕黃色顆粒。 應(yīng)用SPSS13.0統(tǒng)計(jì)軟件分析試驗(yàn)結(jié)果。免疫組化結(jié)果采用秩和檢驗(yàn)Mann-Whitney U檢驗(yàn)分析各項(xiàng)指標(biāo)在PS組和對(duì)照組表達(dá)情況,CD147與CD44的相關(guān)性采用Spearman等級(jí)相關(guān)分析。 結(jié)果: 1 CD147在正常皮膚角質(zhì)形成細(xì)胞中和銀屑病各組皮損角質(zhì)形成細(xì)胞、T細(xì)胞和中性粒細(xì)胞中均有表達(dá)。在32例銀屑病中,陽性表達(dá)共26例,其中強(qiáng)陽性8例,陽性、弱陽性各9例,陰性6例。正常對(duì)照組中,陰性18例,弱陽性1例,陽性1例,無強(qiáng)陽性表達(dá)。結(jié)果顯示,CD147在銀屑病中陽性表達(dá)均比正常對(duì)照組增高,差異有顯著性(P0.05),且在銀屑病的進(jìn)展期表達(dá)高于靜止期,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在不同性別、年齡及病程之間均無顯著性差別(P0.05。 2 CD44S在正常人皮膚、尋常型銀屑病皮損處及其相鄰?fù)庥^正常皮中均有表達(dá),其中在表皮細(xì)胞的棘細(xì)胞和基底細(xì)胞表面有表達(dá),顆粒層細(xì)胞及角質(zhì)層細(xì)胞均無表達(dá),在棘細(xì)胞表面的表達(dá)最強(qiáng)。真皮組織細(xì)胞中CD44S呈均一的表達(dá)。在皮膚附屬器中的毛囊,小汗腺及血管內(nèi)皮細(xì)胞上均有表達(dá)。在32例銀屑病患者中,陽性表達(dá)24例,其中強(qiáng)陽性5例,陽性9例,弱陽性10例,陰性8例。而對(duì)照組20例中僅1例陽性表達(dá),2例弱陽性表達(dá),其余為陰性表達(dá)。結(jié)果顯示,CD44在銀屑病中陽性表達(dá)均比正常對(duì)照組增高,差異有顯著性(P0.05),且在銀屑病的進(jìn)展期表達(dá)高于靜止期,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在不同性別、年齡及病程之間均無顯著性差別(P0.05)。 3我們以表皮層CD147明確表達(dá)陽性的26例標(biāo)本為陽性組,與另一組6例CD147明確表達(dá)陰性的標(biāo)本為對(duì)照組。CD147陽性組的血中透明質(zhì)酸水平高于對(duì)照組。 4 CD147與CD44在銀屑病患者同一皮損中的表達(dá)相關(guān)系數(shù)r=0.474,差異有顯著性,兩者呈正相關(guān)。 結(jié)論:根據(jù)實(shí)驗(yàn)結(jié)果得出以下結(jié)論: 1 CD147在銀屑病主要表達(dá)于角質(zhì)形成細(xì)胞、T細(xì)胞和中性粒細(xì)胞,并明顯高于對(duì)照組,且進(jìn)展期皮損高于靜止期。提示銀屑病皮損中CD147表達(dá)水平增高且與疾病分型和進(jìn)展程度關(guān)聯(lián)。 2 CD44S在尋常型銀屑病表達(dá)主要位于表皮細(xì)胞的棘細(xì)胞和基底細(xì)胞,在棘細(xì)胞表面的表達(dá)最強(qiáng);真皮組織細(xì)胞中CD44S呈均一的表達(dá);在皮膚附屬器中的毛囊,小汗腺及血管內(nèi)皮細(xì)胞上均有表達(dá)。并明顯高于對(duì)照組,且進(jìn)展期皮損高于靜止期。提示銀屑病皮損中CD44S表達(dá)水平增高且與疾病分型和進(jìn)展程度關(guān)聯(lián)。 3 CD147與CD44呈正相關(guān),提示透明質(zhì)酸在銀屑病中的作用,CD147分泌透明質(zhì)酸,與其受體CD44S相結(jié)合,作為共刺激分子同TCR/CD3復(fù)合體接受的刺激一起引起外周血T細(xì)胞的增殖。 4銀屑病中CD147陽性組的透明質(zhì)酸值明顯高于CD147陰性組,CD147的表達(dá)與透明質(zhì)酸呈正相關(guān),提示CD147的表達(dá)與透明質(zhì)酸生成有關(guān)。 5 CD147、CD44S與性別、年齡和病程之間均無相關(guān)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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R758.63

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