Grzelak Norbert, Kaczmarek Dominik, Poziemba Krystian Marek, Mrówczyński Włodzimierz
Department of Neurobiology, Poznań University of Physical Education, Poznań, Poland.
Department of Physiology and Biochemistry, Poznań University of Physical Education, Poznań, Poland.
Diabetes Metab Syndr Obes. 2024 Dec 5;17:4649-4660. doi: 10.2147/DMSO.S486807. eCollection 2024.
The study aimed to determine whether heterozygous BDNF-deficient (BDNF-knockout, SD-BDNF) rats exhibit pathological changes in the myocardium and to assess whether a 5-week moderate-intensity endurance training program can reverse adverse changes in the heart muscle.
Experiments were conducted on four groups of rats: control wild-type, control BDNF knockout, trained wild-type and trained BDNF knockout. Knockout rats were selected due to the presence of symptoms resembling metabolic syndrome in serum and liver while 5-week moderate endurance training was used as an intervention targeted at restoring heart function. Measurements of BDNF/Trk-B concentrations and molecules levels and activities, such as cardiac specific enzymes like creatine kinase and creatine kinase myocardial band, lipids as total cholesterol, low-density lipoprotein and triglycerides, metabolic enzymes including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and lactate dehydrogenase and interleukin-1 were carried out in myocardium homogenates.
In BDNF-deficient rats, the myocardium showed significantly reduced lipid concentrations, decreased metabolic and cardiac enzyme activity, and elevated Trk-B levels, all of which are indicative of myocardial ischemia or hypoxia. These changes in critical biomarkers were consistent with those earlier observed in the livers of BDNF-deficient rats, suggesting a link between the liver and cardiac function. Moderate endurance training led to an increase in creatine kinase activity in the myocardium of trained rats, suggesting increased production and utilization of energy required for myocardial contraction in trained wild-type and knockout populations of rats.
BDNF-deficient rats exhibited numerous myocardial abnormalities, most of which were not reversible after moderate-intensity endurance training. These findings provide a basis for a deeper understanding of the mechanisms underlying myocardial disorders in BDNF-deficient rats, which appear to be a suitable model for studying various aspects of metabolic disorders.
本研究旨在确定杂合型脑源性神经营养因子缺陷(BDNF基因敲除,SD-BDNF)大鼠的心肌是否出现病理变化,并评估为期5周的中等强度耐力训练计划能否逆转心肌的不良变化。
对四组大鼠进行实验:对照野生型、对照BDNF基因敲除型、训练野生型和训练BDNF基因敲除型。选择基因敲除大鼠是因为其血清和肝脏中存在类似代谢综合征的症状,而将为期5周的中等耐力训练用作恢复心脏功能的干预措施。在心肌匀浆中测量BDNF/Trk-B浓度以及分子水平和活性,如肌酸激酶和肌酸激酶同工酶等心脏特异性酶、总胆固醇、低密度脂蛋白和甘油三酯等脂质、丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶和乳酸脱氢酶等代谢酶以及白细胞介素-1。
在BDNF缺陷大鼠中,心肌脂质浓度显著降低,代谢酶和心脏酶活性下降,Trk-B水平升高,所有这些均表明心肌缺血或缺氧。这些关键生物标志物的变化与早期在BDNF缺陷大鼠肝脏中观察到的变化一致,表明肝脏与心脏功能之间存在联系。中等强度耐力训练导致训练大鼠心肌中的肌酸激酶活性增加,表明训练的野生型和基因敲除型大鼠群体中心肌收缩所需能量的产生和利用增加。
BDNF缺陷大鼠表现出许多心肌异常,其中大多数在中等强度耐力训练后不可逆转。这些发现为更深入了解BDNF缺陷大鼠心肌疾病的潜在机制提供了基础,BDNF缺陷大鼠似乎是研究代谢紊乱各个方面的合适模型。