FGF10单克隆抗体对豚鼠银屑病样模型中VEGF、PCNA表达影响

发布时间：2018-05-15 11:35

本文选题：银屑病 + FGF-10单克隆抗体　；参考：《吉林大学》2013年硕士论文

【摘要】：银屑病是一种发生在一定的遗传背景下,多种环境与免疫因素共同参与所致的慢性炎症性增生性皮肤病，具有病程长、易反复、难根治的特点，为患者带来巨大的生理损害及心理压力。银屑病的发病机制十分复杂，其中免疫学发病机制占重要地位。目前认为T淋巴细胞活化是其中的枢纽环节：活化的T淋巴细胞介导一系列细胞因子如IL-2、IL-6、IL-8、IL-17、TNF-α、IFN-γ等的表达升高，刺激角质形成细胞增生，诱导血管内皮细胞和角质形成细胞表达血管内皮生长因子（VEGF）、ICAM-1、VCAM-1等，引起新生血管生成及白细胞粘附、外渗，使银屑病在组织病理学上表现为角化不全，表皮棘层增生肥厚，真皮内毛细血管扩张增生，血管周围炎症细胞浸润等。由间质细胞分泌的成纤维细胞生长因子-10（FGF-10）能特异性地刺激表皮细胞生长，在维持其表皮细胞异常增殖状态中起重要作用。本实验基于以上理论，利用免疫组织化学方法检测经FGF-10单克隆抗体治疗前后的豚鼠银屑病样模型中血管内皮生长因子（VEGF）和衡量细胞增殖程度的指标之一增殖细胞核抗原（PCNA）的表达情况，探讨FGF-10单克隆抗体对于银屑病皮损的影响及作用机制，为FGF-10单克隆抗体治疗银屑病这一新的生物治疗方法奠定理论基础。目的： 1.比较经FGF-10单克隆抗体治疗前后的豚鼠银屑病样模型中VEGF、PCNA表达的差异。 2.初步探讨FGF-10单克隆抗体对豚鼠银屑病样模型的部分作用机制,为FGF-10单克隆抗体治疗银屑病提供理论依据。方法：采用链霉菌抗生物素蛋白-过氧化物酶连接法（S-P法）对108例豚鼠耳部石蜡包埋组织标本（包括空白组、模型组、FGF-10单克隆抗体高、中、低剂量治疗组、丁酸氢化可的松治疗组）进行免疫组化染色，分别检测其中VEGF、PCNA的表达水平，采用半定量计分法评分，观察记录各组间2种细胞因子表达程度的强弱，利用SPSS13.0进行统计分析，判定各组间VEGF、PCNA表达水平的差异。结果： 1. VEGF在空白组、丁酸氢化可的松治疗组及FGF-10单克隆抗体治疗组的表达均低于模型组，结果均具有统计学意义（P0.05）；在FGF-10单克隆抗体高剂量治疗组和中剂量治疗组的表达低于丁酸氢化可的松治疗组及FGF-10单克隆抗体低剂量治疗组，结果均具有统计学意义（P0.05）；FGF-10单克隆抗体高剂量治疗组和中剂量治疗组相比较、丁酸氢化可的松治疗组及FGF-10单克隆抗体低剂量治疗组相比较均无统计学意义（P0.05）。 2.PCNA在空白组、丁酸氢化可的松组及FGF-10单克隆抗体治疗组的表达均低于模型组，结果均具有统计学意义（P0.05）；在FGF-10单克隆抗体治疗组组间比较显示：PCNA在剂量较高治疗组的表达低于剂量较低治疗组，结果均有统计学意义（P0.05）；FGF-10单克隆抗体高剂量治疗组与空白组相比较、FGF10单克隆抗体中剂量治疗组与丁酸氢化可的松治疗组相比较均无统计学意义（P0.05）。结论： 1.VEGF与PCNA在豚鼠银屑病样模型组的表达明显升高，提示二者可能参与银屑病的发病过程。 2.FGF-10单克隆抗体可降低豚鼠耳部银屑病样模型中PCNA、 VEGF的表达水平,由此推测FGF10单克隆抗体可能通过抑制银屑病表皮细胞异常增殖及真皮内新生血管的形成而对银屑病皮损产生一定的治疗作用。 3. FGF-10单克隆抗体各剂量治疗组之间两两比较：在高剂量治疗组中PCNA表达的被抑制程度强于其他两组，，但VGEF表达的被抑制程度与中剂量治疗组相比无差异，因此判定FGF-10单克隆抗体最佳治疗浓度尚需进一步观察及全面综合衡量。
[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 - 伪 , IFN - 纬 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 .

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R758.63

【参考文献】