Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats.
Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats.
复制标题
过度蛋氨酸摄入诱导的高脑结膜结构血症可促进卵巢切除大鼠脑动脉瘤的破裂。
DOI：
10.1186/s12974-016-0634-3
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发表时间：
2016-06-27
影响因子：
9.3
通讯作者：
Nagahiro S
中科院分区：
文献类型：
--
作者：
Korai M;Kitazato KT;Tada Y;Miyamoto T;Shimada K;Matsushita N;Kanematsu Y;Satomi J;Hashimoto T;Nagahiro S
高同型半胱氨酸血症（HHcy）与炎症和血管壁中基质金属蛋白酶-9（MMP-9）表达的升高相关。然而，高同型半胱氨酸在脑动脉瘤的生长和破裂中的作用仍不清楚。对13周龄雌性Sprague-Dawley大鼠进行双侧卵巢切除术和右侧颈总动脉结扎，并喂食8%高盐饮食以诱导脑动脉瘤。两周后结扎双侧肾后动脉。将受试者分为两组，饮用水中添加或不添加蛋氨酸。在另一组实验中，评估了叶酸（FA）对脑动脉瘤的作用。在12周的观察期内，在前交通动脉（AcomA）或Willis环的后半部分观察到动脉瘤破裂导致的蛛网膜下腔出血。过量摄入MET诱导的HHcy显著增加6-8周动脉瘤破裂的发生率。在用MET处理的大鼠的AcomA处，我们观察到M1巨噬细胞促进细胞生长和浸润。此外，MMP-9的mRNA水平，MMP-9与金属蛋白酶组织抑制剂-2的比值，以及白细胞介素-6的水平在这些大鼠中较高。FA治疗消除了MET的作用，表明AcomA的炎症反应和血管降解归因于过量MET摄入引起的HHcy。我们首先证明，在高血压卵巢切除大鼠，高同型半胱氨酸诱导过量摄入MET可能与动脉瘤壁破裂的倾向。本文的在线版本（doi：10.1186/s12974-016-0634-3）包含补充材料，可供授权用户使用。
Hyperhomocysteinemia (HHcy) is associated with inflammation and a rise in the expression of matrix metalloproteinase-9 (MMP-9) in the vascular wall. However, the role of HHcy in the growth and rupture of cerebral aneurysms remains unclear. Thirteen-week-old female Sprague-Dawley rats were subject to bilateral ovariectomy and ligation of the right common carotid artery and fed an 8 % high-salt diet to induce cerebral aneurysms. Two weeks later, they underwent ligation of the bilateral posterior renal arteries. They were divided into two groups and methionine (MET) was or was not added to their drinking water. In another set of experiments, the role of folic acid (FA) against cerebral aneurysms was assessed. During a 12-week observation period, subarachnoid hemorrhage due to aneurysm rupture was observed at the anterior communicating artery (AcomA) or the posterior half of the circle of Willis. HHcy induced by excessive MET intake significantly increased the incidence of ruptured aneurysms at 6–8 weeks. At the AcomA of rats treated with MET, we observed the promotion of aneurysmal growth and infiltration by M1 macrophages. Furthermore, the mRNA level of MMP-9, the ratio of MMP-9 to the tissue inhibitor of metalloproteinase-2, and the level of interleukin-6 were higher in these rats. Treatment with FA abolished the effect of MET, suggesting that the inflammatory response and vascular degradation at the AcomA is attributable to HHcy due to excessive MET intake. We first demonstrate that in hypertensive ovariectomized rats, HHcy induced by excessive MET intake may be associated with the propensity of the aneurysm wall to rupture. The online version of this article (doi:10.1186/s12974-016-0634-3) contains supplementary material, which is available to authorized users.