脂联素拮抗瘦素致血管细胞外基质（ECM）重构的作用研究

肥胖患者的脂肪组织可以过度分泌瘦素，研究表明瘦素过多可以导致肝脏、肾脏和心肌细胞的纤维化，这是瘦素诱导的细胞外基质（ECM）重构（胶原生成与降解失衡）造成的。我们前期研究显示瘦素可以使三维培养的血管内皮细胞（VECs）和血管平滑肌细胞（VSMCs）的Ⅱ型胶原表达增加以及MMP-2的表达下降。为了进一步证实瘦素可以导致血管ECM重构，本项目体外部分在三维血管模型中加入瘦素，体内部分在ob/ob小鼠（瘦素缺乏肥胖小鼠）中泵入瘦素，然后观察血管ECM重构发生。其次，我们之前的研究显示脂联素可以拮抗瘦素的致血管炎症作用，因此在本项目中我们继续观察脂联素是否可以减弱瘦素的致血管ECM重构作用。最后，用免疫印迹法检测脂联素是否通过激活AMPK途径增加SOCS- 3（细胞因子信号传递抑制体-3）的表达，而后者是瘦素JAK2/STAT3途径的抑制物，这有望阐明脂联素抑制瘦素致血管ECM重构的分子机制。

Leptin was excessively secreted by adipose tissue of obese patients. Studies had shown that excessive leptin could lead to the fibrosis of the liver, kidney and myocardial cells, which was the results of leptin-induced extracellular matrix (ECM) remodeling( imbalance of collagen synthesis and degradation). Our previous studies had shown that leptin could increase the expression of collagen II and reduce the expression of MMP-2 in vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) which was co-cultured in the three-dimensional(3D) co-culture model. To confirm that leptin can cause vascular ECM remodeling, we will add leptin into the 3D co-culture model in vitro and pump leptin into the body of ob / ob mice (leptin deficiency obese mice) in vivo and then observe the occurrence of the vascular ECM remodeling. Secondly, we had also found that adiponectin could antagonize leptin-induced vascular inflammation. So in this project, we will continue to observe whether adiponectin could alleviate leptin-induced vascular ECM remodeling. Finally, Western blot will be used to detect whether adiponectin could increase the expression of the SOCS-3 (Suppressors of Cytokine signaling ) by activating the AMPK pathway. Because SOCS-3 was one of the inhibitors of the JAK2/STAT3 pathway which was activated by leptin, it is expected to reveal the molecular mechanisms of how adiponectin inhibits leptin-induced vascular ECM remodeling.