Oboshi Makiko, Naito Yoshiro, Sawada Hisashi, Hirotani Shinichi, Iwasaku Toshihiro, Okuhara Yoshitaka, Morisawa Daisuke, Eguchi Akiyo, Nishimura Koichi, Fujii Kenichi, Mano Toshiaki, Ishihara Masaharu, Masuyama Tohru
Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
PLoS One. 2015 May 11;10(5):e0126611. doi: 10.1371/journal.pone.0126611. eCollection 2015.
Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT.
We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation.
The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet.
These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT.
深静脉血栓形成(DVT)是肺血栓栓塞和猝死的主要原因。因此,了解DVT的病理生理学很重要。最近,有报道称铁与血栓性疾病有关。因此,在本研究中,我们在DVT大鼠模型中研究了饮食铁限制对血栓溶解过程的影响。
我们通过结扎8周龄雄性Sprague-Dawley大鼠的下腔静脉来诱导DVT。然后给这些大鼠喂食正常饮食(DVT组)或铁限制饮食(DVT+IR组)。在结扎后5天采集形成血栓的下腔静脉。
与正常饮食相比,铁限制饮食减小了静脉血栓的大小。与DVT组相比,DVT+IR组血栓内的胶原蛋白含量减少。此外,与DVT组相比,DVT+IR组血栓内基质金属蛋白酶-9的基因表达和活性增加。此外,与DVT组相比,DVT+IR组血栓内的新生血管形成更多,尿激酶型纤溶酶原激活剂和组织型纤溶酶原激活剂的基因表达水平也更高。与正常饮食相比,铁限制饮食减少了血栓内超氧化物的产生。
这些结果表明,饮食铁限制会影响DVT的血栓溶解过程。