Faculty of Medical Sciences, Department of Internal medicine, University of Kragujevac, Kragujevac, Serbia.
Department for Pathological Anatomical Diagnosis, Clinical Center "Kragujevac", Kragujevac, Serbia.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Jan;393(1):99-109. doi: 10.1007/s00210-019-01717-z. Epub 2019 Aug 27.
The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70 cm HO. After a stabilization period, CPP was lowered to 60 cm HO and then gradually increased to 80, 100, 120 and finally decreased to 40 cm HO in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of HO and NO-. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO- in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.
本研究旨在评估高剂量叶酸引起的急性肾损伤对心脏功能和血清及分离大鼠心脏氧化应激标志物的影响。Wistar 白化大鼠的分离心脏（分为两组：对照组和叶酸组）根据 Langendorff 技术在基础冠状动脉灌注压 CPP 为 70cmHO 下进行灌注。稳定期后，将 CPP 降低至 60cmHO，然后逐渐增加至 80、100、120，最后降低至 40cmHO，以建立冠状动脉自动调节。对于每个灌注压力值，确定左心室功能参数。收集冠状静脉流出物样本以测定冠状血流和氧化应激生物标志物。采集血液样本以检查血清尿素、肌酐、Na、K 和氧化应激及抗氧化防御系统参数的值。收集心脏和肾脏组织样本进行组织病理学检查。叶酸组表现出收缩压和舒张压左心室压力降低以及冠状血流增加和左心室压力发展率最低。在冠状血流中，叶酸组显示 TBARS 水平升高和 HO 和 NO-减少。用叶酸处理的大鼠血清 ROS 浓度较低，尤其是 TBARS 和 NO-的浓度明显较低。全身抗氧化应激参数处于明显较高水平，尤其是 SOD 和 GSH。这项研究是对 3 型心肾综合征的实验证实，它代表了引起心脏功能损害的急性肾损伤。数据表明，急性肾损伤对心肌的负面影响不一定涉及氧化应激，这可能导致未来的研究将以炎症为器官串扰的重要因素之一为基础。
