原发性干燥综合征唇腺组织中细胞凋亡及相关基因表达的研究

Apoptosis and related gene expression in minor labial salivary gland of patients with primary Sjogren′s syndrome

目的研究原发性干燥综合征(primarySj觟gren'ssyndrome,pSS)患者唇腺组织上皮细胞凋亡及相关基因表达与pSS组织损伤的关系。方法应用原位末端标记及免疫组织化学的方法,对30例pSS患者及10例对照唇腺组织中凋亡细胞及Fas、FasL、Bc1-2相关基因蛋白的表达进行检测和组织细胞定位。结果pSS患者唇腺组织中腺泡上皮细胞(AEC)及导管上皮细胞(DEC)凋亡率均明显高于对照组(P<0.001),而浸润的单核细胞(IMC)凋亡率与对照组相比差异无显著性(P>0.05)。pSS患者唇腺AEC、DEC及IMC中,Fas阳性表达的细胞百分比均明显高于对照组(P<0.001),并与细胞凋亡率呈正相关(r=0.431,0.415,0.804;P<0.05);FasL阳性表达的细胞百分比均明显高于对照组(P<0.001),并与细胞凋亡率呈正相关(r=0.654,0.619,0.489;P<0.01);Bcl-2阳性表达的细胞百分比,AEC和DEC均明显低于对照组(P<0.05),而IMC明显高于对照组(P<0.001),DEC和IMC与细胞凋亡率呈负相关(r=-0.400,-0.364;P<0.05),但AEC与细胞凋亡率无相关性(r=-0.329,P>0.05)。结论pSS患者唇腺组织中上皮细胞凋亡增加和淋巴细胞凋亡减少可能是导致腺体破坏进而功能丧失的原因之一;Fas、FasL增加及Bcl-2减少皆与促进细胞凋亡有关;Bcl-2在pSS唇腺IMC中表达增加暗示IMC似乎逃脱凋亡,形成炎性浸润灶。

Objective To study the roles of apoptosis and expression of the related genes in minor labial salivary gland of patients with primary Sjogren′s syndrome (pSS). Methods Biopsies of minor submucosal labial salivary gland (SG) were obtained from 30 patients with pSS and 10 control individuals. The in situ end labeling and immunohistochemical staining were used to detect the apoptotic cells and the expression of Fas, FasL and Bcl-2. Results The percentage of apoptotic acinar and ductal epithelial cells (AEC and DEC) in labial salivary glands of patients with pSS was significantly higher than that of control respectively, but the percentage of apoptotic infiltrating mononuclear cells (IMC) showed no significant difference compared with that of control, pSS AEC and DEC showed increased expression of Fas/FasL and decreased expression of Bcl-2, whereas pSS IMC showed increased expression of Fas, Fas/FasL and Bcl-2. There was significant positive correlation between the percentage of apoptotic cells and the cells expressing Fas and FasL in pSS AEC DEC and IMC, respectively, and there was significant negative correlation between the percentage of the apoptotic cells and that of cells expressing Bcl-2 in pSS DEC and IMC, but there wasn′t correlation between the percentage of the apoptotic cells and that of cells expressing Bcl-2 in pSS AEC. Conclusions The apoptotic cells increased in the epithelial cells and decreased in IMC of the labial salivary glands may be one of the mechanisms leading to the glandular destruction found in pSS. In pSS labial salivary glands, the expression of Fas and FasL may promote apoptosis, while the expression of Bcl-2 may inhibit apoptosis. The increased expression of Bcl-2 in pSS IMC indicates that IMC may be able to escape apoptosis, resulting in inflammatory cell foci.