氯沙坦预防及治疗氯化钙诱导的小鼠腹主动脉瘤的机制探讨

Losartan prevents from the formation and interferes with the development of calcium chloride-induced abdominal aortic aneurysms

目的探讨血管紧张素ⅡⅠ型受体抑制剂氯沙坦预防及治疗氯化钙诱导的腹主动脉瘤的作用机制。方法选用血管旁孵育高浓度氯化钙诱发的小鼠腹主动脉瘤模型,利用病理学以及血管超声学等方法进行研究。结果预防性地给予氯沙坦不仅能够抑制血管扩张,减小血管的最大外径,保护血管结构完整;同时对于已经形成的腹主动脉瘤,氯沙坦还能够阻止其进行性发展。结论氯沙坦预防并治疗腹主动脉瘤的作用可能与其能够调节血管组织局部免疫微环境并且抑制炎性细胞浸润,减轻血管损伤,调节血管重构及改善纤维化的程度有关。氯沙坦可能是阻止腹主动脉瘤发生发展潜在的治疗药物。

Objective Abdominal aortic aneurysm（AAA）,a chronic inflammatory vascular disorder,results in progressive expansion and rupture of the aorta with high mortality among the elderly.Multiple factors contribute to the pathogenesis of AAA that somehow induces aneurysmal manifestations.There are no effective drugs available currently.This study aims to find out whether losartan,an angiotensin Ⅱ type 1 receptor（AT1） antagonist,can prevent and treat the CaCl2-induced AAA.Methods We chose periaortic application of 0.5 mol/L CaCl2-induced mouse AAA model.Ultrasonographic and histological studies were conducted to evaluate the formation of AAA in mice.Results Losartan not only protected against the formation of AAA,but also hindered the development of AAA.Losartan reduced aortic expansion and elastic lamina degradation.Conclusion The prophylactic and therapeutic effects of losartan are associated with the regulation of vascular fibrosis and inflammation.Losartan inhibits the infiltration of inflammatory cells and decreases the expression of several cytokines in the vascular tissue of AAA.Our studies will provide insight into the pathogenesis of AAA induced by CaCl2 and offer more evidence that losartan has a great potential for the development of therapeutic agents against AAA.