凋亡细胞诱导鼻黏膜上皮细胞增殖参与鼻息肉术后复发中机制研究

Chronic rhinosinusitis with nasal polyps is a common disease of the otorhinolaryngology. However, the recurrence rate is still high after functional endoscopic sinus surgery, however the mechanism of recurrence is not yet clear. We found that compared with preoperative nasal polyps tissues, apoptosis-related protein caspase-3 and its downstream pathway iPLA2-AA-PGE2 axis unregulated in postoperative recurrence of nasal polyps and vesicles tissue, and the proliferation rate was higher in postoperative tissues. Otherwise, the procedure could be induced by pathway PKCδ-Akt-VEGF. We have cultured primary nasal epithelial cells and fibroblasts, and established models of nasal epithelial cells proliferation induced by human respiratory fibroblast apoptosis which caused by changes of microenvironment after surgery. This project intends to use siRNA and inhibitor to intervene the expression of caspase-3 ,iPLA2 or PKCδon the basis of the previous work. At the cellular level, the two pathways in the apoptosis of the cells induced proliferation of nasal mucosal epithelial cells, and its role in postoperative recurrence of nasal polyps. This project has a solid foundation and good continuity. It may provide a new target for the prediction and control of postoperative recurrence of nasal polyps.

慢性鼻-鼻窦炎伴鼻息肉是耳鼻咽喉科常见病，然而功能性鼻窦内窥镜手术术后复发率较高但复发机制尚不明确。我们发现术后复发的鼻息肉及囊泡较术前息肉组织中凋亡相关蛋白caspase-3表达上调，其下游通路iPLA2-AA-PGE2轴表达上调，且复发组织中上皮细胞增殖能力增加，另外这一过程也可能通过PKCδ-Akt-VEGF通路活化所诱导。前期工作中我们建立了原代鼻黏膜上皮细胞及成纤维细胞体外培养模型，以及CRSwNP术后微环境改变诱导细胞凋亡体外模型。本项目拟在前期工作基础上，应用siRNA与拮抗剂干预caspase3,iPLA2，PKCδ的表达，在细胞水平上，研究上述通路如何参与细胞的凋亡诱导鼻黏膜上皮细胞的增殖，以及其在鼻息肉术后复发中的作用。本项目基础扎实，延续性好，可能为预测以及控制鼻息肉术后复发提供新的靶标。

慢性鼻-鼻窦炎伴鼻息肉是耳鼻咽喉科常见病，然而功能性鼻窦内窥镜手术术后复发率较.高但复发机制尚不明确。我们发现术后复发的鼻息肉及囊泡较术前息肉组织中凋亡相关蛋白ca.spase-3表达上调，其下游通路iPLA2-AA-PGE2轴表达上调，且复发组织中上皮细胞增殖能力增.加，另外这一过程也可能通过PKCδ-Akt-VEGF通路活化所诱导。前期工作中我们建立了原代鼻.黏膜上皮细胞及成纤维细胞体外培养模型，以及CRSwNP术后微环境改变诱导细胞凋亡体外模型.。本项目拟在前期工作基础上，应用siRNA与拮抗剂干预caspase3,iPLA2，PKCδ的表达，在细.胞水平上，研究上述通路如何参与细胞的凋亡诱导鼻黏膜上皮细胞的增殖，以及其在鼻息肉术.后复发中的作用。本项目基础扎实，延续性好，可能为预测以及控制鼻息肉术后复发提供新的.靶标。