嚼食檳榔是造成口腔黏膜下纖維化的主要原因，其會造成黏膜上皮萎縮與過量的膠原蛋白堆積在結締組織層中。檳榔素是檳榔中含量最多的植物鹼，其亦被認為與口腔黏膜下纖維化(OSF)關係密切，以往有關此類研究多從膠原蛋白著手，鮮少有研究探討檳榔成分對第一型胞漿素原活化抑制劑的影響。本研究發現 OSF 較人類正常頰黏膜組織有著大量type I plasminogen activator inhibitors (PAI-1)表現，arecoline可提高正常頰黏膜纖維母細胞PAI-1的表達，且在病理切片以免疫組織化學染色法亦發現 PAI-1在OSF較正常組織有明顯的表現。從本研究結果發現檳榔可能透過此一機轉造成正常黏膜轉變成黏膜下纖維化症。
Type I plasminogen activator inhibitor (PAI-1) is a 50 kDa glycoprotein belonging to the serine protease superfamily. PAI-1 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare PAI-1 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induce PAI-1 expression. Twenty-five OSF specimens and six normal buccal mucosa were examined by immunohistochemistry. The activity of PAI-1 from cells cultured from OSF and normal buccal mucosa were using reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blots. PAI-1 expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. In addition, OSF exhibits higher PAI-1 expression than normal buccal mucosa fibroblast (BMF) both in mRNA and protein levels. To verify whether arecoline, a major areca nut alkaloid, could affect PAI-1 expression by human BMFs, RT-PCR and Western blots were used. The results demonstrated highly elevated PAI-1 mRNA and protein expression in normal human BMFs stimulated by arecoline. Taken together, these results suggest that PAI-1 expression is significantly upregulated in OSF tissues from areca quid chewers and arecoline may be responsible for the enhanced PAI-1 expression in vivo.
