白血病抑制因子在IgG4相关唾液腺炎中的抗纤维化作用及其机制研究

纤维化是IgG4相关唾液腺炎的重要病理特点，也是导致唾液腺功能减低的主要原因，但其机制尚不明确。我们通过预实验发现白血病抑制因子（LIF）具有抑制唾液腺纤维化的作用，提出“IgG4相关唾液腺炎中，高表达的LIF通过激活STAT3信号通路上调miR-29表达，抑制成纤维细胞表型转化及胶原的合成分泌，从而抑制腺体纤维化”的科学设想；拟采用RT-PCR、免疫荧光等方法，检测IgG4相关唾液腺炎患者血清及病变组织中LIF水平，探讨其在纤维化中的作用；在病变组织及培养的大鼠和人下颌下腺成纤维细胞中，从抑制成纤维细胞增殖迁移、表型转化和胶原合成分泌的角度揭示LIF抗纤维化作用的机制，从整体、细胞和分子水平，明确LIF在IgG4相关唾液腺炎中的作用，探讨以LIF及其相关分子为靶点，评估、监测、治疗该病的可能性。本研究有助于阐明LIF在IgG4相关唾液腺炎腺体纤维化中的作用及机制，为该病的诊治提供新思路。

Fibrosis is not only an important pathological feature of IgG4-related sialadenitis, but also the main cause of salivary gland hypofunction. However, its mechanism has not been studied in-depth. Previously, we found that leukemia inhibitory factor (LIF) might inhibit the fibrosis of salivary gland. Therefore, we hypothesize that in IgG4-related sialadenitis, the up-regulated LIF inhibits fibrotic phenotype as well as collagen production through Stat3-miR-29, and attenuates salivary glands fibrosis. By use of real-time PCR, immunofluorescent, and molecular biology methods, LIF levels in serum and the involved submandibular gland of patients with IgG4-related sialadenitis will be measured, and their correlation with clinicopathological features will be analyzed. The antifibrotic role of LIF will be explored in both the involved salivary tissues as well as the cultured fibroblasts isolated from human and rat submandibular glands, especially on the aspects of inhibiting proliferation, migration, fibrotic phenotype and collagen production. The possibility of using LIF and its related molecules to evaluate, monitor and treat IgG4-related sialadenitis will be discussed. This study will provide new insights into the mechanism of LIF in inhibiting fibrosis during IgG4-related sialadenitis, and suggest novel therapeutic strategy by targeting LIF.