發(fā)布時(shí)間：2018-05-15 11:35

  本文選題：銀屑病 + FGF-10單克隆抗體�。� 參考：《吉林大學(xué)》2013年碩士論文

【摘要】：銀屑病是一種發(fā)生在一定的遺傳背景下,多種環(huán)境與免疫因素共同參與所致的慢性炎癥性增生性皮膚病，具有病程長(zhǎng)、易反復(fù)、難根治的特點(diǎn)，為患者帶來(lái)巨大的生理?yè)p害及心理壓力。 銀屑病的發(fā)病機(jī)制十分復(fù)雜，其中免疫學(xué)發(fā)病機(jī)制占重要地位。目前認(rèn)為T(mén)淋巴細(xì)胞活化是其中的樞紐環(huán)節(jié)：活化的T淋巴細(xì)胞介導(dǎo)一系列細(xì)胞因子如IL-2、IL-6、IL-8、IL-17、TNF-α、IFN-γ等的表達(dá)升高，刺激角質(zhì)形成細(xì)胞增生，誘導(dǎo)血管內(nèi)皮細(xì)胞和角質(zhì)形成細(xì)胞表達(dá)血管內(nèi)皮生長(zhǎng)因子（VEGF）、ICAM-1、VCAM-1等，引起新生血管生成及白細(xì)胞粘附、外滲，使銀屑病在組織病理學(xué)上表現(xiàn)為角化不全，表皮棘層增生肥厚，真皮內(nèi)毛細(xì)血管擴(kuò)張?jiān)錾�，血管周�(chē)装Y細(xì)胞浸潤(rùn)等。由間質(zhì)細(xì)胞分泌的成纖維細(xì)胞生長(zhǎng)因子-10（FGF-10）能特異性地刺激表皮細(xì)胞生長(zhǎng)，在維持其表皮細(xì)胞異常增殖狀態(tài)中起重要作用。 本實(shí)驗(yàn)基于以上理論，利用免疫組織化學(xué)方法檢測(cè)經(jīng)FGF-10單克隆抗體治療前后的豚鼠銀屑病樣模型中血管內(nèi)皮生長(zhǎng)因子（VEGF）和衡量細(xì)胞增殖程度的指標(biāo)之一增殖細(xì)胞核抗原（PCNA）的表達(dá)情況，探討FGF-10單克隆抗體對(duì)于銀屑病皮損的影響及作用機(jī)制，為FGF-10單克隆抗體治療銀屑病這一新的生物治療方法奠定理論基礎(chǔ)。 目的： 1.比較經(jīng)FGF-10單克隆抗體治療前后的豚鼠銀屑病樣模型中VEGF、PCNA表達(dá)的差異。 2.初步探討FGF-10單克隆抗體對(duì)豚鼠銀屑病樣模型的部分作用機(jī)制,為FGF-10單克隆抗體治療銀屑病提供理論依據(jù)。 方法： 采用鏈霉菌抗生物素蛋白-過(guò)氧化物酶連接法（S-P法）對(duì)108例豚鼠耳部石蠟包埋組織標(biāo)本（包括空白組、模型組、FGF-10單克隆抗體高、中、低劑量治療組、丁酸氫化可的松治療組）進(jìn)行免疫組化染色，分別檢測(cè)其中VEGF、PCNA的表達(dá)水平，采用半定量計(jì)分法評(píng)分，觀察記錄各組間2種細(xì)胞因子表達(dá)程度的強(qiáng)弱，利用SPSS13.0進(jìn)行統(tǒng)計(jì)分析，判定各組間VEGF、PCNA表達(dá)水平的差異。 結(jié)果： 1. VEGF在空白組、丁酸氫化可的松治療組及FGF-10單克隆抗體治療組的表達(dá)均低于模型組，結(jié)果均具有統(tǒng)計(jì)學(xué)意義（P0.05）；在FGF-10單克隆抗體高劑量治療組和中劑量治療組的表達(dá)低于丁酸氫化可的松治療組及FGF-10單克隆抗體低劑量治療組，結(jié)果均具有統(tǒng)計(jì)學(xué)意義（P0.05）；FGF-10單克隆抗體高劑量治療組和中劑量治療組相比較、丁酸氫化可的松治療組及FGF-10單克隆抗體低劑量治療組相比較均無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。 2.PCNA在空白組、丁酸氫化可的松組及FGF-10單克隆抗體治療組的表達(dá)均低于模型組，結(jié)果均具有統(tǒng)計(jì)學(xué)意義（P0.05）；在FGF-10單克隆抗體治療組組間比較顯示：PCNA在劑量較高治療組的表達(dá)低于劑量較低治療組，結(jié)果均有統(tǒng)計(jì)學(xué)意義（P0.05）；FGF-10單克隆抗體高劑量治療組與空白組相比較、FGF10單克隆抗體中劑量治療組與丁酸氫化可的松治療組相比較均無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。 結(jié)論： 1.VEGF與PCNA在豚鼠銀屑病樣模型組的表達(dá)明顯升高，提示二者可能參與銀屑病的發(fā)病過(guò)程。 2.FGF-10單克隆抗體可降低豚鼠耳部銀屑病樣模型中PCNA、 VEGF的表達(dá)水平,由此推測(cè)FGF10單克隆抗體可能通過(guò)抑制銀屑病表皮細(xì)胞異常增殖及真皮內(nèi)新生血管的形成而對(duì)銀屑病皮損產(chǎn)生一定的治療作用。 3. FGF-10單克隆抗體各劑量治療組之間兩兩比較：在高劑量治療組中PCNA表達(dá)的被抑制程度強(qiáng)于其他兩組，，但VGEF表達(dá)的被抑制程度與中劑量治療組相比無(wú)差異，因此判定FGF-10單克隆抗體最佳治療濃度尚需進(jìn)一步觀察及全面綜合衡量。
[Abstract]:The psoriasis is a kind of chronic inflammatory hyperplasia dermatosis which takes place in a certain genetic background , multiple environment and immune factors , and has the characteristics of long duration , easy and repeated , difficult radical treatment , and brings great physiological damage and psychological pressure for the patient .

The pathogenesis of psoriasis is very complex , in which immunological pathogenesis is important . It is believed that the activation of T lymphocytes is the pivotal link in the pathogenesis of psoriasis . The expression of cytokines such as IL - 2 , IL - 6 , IL - 8 , IL - 17 , TNF - 偽 , IFN - 緯 and so on is mediated by activated T - lymphocytes . The expression of vascular endothelial growth factor ( VEGF ) , ICAM - 1 , VCAM - 1 and so on are caused by activated T lymphocytes . The fibroblast growth factor - 10 ( FGF - 10 ) secreted by the stromal cells can specifically stimulate the growth of epidermal cells and play an important role in the maintenance of abnormal proliferation of epidermal cells .

Based on the above theory , the expression of vascular endothelial growth factor ( VEGF ) and proliferating cell nuclear antigen ( PCNA ) in guinea pig psoriasis - like model before and after treatment with monoclonal antibody of FGF - 10 were detected by immunohistochemical method , and the effect and mechanism of FGF - 10 monoclonal antibody on psoriasis lesions were investigated .

Purpose :

1 . To compare the expression of VEGF and PCNA in the psoriasis - like model of guinea pigs before and after treatment with the FGF - 10 monoclonal antibody .

2 . To investigate the partial mechanism of FGF - 10 monoclonal antibody against psoriasis - like model in guinea pig , and provide theoretical basis for the treatment of psoriasis with the monoclonal antibody of FGF - 10 .

Method :

The expression levels of VEGF and PCNA in 108 guinea pig ear wax - embedded tissues were detected by streptavidin - peroxidase ( S - P method ) . The expression level of VEGF and PCNA was detected by semi - quantitative scoring method .

Results :

1 . The expression of VEGF in blank group , hydrocortisone treatment group and FGF - 10 monoclonal antibody treatment group was lower than that in model group , and the results were statistically significant ( P0.05 ) .
The expression of FGF - 10 monoclonal antibody high - dose treatment group and medium - dose treatment group was lower than that of hydrocortisone butyrate treatment group and FGF - 10 monoclonal antibody low - dose treatment group , and the results were statistically significant ( P0.05 ) .
There was no statistical difference between the treatment group of hydrocortisone butyrate and the low dose of FGF - 10 monoclonal antibody ( P0.05 ) .

2 . The expressions of PCNA in blank group , hydrocortisone group and FGF - 10 monoclonal antibody treatment group were lower than those in model group ( P0.05 ) .
The expression of PCNA in the higher - dose group was lower than that in the lower - dose treatment group ( P0.05 ) .
Compared with blank group , FGF - 10 monoclonal antibody high - dose treatment group had no statistical significance compared with that of hydrocortisone butyrate ( P0.05 ) .

Conclusion :

1 . The expression of VEGF and PCNA in the psoriasis - like model group increased significantly , suggesting that both VEGF and PCNA might participate in the pathogenesis of psoriasis .

2 . The monoclonal antibody of FGF - 10 can reduce the expression level of PCNA and VEGF in the psoriasis - like model of guinea pig ears , and thus it is speculated that the monoclonal antibody of FGF10 may have a certain therapeutic effect on psoriasis lesions by inhibiting the abnormal proliferation of psoriasis epidermal cells and the formation of neovascularization in the dermis .

3 . Compared with the other two groups , the level of inhibition of PCNA expression in the high - dose treatment group was stronger than that in the other two groups , but the level of inhibition of the expression of the VGEF was not different from that in the medium - dose treatment group . Therefore , it was determined that the optimal therapeutic concentration of the FGF - 10 monoclonal antibody needed to be further observed and comprehensively measured .

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R758.63

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