脂质炎症介质LTB4通过其高亲和性受体BLT1，在免疫炎症性疾病中发挥重要生物学功能。肌成纤维细胞在系统性硬化症（SSc）发病中作用关键，但调控机制不明。本课题前期发现：LTB4在SSc患者外周血中上调；BLT1在博来霉素（BLM）诱导的SSc小鼠皮肤中亦升高；而在BLT1基因缺失（BLT1-/-）小鼠中，BLM不能诱导出SSc表型，且皮肤和肺中α-SMA+肌成纤维细胞较野生型明显减少，提示LTB4/BLT1轴参与SSc发病，LTB4可能经BLT1调控肌成纤维细胞形成。本研究通过微渗透压泵传输BLM的方法建立了改良SSc小鼠模型，拟采用BLT1-/-小鼠和BLT1拮抗剂干预，明确LTB4/BLT1轴对SSc发病的作用，通过原代细胞培养体外研究成纤维细胞-肌成纤维细胞转化和脂肪细胞-肌成纤维细胞转化，以阐明LTB4/BLT1轴调控肌成纤维细胞形成参与SSc发病的机制，为临床转化提供理论借鉴。

Leukotriene B4 (LTB4), a lipid mediator of inflammation, plays a key role in the autoimmune and inflammatory diseases via its high affinity receptor BLT1. Myofibroblast is recognized to be critical in the progression of systemic sclerosis (SSc), but the mechanism is still unknown. In our previous study, LTB4 was observed to be up-regulated in the serum of SSc patients. The level of BLT1 was also increased in the skin tissues of SSc mice induced by bleomycin (BLM). BLT1-/- mice did not manifest the phenotype of SSc following the BLM treatment. And the reduction of α-SMA+ myofibroblasts was also found in the skin and lung tissues of BLT1-/- mice following the administration of BLM, compared with those in wide type mice. These findings indicated LTB4/BLT1 axis participated in the progression of SSc, and LTB4 may play its regulatory role via BLT1 in myofibroblast formation. We have already established a modified SSc mouse model by delivering BLM via an osmotic mini-pump. We plan to use BLT1-/- mice and BLT1 specific inhibitor to reveal the contribution of LTB4/BLT1 axis to the progression of SSc. Also we will study fibroblast-myofibroblast transition and adipocyte-myofibroblast transition in vitro using primary cell culture. In this way, we will try to elucidate the mechanism that LTB4/BLT1 axis may take part in the development of SSc by regulating myofibroblast formation. Taken together, these study will hopefully supply the theoretical basis for the clinical transition in SSc.