【作者】 邓冠红；

【导师】 陈作良； 梁甲兴；

【作者基本信息】 福建医科大学 ， 口腔临床医学， 2007， 硕士

【摘要】 目的:通过探讨口腔扁平苔藓(oral lichen planus, OLP)中CD4+、CD8+T细胞及CD4/CD8比例的变化,了解细胞免疫在OLP发病中的作用;通过对细胞凋亡的研究,进一步了解细胞凋亡与OLP的发病关系;通过研究OLP中TGF-β1及Smad4、Smad7蛋白的表达和分布,分析OLP中细胞免疫与细胞凋亡的关系,进一步了解OLP发病机制。方法:采用免疫组化SP法检测27例OLP患者病变组织、10例正常口腔粘膜(normal oral mucosa, NOM)组织中CD4+T细胞、CD8+T细胞、TGF-β1及Smad4、Smad7蛋白的表达水平,并用脱氧核糖核甘酸末端转移酶介导的原位缺口末端标记法(TUNEL法)检测OLP中细胞凋亡指数(apoptotic index, AI),并对实验结果进行统计分析。结果:①OLP固有层中CD8+T细胞数为35.57±4.25,比正常对照组7.57±3.14显著增高(P<0.05); CD4+T细胞数为17.81±5.13,比正常对照组10.68±4.81显著增高(P<0.05);CD4/CD8为0.51±0.17与正常对照组1.54±0.78相比差异有统计学意义(P<0.05)。②OLP中上皮细胞的AI为14.26±2.32,比正常对照组6.69±0.64显著增加(P<0.05)。固有层淋巴细胞的AI为8.52±2.34,比正常对照组20.14±7.27显著减少(P<0.05)。③OLP中上皮细胞TGF-β1、Smad7及Smad4的平均染色强度分别为0.4839±0.2545、0.5852±0.2504、0.3681±0.1827,其中TGF-β1、Smad7与正常对照组相比表达增高,差异有统计学意义(P<0.05)。但糜烂型与非糜烂型OLP中TGF-β1、Smad7及Smad4的表达差异均无统计学意义(P>0.05)。④OLP固有层CD8+T细胞数与病程呈正相关(r=0.553,P<0.05);与淋巴细胞凋亡呈负相关关系(r=-0.674,P<0.05);上皮内TGF-β1的表达与上皮细胞凋亡呈正相关关系(r=0.691,P<0.05)结论:1、OLP固有层中CD4+、CD8+T细胞浸润的增加,CD4/CD8比值的变化,说明细胞免疫紊乱在OLP的发生、发展中起一定的作用。2、OLP中上皮细胞及固有层淋巴细胞凋亡存在异常,上皮细胞凋亡增加而固有层淋巴细胞凋亡减少,说明细胞凋亡异常与OLP的发生、发展有一定的关系。3、OLP上皮内Smad7、TGF-β1高表达提示TGF-β1/Smad信号转导通路调节紊乱4、OLP中上皮细胞凋亡增加可能机制为:①TGF-β1/Smad信号通路调节紊乱,TGF-β1高表达可能导致上皮细胞的凋亡增加;②CD8+T细胞增加,凋亡减少,可能使上皮细胞凋亡增加。5、细胞免疫功能紊乱和细胞凋亡异常在OLP的发病中起重要作用。更多还原

【Abstract】 Objective: To evaluate the expression of Smad7, Smad4, TGF-β1, CD4+and CD8+T lymphocytes and the changes of the ratio of CD4/CD8 in oral lichen planus(OLP), and to investigate the role and the relationship of immunological reaction and cell apoptosis in the pathogenesis of oral lichen planus.Methods: Immunohistochemical technique was employed to study the expression of CD4+,CD8+Tcells in specimen from 27 OLP cases and 10 normal oral mucosa (NOM) cases, and the expression of Smad7 ,Smad4, TGF-β1 in 17 OLP cases and 5 NOM cases. TUNEL was used for detecting the cell apoptotic index (AI) in 17 OLP cases. All OLP cases were divided into erosion-atrophy group (13 cases) and non-erosion group (14 cases) according to their clinical features.Results: The amount of CD8+ (35.57±4.25) and CD4+ (17.81±5.13) T cells are obviously elevated in lamina propria of OLP group compared with CD8+ (7.57±3.14) and CD4+ (10.68±4.81) in the NOM(P<0.05). There is a strong significance (P<0.05) when compared the ratio of CD4/CD8 in both group. AI was remarkably increased in epithelia cells (14.26±2.32) and significantly decreased in lymphocytes in lamina propria (8.52±2.34) in OLP cases compared with its expression in the NOM (6.69±0.64) and (20.14±7.27) respectively. The mean stain of TGF-β1 (0.4839±0.2545), Smad7 (0.5852±0.2504) and Smad4(0.3681±0.1827) were analyzed in OLP epithelia cells, in which TGF-β1 and Smad7 demonstrated a strong significance(P<0.05) compared the NOM, but their expression in erosion-type and non-erosion-type of OLP showed no significant difference (P>0.05). The amount of CD8+ T cells in OLP was positively correlated with pathological development of OLP(r=0.553,P<0.05),while it has a negative relationship with cell apoptosis of lymphocytes(r=-0.674,P<0.05).There is a positive correlation between TGF-β1 expression and cell apoptosis in epithelial cells (r=0.691,P<0.05).Conclusion: The increased amount of CD4+, CD8+T cells in lamina propria of OLP and the change of ration of CD4/CD8 suggest that immune response is involved in the pathogenesis of OLP. There is a significant difference of cell apoptotic index between epithelial cells and lymphocytes in lamina propria in OLP, which indicated the abnormal cell apoptosis plays an important role in the pathogenesis of OLP. The high expression of Smad7 and TGF-β1 in OLP showed that TGF-β1/Smad normal pathway was disturbed. Elevated production with low apoptosis in CD8 + T cells in lymphocytes and high expression of TGF-β1 in epithelial cells together with the imbalance of TGF-β1/Smad pathway may all contribute in the mechanisms of cell apoptosis of epithelial cells in OLP. Dysfunctional immune response and abnormal cell apoptosis may play important roles in the pathogenesis of OLP.更多还原