Jeremic Jovana, Nikolic Turnic Tamara, Zivkovic Vladimir, Jeremic Nevena, Milosavljevic Isidora, Srejovic Ivan, Obrenovic Radmila, Jancic Snezana, Rakocevic Milena, Matic Stevan, Djuric Dragan, Jakovljevic Vladimir
Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Clin Exp Pharmacol Physiol. 2018 Jul;45(7):683-693. doi: 10.1111/1440-1681.12930. Epub 2018 Apr 6.
This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.
体内因复合维生素B缺乏导致的同型半胱氨酸（Hcy）水平升高，会促使心脏功能和氧化还原状态发生变化，进而导致心力衰竭。为开展该研究，我们使用了成年雄性Wistar白化大鼠（n = 30；4周龄；体重100±15克）。通过饮食控制使这些动物出现高同型半胱氨酸血症（HHcy）。持续4周，给动物喂食标准啮齿动物饲料（对照组，CF）、富含蛋氨酸且不缺乏B族维生素（即叶酸、B6和B12）的饲料（HMNV）或富含蛋氨酸且缺乏B族维生素的饲料（HMLV）。经过28天的饮食控制后，处死所有动物。分离大鼠心脏，并按照Langendorff技术在逐渐升高的灌注压力下进行逆行灌注。我们发现血清Hcy升高与总体重和心脏重量之间呈负相关。与其他组相比，HMNV组左心室压力最大上升速率显著增加。所有组的左心室收缩压均有显著变化。HHcy会诱导心脏组织重塑，因为中度HHcy与更明显的间质和血管周围纤维化有关。我们的结果表明，不含复合维生素B的高蛋氨酸饮食会导致与HHcy相关的严重负面影响。
