HMGB1蛋白在扁平苔藓发病机制中的作用

发布时间：2018-01-05 06:38

本文关键词：HMGB1蛋白在扁平苔藓发病机制中的作用　出处：《吉林大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:扁平苔藓是一种病因尚未明确的慢性炎症性皮肤病,细胞免疫在其发病中起重要作用。细胞外的HMGB1蛋白作为损伤相关模式分子的代表,在多种炎症和自身免疫性疾病的发病机制中发挥重要作用,但其在扁平苔藓发病机制中的作用未见报道。目的:观察扁平苔藓及正常人皮肤组织HMGB1蛋白的表达情况进行检测,探讨HMGB1蛋白在扁平苔藓发病机制中的作用方法:免疫组化检测扁平苔藓及正常人皮肤组织中HMGB1蛋白表达及分布情况,比较不同类型扁平苔藓HMGB1的表达分布,比较初期、成熟期及消退期扁平苔藓HMGB1的表达分布,比较扁平苔藓皮损内、皮损边缘及皮损外正常皮肤皮肤的表达分布,并分析HMGB1在表皮角质形成细胞核内的阳性率与真皮炎性细胞浸润程度的相关性。结果:1.HMGB1蛋白在扁平苔藓表皮细胞胞核的阳性细胞比例较正常皮肤降低,细胞浆、细胞外间隙阳性分布较正常皮肤显著升高(P0.05),阳性细胞以表皮基底层和棘层中下部为主。2.HMGB1蛋白在扁平苔藓不同亚型(急性泛发性扁平苔藓,慢性局限性扁平苔藓、口唇扁平苔藓、肥厚性扁平苔藓、毛囊性扁平苔藓、反向性扁平苔藓、色素性扁平苔藓、萎缩性扁平苔藓)都具有上述扁平苔藓的共同特点。但也有差异:急性泛发性扁平苔藓表皮较角质形成细胞核阳性率较其他亚型高;色素性扁平苔藓、萎缩性扁平苔藓胞浆及细胞外间隙分布较其他亚型低。3.HMGB1在不同时期扁平苔藓的分布:HMGB1蛋白在不同时期扁平苔藓皮损表皮细胞的表达分布各有差异。初期、成熟期扁平苔藓皮损表皮细胞核阳性率较消退期扁平苔藓低,但初期扁平苔藓皮损表皮细胞浆及细胞外间隙阳性率较成熟期扁平苔藓和消退期扁平苔藓高,且成熟期扁平苔藓表皮细胞浆及细胞外间隙阳性率较消退期扁平苔藓高。以上差异均有统计学意义(P0.05)。4.HMGB1蛋白在扁平苔藓皮损不同部位细胞核、细胞浆及细胞外间质的表达百分比,细胞核:皮损内皮损边缘皮损外正常皮肤;细胞浆:皮损边缘较皮损外正常皮肤和皮损内增高;细胞外间隙:皮损边缘较皮损外正常皮肤和皮损内增高。所有差异都具显著性(P0.05)。5.HMGB1在表皮角质形成细胞核的阳性率与真皮炎性细胞浸润数呈负相关,(y=-25.58X+1507 R=-0.853,p0.001),即表皮内细胞细胞核阳性率越低,真皮内炎性细胞浸润数越多。结论:1.与正常皮肤相比,扁平苔藓皮损中HMGB1核表达降低,胞浆、细胞外间隙表达升高,且在扁平苔藓发病初期和皮损边缘更显著,提示HMGB1由胞核向胞浆、细胞外间隙的转移可能与扁平苔藓炎症发生有关;2.HMGB1在扁平苔藓表皮角质形成细胞核阳性率与真皮淋巴细胞浸润数呈负相关,进一步提示HMGB1由胞核向胞浆、细胞外间隙的转移由与扁平苔藓真皮淋巴细胞浸润相关。
[Abstract]:Background: lichen planus is a chronic inflammatory skin disease with unknown etiology. Cellular immunity plays an important role in the pathogenesis of lichen planus. Extracellular HMGB1 protein is the representative of damage related model molecules. It plays an important role in the pathogenesis of many kinds of inflammation and autoimmune diseases. But its role in the pathogenesis of lichen planus has not been reported. Objective: to observe the expression of HMGB1 protein in lichen planus and normal human skin. To investigate the role of HMGB1 protein in the pathogenesis of lichen planus methods: immunohistochemistry was used to detect the expression and distribution of HMGB1 protein in lichen planus and normal human skin. To compare the expression distribution of HMGB1 in different types of lichen planus, the expression distribution of HMGB1 in early stage, mature stage and extinction stage, and compare the expression distribution of HMGB1 in the lesions of lichen planus. The distribution of the expression of normal skin on the edge of the lesion and the skin outside the lesion. The relationship between the positive rate of HMGB1 in keratinocytes and the degree of dermal inflammatory cell infiltration was analyzed. 1. The proportion of HMGB1 protein positive cells in the nucleus of lichen planus epidermis cells was lower than that in normal skin. The positive distribution of cytoplasm and extracellular space was significantly higher than that of normal skin (P0.05). The positive cells were mainly epidermal basal layer and middle and lower part of spinous layer. 2. HMGB1 protein was found in different subtypes of lichen planus (acute generalized lichen planus, chronic localized lichen planus, oral lichen planus). Hypertrophic lichen planus, follicular lichen planus, reverse lichen planus, and pigmented lichen planus. Atrophic lichen planus) all have the same characteristics of the above lichen planus, but there are also differences: the positive rate of keratinocyte in acute generalized lichen planus is higher than that in other subtypes. Luteous lichen planus. The distribution of cytoplasm and extracellular space in atrophic lichen planus was lower than that in other subtypes. 3. The distribution of HMGB1 in different stages of lichen planus:. The expression and distribution of HMGB1 protein in epidermal cells of lichen planus were different at different stages. The positive rate of epidermal nuclei in mature lichen planus was lower than that in dissipated lichen planus, but the positive rate of epidermal cytoplasm and extracellular space in primary lichen planus was higher than that in mature lichen planus and extinction lichen planus. The positive rates of epidermal cytoplasm and extracellular space in mature lichen planus were higher than those in dissipated lichen planus. 4. HMGB1 protein was located in the nuclei of different parts of lichen planus lesions. Percentage of expression of cytoplasm and extracellular stroma, nucleus: normal skin outside the edge of skin lesion; Cytoplasm: the edge of the lesions was higher than that of the normal skin and the lesions. Extracellular space: the edge of the lesions was higher than that of the normal skin and the lesions. All the differences were significant (P0.05). The positive rate of HMGB1 in keratinocytes was negatively correlated with the number of dermal inflammatory cells. The positive rate of cell nucleus in epidermis was lower than that in the epidermis. Conclusion 1. Compared with normal skin, the expression of HMGB1 in the lesions of lichen planus decreased, and the expression of cytoplasm and extracellular space increased. Moreover, it was more obvious in the early stage of lichen planus and the edge of lesions, suggesting that the transfer of HMGB1 from nucleus to cytoplasm and the transfer of extracellular space may be related to the occurrence of lichen planus inflammation. 2. The positive rate of HMGB1 in epidermal keratinocytes of lichen planus was negatively correlated with the number of dermal lymphocyte infiltration, which further suggested that HMGB1 changed from nucleus to cytoplasm. Metastasis of the extracellular space is associated with lymphocytic infiltration in the dermis of lichen planus.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.65

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