Ballerio Rossana, Gianazza Elisabetta, Mussoni Luciana, Miller Ingrid, Gelosa Paolo, Guerrini Uliano, Eberini Ivano, Gemeiner Manfred, Belcredito Silvia, Tremoli Elena, Sironi Luigi
Centro Cardiologico Monzino, IRCCS, Milano, Italy.
Exp Mol Pathol. 2007 Feb;82(1):33-41. doi: 10.1016/j.yexmp.2006.10.001. Epub 2006 Dec 5.
Spontaneously hypertensive stroke-prone rats (SHRSP) feature an established model for human cerebrovascular disease. SHRSP, kept on a high-salt permissive diet (JPD), develop hypertension, renal and brain damage. In this report we compared the behavior of female and male SHRSP regarding the main aspects of their pathological condition. Brain abnormalities, detected by magnetic resonance imaging, developed spontaneously in males after 42+/-3 days, in females after 114+/-14 days from the start of JPD. Survival was >3-fold longer for females than for males. The development of brain damage was preceded, in both genders, by an inflammatory condition characterized by the accumulation in serum and urine of acute-phase proteins. The increase in thiostatin level was significantly lower and delayed in female in comparison to male SHRSP. During JPD female and male SHRSP developed massive proteinuria, its worsening being significantly slower in females. The alterations of vasculature-bound barriers in kidney and brain were connected with endothelial dysfunction and relative deficiency in nitric oxide (NO). In thoracic aortic rings, basal release of NO was significantly higher in female than in male SHRSP, both if receiving and if not receiving JPD. The gender differences in SHRSP thus appear to be connected to a more efficient control in females of inflammation and of endothelial dysfunction.
自发性高血压易中风大鼠（SHRSP）是人类脑血管疾病的一种成熟模型。将SHRSP置于高盐允许饮食（JPD）中，它们会出现高血压、肾脏和脑部损伤。在本报告中，我们比较了雌性和雄性SHRSP在病理状况主要方面的行为。通过磁共振成像检测到的脑部异常，雄性在开始JPD后42±3天自发出现，雌性在114±14天后出现。雌性的存活时间比雄性长3倍以上。在两性中，脑部损伤的发展之前都有炎症状态，其特征是急性期蛋白在血清和尿液中积累。与雄性SHRSP相比，雌性硫抑素水平的升高明显更低且延迟。在JPD期间，雌性和雄性SHRSP都出现大量蛋白尿，但其恶化在雌性中明显较慢。肾脏和脑部血管结合屏障的改变与内皮功能障碍和一氧化氮（NO）相对缺乏有关。在胸主动脉环中，无论是否接受JPD，雌性SHRSP中NO的基础释放都明显高于雄性。因此，SHRSP中的性别差异似乎与雌性对炎症和内皮功能障碍的更有效控制有关。
