發(fā)布時(shí)間：2018-05-05 06:29

  本文選題：硬皮病 + UVA_1��； 參考：《第三軍醫(yī)大學(xué)》2008年碩士論文

【摘要】： 一、研究背景和目的 硬皮病是一種病因不明、發(fā)病機(jī)制尚不明確、主要以皮膚或內(nèi)臟器官纖維化、血管異常病變和免疫異常激活為主要特點(diǎn)的自身免疫性結(jié)締組織病。其中纖維化是硬皮病發(fā)病過(guò)程中最突出的特點(diǎn),也是嚴(yán)重影響病人生活質(zhì)量、甚至危及病人生命的主要威脅。研究表明:UVA能夠穿透表皮、真皮,甚至深達(dá)皮下,對(duì)局部照射部位的組織、細(xì)胞、血管以及DNA等產(chǎn)生影響,從而起到調(diào)節(jié)機(jī)體狀態(tài)和治療疾病的作用。已經(jīng)證實(shí)UVA具有抗炎、免疫調(diào)節(jié)及改善局部微循環(huán)等作用,在皮膚科其他疾病的治療上已經(jīng)應(yīng)用多年。近幾年,多個(gè)研究已經(jīng)表明應(yīng)用UVA1治療硬皮病患者取得了肯定療效,但對(duì)UVA1治療硬皮病的作用機(jī)制研究關(guān)注較少。 本研究首次在建立博萊霉素硬皮病小鼠模型的基礎(chǔ)上,觀察UVA1照射前后硬皮病小鼠局部注射部位皮膚的外觀變化、病理變化、羥脯氨酸含量及膠原含量變化,并測(cè)定TGFβ1、TGFβ2和decorin等與硬皮病發(fā)病機(jī)制密切相關(guān)的細(xì)胞因子的變化,試圖探索UVA1治療硬皮病的可能機(jī)制,為進(jìn)一步理解硬皮病的發(fā)病機(jī)制和探索新的治療手段提供重要的參考依據(jù)。 二、方法 用300μg/ml的博萊霉素每日注射BALB/c小鼠背部皮膚,連續(xù)28天,進(jìn)行模型構(gòu)建;之后,通過(guò)觀察注射部位皮膚外觀變化、皮損及肺部組織的組織病理變化、羥脯氨酸含量及膠原含量變化來(lái)驗(yàn)證模型構(gòu)建是否成功。用波長(zhǎng)365nm UVA1照射博來(lái)霉素誘導(dǎo)的硬皮病小鼠模型,觀察照射前后局部皮膚變化,組織病理變化、羥脯氨酸含量及膠原含量變化,并用免疫組化法及RT-PCR測(cè)定decorin、TGFβ1及TGFβ2等因子在各組小鼠皮膚的變化。 三、結(jié)果 1.從皮膚外觀變化、皮損及肺部組織的組織病理表現(xiàn)、羥脯氨酸含量及膠原含量驗(yàn)證了硬皮病小鼠模型構(gòu)建是成功的。 2. UVA1照射前后,照射組小鼠與模型組小鼠相比,局部硬化皮膚明顯軟化,與皮下粘連明顯減輕;羥脯氨酸含量及膠原含量顯著降低(P0.05);病理示:真皮層變薄,膠原纖維排列疏松,數(shù)量減少;從局部皮膚的外觀變化、皮膚組織病理和羥脯氨酸含量與膠原含量的變化三個(gè)方面均顯示出:UVA1照射可以有效改善硬皮病小鼠的硬化皮膚。 3.通過(guò)測(cè)定UVA1照射前后TGFβ1、TGFβ2和decorin的變化,顯示出:在UVA1照射前的硬皮病小鼠皮損內(nèi),TGFβ1、TGFβ2呈陽(yáng)性高表達(dá),decorin則呈現(xiàn)低表達(dá);在UVA1照射后的硬皮病小鼠皮損內(nèi),TGFβ1、TGFβ2呈較顯著的下調(diào)表達(dá),decorin則呈上調(diào)表達(dá)。 四、結(jié)論 1.不僅從外觀上,而且從組織病理、羥脯氨酸含量和膠原含量上均顯示出:UVA1光療可顯著改善硬皮病小鼠的硬化皮膚,使其明顯軟化,彈性恢復(fù),并使其羥脯氨酸含量和膠原含量有意義的下降,膠原纖維數(shù)目減少,排列疏松。 2.通過(guò)觀察UVA1照射前后TGFβ1、TGFβ2和decorin的變化,推測(cè)UVA1對(duì)硬皮病小鼠模型影響的機(jī)制可能與UVA1照射后下調(diào)TGFβ1、TGFβ2和上調(diào)decorin有關(guān)。
[Abstract]:First, research background and purpose
Scleroderma is a kind of autoimmune connective tissue disease which is mainly characterized by fibrosis of the skin or viscera, abnormal vascular lesions and activation of immune abnormality, among which fibrosis is the most prominent characteristic of scleroderma, and it is also a serious influence on the quality of life of the patients and even endanger the disease. The main threat of human life. Studies have shown that UVA can penetrate the epidermis, dermis, even deep to the subcutaneous, and affect the tissues, cells, blood vessels and DNA of the local irradiated parts, which can regulate the state of the body and treat the disease. It has been proved that UVA has the effect of anti-inflammatory, immunoregulation and improvement of local microcirculation, in the Department of dermatology. The treatment of his disease has been used for many years. In recent years, many studies have shown that the application of UVA1 in the treatment of scleroderma has achieved positive results, but there is less attention in the study of the mechanism of UVA1 for scleroderma.
On the basis of the establishment of a mouse model of bleomycin scleroderma for the first time, the changes in the skin appearance, pathological changes, the changes of hydroxyproline content and the content of collagen in the local injection site of scleroderma before and after UVA1 irradiation were observed, and the changes of cytokines, such as TGF beta 1, TGF beta 2 and decorin, were measured, and the changes in the cell factors closely related to the pathogenesis of scleroderma were measured. The purpose of this study is to explore the possible mechanism of UVA1 in the treatment of scleroderma so as to provide an important reference for further understanding the pathogenesis of scleroderma and exploring new therapeutic methods.
Two, method
300 g/ml of bleomycin was injected into the back skin of BALB/c mice daily for 28 days and the model was constructed. After that, the skin appearance changes, skin lesions and pathological changes of the lung tissue were observed, the content of hydroxyproline and the content of collagen were observed to verify the success of the model construction. The wavelength of 365nm UVA1 was used to irradiate bleomycin. In the induced scleroderma mouse model, the changes of local skin and histopathology, the content of hydroxyproline and the content of collagen were observed before and after irradiation, and the changes of decorin, TGF beta 1 and TGF beta 2 were measured by immunohistochemistry and RT-PCR.
Three, the result
1. from the changes of skin appearance, histopathological findings of skin and lung tissue, hydroxyproline content and collagen content, it is proved that the construction of scleroderma mouse model is successful.
2. UVA1 irradiation, compared with the model group, the mice in the irradiated group were obviously softened and decreased with the subcutaneous adhesion, the content of hydroxyproline and the content of collagen decreased significantly (P0.05), and the pathology showed that the dermis became thinner, the collagen fibers were loosely arranged and the quantity decreased; the appearance of the skin, the histopathology of the skin and the hydroxyproline from the local skin. Three aspects of acid content and collagen content change showed that UVA1 irradiation could effectively improve scleroderma in scleroderma mice.
3. by measuring the changes of TGF beta 1, TGF beta 2 and decorin before and after UVA1 irradiation, it showed that in the skin lesions of scleroderma mice before UVA1 irradiation, TGF beta 1, TGF beta 2 showed positive high expression, decorin showed low expression, and TGF beta 1 and TGF beta 2 were significantly downregulated in the skin lesions of scleroderma after UVA1 irradiation, and the decorin was up expression.
Four. Conclusion
1. not only the appearance, but also the histopathology, the content of hydroxyproline and the content of collagen showed that UVA1 phototherapy could significantly improve the hardened skin of scleroderma mice, make it soften obviously, restore the elasticity, decrease the content of hydroxyproline and collagen, decrease the number of collagen fibers, and arrange the arrangement loosely.
2. by observing the changes of TGF beta 1, TGF beta 2 and decorin before and after UVA1 irradiation, it is presumed that the mechanism of UVA1 on scleroderma mouse model may be related to the downregulation of TGF beta 1, TGF beta 2 and up regulation of decorin after UVA1 irradiation.

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類(lèi)號(hào)】：R593.25;R-332

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 劉麗艷;食品中非法添加劑和生物樣品中神經(jīng)遞質(zhì)含量檢測(cè)方法的研究[D];河北大學(xué);2011年

，

本文編號(hào)：1846631