Bcl-w和Beclin1在外阴上皮内非瘤样病变中的表达及意义

发布时间：2018-05-10 11:30

本文选题：外阴上皮内非瘤样病变 + 凋亡　；参考：《泸州医学院》2014年硕士论文

【摘要】：目的：通过免疫组化法检测凋亡相关蛋白Bcl-w及Beclin1在外阴上皮内非瘤样病变(nonneoplastic epithelial disorders of vulvar, NNEDV)皮肤组织中的表达并分析二者相关性，探讨细胞凋亡是否参与NNEDV发病过程，以及凋亡相关蛋白Bcl-w及Beclin1在NNEDV发病中可能存在的作用机制，为NNEDV的临床诊治及进一步研究提供实验依据。方法：收集因外阴瘙痒行外阴病变部位皮肤活检术患者的外阴病变部位（病变组）皮肤组织标本，常规石蜡包埋后切片诊断，筛选出其中经病理联合临床综合确诊为外阴上皮内非瘤样病变的皮肤标本共42例，其中鳞状上皮增生型（VSH）20例，硬化苔藓型（VLS）15例，混合型7例；同时，收集患者外阴靠近肉眼色素缺失部位的肉眼观正常的病变旁（病变旁组）皮肤组织标本。采用原位末端标记（TdT-mediated dUTP Nick-End Labeling, Tunel）细胞凋亡检测试剂盒检测各组皮肤上皮细胞凋亡情况。采用免疫组化法检测凋亡相关蛋白Bcl-w及Beclin1在各组外阴皮肤上皮细胞中的表达，，应用Image Pro6.0专业图像分析系统分析阳性细胞平均光密度（mean optical density, MOD）值，分析二者在各组外阴皮肤上皮细胞中的表达差异及相关性。采用SPSS20.0统计软件包处理实验数据，P0.05差异有统计学意义。结果：1、上皮细胞凋亡指数（apoptosis index, AI），在VSH与VLS型患者中，病变组均明显小于病变旁组（P0.05）；在混合型患者中，病变组略小于病变旁组（P0.05）。2、Bcl-w的表达，在VSH型患者中，病变组明显高于病变旁组（P0.05）；在VLS型及混合型患者中，病变组与病变旁组间Bcl-w的表达无统计学差异（P0.05）。3、Beclin1的表达，在VSH型患者中，病变组明显低于病变旁组（P0.05）；在VLS型及混合型患者中，病变组与病变旁组间Beclin1的表达无统计学差异（P0.05）。4、相关性：Bcl-w与Beclin1的表达，在VSH型患者病变组（r=0.017, P=0.9440.05）、病变旁组（r=0.101,P=0.6710.05）皮肤组织中均呈不相关；在VLS型患者病变组呈正相关(r=0.527, P=0.0430.05)，病变旁组呈不相关（r=0.472, P=0.0760.05）；在混合型患者病变组（r=-0.070, P=0.8820.05）、病变旁组（r=-0.084,P=0.8590.05）皮肤组织中均呈不相关。结论：1、NNEDV三种病理类型患者外阴鳞状上皮细胞的凋亡指数AI病变组均小于病变旁组，表明细胞凋亡异常可能是参与NNEDV发生发展的重要因素之一；同时，病变组与病变旁组的凋亡指数相比，在外阴上皮内非瘤样病变VSH型及VLS型患者中差异明显，而在混合型患者中差异不明显，提示凋亡异常在NNEDV不同病理类型的形成过程中发挥的作用可能存在差异。2、Bcl-w仅在VSH型患者的病变组与病变旁组间的表达差异明显，且病变组明显高于病变旁组，表明Bcl-w参与的抗凋亡作用可能也仅在VSH型病理类型的形成过程中起重要作用，抗凋亡作用明显增强，使得病变部位外阴上皮细胞凋亡减少，增殖能力增强，使得外阴鳞状上皮增生明显，参与VSH病理类型的形成。3、Beclin1仅在VSH型患者的病变组与病变旁组间的表达差异明显，且在病变组中的表达低于病变旁组，由此推测三种病理类型中Beclin1所介导的细胞自噬性凋亡作用明显减弱可能仅存在于VSH型病理类型的形成过程中，从而直接或间接地引起外阴病变部位细胞凋亡能力减弱，增殖能力相对增强，从而促使外阴上皮内非瘤样病变VSH型病理类型的发展形成；而VLS型及混合型病理类型形成过程中可能不存在Beclin1的细胞自噬性凋亡作用减弱或减弱作用不明显，在这两种病理类型的形成中，Beclin1可能不起重要作用。4、NNEDV三种病理类型中，Bcl-w与Beclin1仅在VLS型患者的病变组呈正相关，表明Bcl-w与Beclin1可能仅在VLS型病理类型的形成过程中可能存在相互协同或促进关系。
[Abstract]:Objective: to detect the expression of apoptosis related protein Bcl-w and Beclin1 in the skin tissues of Nonneoplastic Epithelial Disorders of vulvar, NNEDV by immunohistochemistry and analyze the correlation between the two groups and to explore whether apoptosis participates in the pathogenesis of NNEDV, and the apoptosis related proteins Bcl-w and Beclin1 are in NNEDV. The possible mechanism of action may provide experimental basis for the clinical diagnosis and treatment and further research of NNEDV. Methods: to collect the skin tissue specimens of the vulvar lesions (pathological group) of the patients with vulvar itching in the skin biopsy of the vulvar lesions. A total of 42 skin specimens were diagnosed as non neoplastic lesions of the vulvar epithelium, including 20 cases of squamous epithelial hyperplasia (VSH), 15 cases of lichen Sclerotinia (VLS) and 7 cases of mixed type. At the same time, the skin tissue specimens were collected from the naked eye adjacent to the naked eye, which was near the naked eye pigments. In situ end labeling (TdT-mediated dUT) was used. P Nick-End Labeling, Tunel) cell apoptosis detection kit was used to detect the apoptosis of skin epithelial cells in each group. Immunohistochemical method was used to detect the expression of apoptosis related protein Bcl-w and Beclin1 in the skin epithelial cells of each group, and the Image Pro6.0 professional image analysis system was used to analyze the average optical density of the positive cells (mean optical density). MOD) value, analysis of the expression difference and correlation between the two groups in the vulva skin epithelial cells. The SPSS20.0 statistical package was used to deal with the experimental data. The difference of P0.05 was statistically significant. Results: 1, the epithelial cell apoptosis index (apoptosis index, AI), in the patients with VSH and VLS, the lesion groups were significantly smaller than those in the para pathological group (P0.05); The lesion group was slightly less than the parababal group (P0.05).2, Bcl-w expression, and in VSH patients, the lesion group was significantly higher than that of the parababal group (P0.05). In VLS and mixed patients, the expression of Bcl-w between the lesion group and the parabed group was not statistically different (P0.05).3, the expression of Beclin1, in VSH type patients, was significantly lower than that of the lesion group. Group (P0.05); in patients with type VLS and mixed type, the expression of Beclin1 between the lesion group and the adjacent group had no statistical difference (P0.05).4, correlation: the expression of Bcl-w and Beclin1, in the pathological group of VSH patients (r=0.017, P=0.9440.05), and in the skin tissue of the side group (r=0.101, P=) in the lesion group, Cheng Zhengxiang R=0.527 (P=0.0430.05), the parathal group was unrelated (r=0.472, P=0.0760.05); in the mixed patients (r=-0.070, P=0.8820.05), and in the parathal group (r=-0.084, P=0.8590.05), the skin tissues were not related. Conclusion: 1, the apoptotic index AI lesions in the squamous epithelial cells of the three types of NNEDV are less than those in the lesion group. Group, indicating that abnormal apoptosis may be one of the important factors involved in the development of NNEDV. At the same time, compared with the apoptotic index in the paratunal group, the pathological group is significantly different in the VSH type and VLS type of the non tumor like lesions in the vulvar epithelium, but the difference is not obvious in the mixed type patients, suggesting that the abnormal apoptosis is in the form of different pathological types of NNEDV. There may be differences in the role of.2 in the process of formation, and the difference in expression of Bcl-w only between the patients with VSH type and the parathal group is obvious, and the lesion group is obviously higher than that in the parathal group. It shows that the anti apoptosis effect of Bcl-w may also play an important role in the formation of VSH type, and the anti apoptosis effect is obviously enhanced and the disease is diseased. The apoptosis of the vulvar epithelial cells in the variant part of the vulvar cells was reduced and the proliferation ability was enhanced. The hyperplasia of the squamous epithelium of the vulva was obvious, and it was involved in the formation of.3 in the pathological type of VSH. The expression of Beclin1 was significantly different between the lesion group and the paracathal group of the VSH type, and the expression in the lesion group was lower than that in the parathula group. Therefore, it was suggested that the three pathological types were mediated by Beclin1. The obvious weakening of autophagic apoptosis in the cells may only exist in the formation of VSH type pathological types, which directly or indirectly causes the apoptotic capacity of the cells in the vulvar lesion to be weakened, and the proliferation ability is relatively enhanced, thus promoting the development of the type of VSH type disease in the inner non tumor like lesions of the vulvar epithelium; and VLS and mixed types. The role of Beclin1's autophagic apoptosis may not be weakened or weakened during the formation of pathological types. In the formation of these two types of Pathology, Beclin1 may not play an important role in.4, and in the three pathological types of NNEDV, Bcl-w and Beclin1 are only positively correlated with the group of VLS patients, suggesting that Bcl-w and Beclin1 may be only in the case of Beclin1. There may be synergistic or facilitating relationships in the development of type VLS pathology.

【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33

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