雄激素通过HIF-1α调控下肢血管生成的作用对不同性别小鼠下肢缺血预后影响的差异及其机制的研究

Lower extremities ischemic diseases has seriously effect on the life quality of the patients, high rate of disability and even life-threatening..Extensive clinical studies show that men has better prognosis of lower extremities ischemic disease than women. At present, the mechanism of gender difference is still unclear. Our studies have proved gender certainly influences the blood flow recovery in mouse model (Peng XZ et al. Am J Physiol Heart Circ Physiol. 2011). Our previous experiments also suggest that differences are found in the affect of androgen to the prognosis of blood flow recovery in mouse model of different gender, and angiogenesis of endothelial cell. But there’re no differences in estrogen’s affect. Androgen may also involve in adjustment of HIF-1α to angiogenesis. Therefore, we assume that the regulation of androgen through HIF-1α on angiogenesis is the key factor for gender difference on prognosis of hindlimb ischemia. We try to demonstrate following questions on the basis of existing studies: (1) to study affect of androgen on the prognosis of hindlimb ischemia of different gender. (2) to further explore the mechanism that androgen’s regulation of angiogenesis through HIF-1α. This study will contribute to understand the molecular mechanisms of androgen’s effects on angiogenesis, and provide new experimental basis and a new way for clinical diagnosis and treatment of lower extremities extremities disease.

下肢缺血性疾病严重影响患者生活质量、致残率高甚至危及生命。大量临床研究显示下肢缺血性疾病存在男性患者比女性患者预后好的性别差异现象，但机制未明。针对这一临床现象，我们研究发现小鼠下肢缺血预后存在性别差异（Peng XZ et al. Am J Physiol Heart Circ Physiol. 2011）。前期实验还提示雄激素对不同性别小鼠下肢缺血预后和血管内皮细胞血管生成的影响存在差异，而雌激素对不同性别下肢缺血预后的影响无差异。且雄激素可能参与HIF-1α调控血管内皮细胞的血管生成。因此我们考虑雄激素通过HIF-1α调控血管生成是下肢缺血预后性别差异的主要影响因素。我们拟进一步开展以下研究：⑴研究雄激素对不同性别小鼠下肢缺血预后的影响。⑵进一步探讨雄激素通过HIF-1α的调控血管生成的机制。本研究将有助于深入了解雄激素对血管生成的影响的机制，为临床诊治下肢缺血疾病提供新的思路。