Al-Kouh Aisha, Babiker Fawzi, Al-Bader Maie
Department of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Kuwait City 13110, Kuwait.
Pharmaceuticals (Basel). 2023 Feb 3;16(2):238. doi: 10.3390/ph16020238.
Diabetes mellitus (DM) is a risk factor for cardiovascular diseases, specifically, the ischemic heart diseases (IHD). The renin-angiotensin system (RAS) affects the heart directly and indirectly. However, its role in the protection of the heart against I/R injury is not completely understood. The aim of the current study was to evaluate the efficacy of the angiotensin-converting enzyme (ACE) inhibitor and Angiotensin II receptor (AT1R) blocker or a combination thereof in protection of the heart from I/R injury.
Hearts isolated from adult male Wistar rats ( = 8) were subjected to high glucose levels; acute hyperglycemia or streptozotocin (STZ)-induced diabetes were used in this study. Hearts were subjected to I/R injury, treated with Captopril, an ACE inhibitor; Losartan, an AT1R antagonist; or a combination thereof. Hemodynamics data were measured using a suitable software for that purpose. Additionally, infarct size was evaluated using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. The levels of apoptosis markers (caspase-3 and -8), antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), nitric oxide synthase (eNOS), and glucose transporter type 4 (GLUT-4) protein levels were evaluated by Western blotting. Pro-inflammatory and anti-inflammatory cytokines levels were evaluated by enzyme-linked immunosorbent assay (ELISA).
Captopril and Losartan alone or in combination abolished the effect of I/R injury in hearts subjected to acute hyperglycemia or STZ-induced diabetes. There was a significant ( < 0.05) recovery in hemodynamics, infarct size, and apoptosis markers following the treatment with Captopril, Losartan, or their combination. Treatment with Captopril, Losartan, or their combination significantly ( < 0.05) reduced pro-inflammatory cytokines and increased GLUT-4 protein levels.
The blockade of the RAS system protected the diabetic heart from I/R injury. This protection followed a pathway that utilizes GLUT-4 to decrease the apoptosis markers, pro-inflammatory cytokines, and to increase the anti-inflammatory cytokines. This protection seems to employ a pathway which is not involving ERK1/2 and eNOS.
糖尿病（DM）是心血管疾病的危险因素，尤其是缺血性心脏病（IHD）。肾素-血管紧张素系统（RAS）直接或间接影响心脏。然而，其在保护心脏免受缺血/再灌注（I/R）损伤中的作用尚未完全明确。本研究的目的是评估血管紧张素转换酶（ACE）抑制剂和血管紧张素II受体（AT1R）阻滞剂或两者联合使用对心脏I/R损伤的保护作用。
从成年雄性Wistar大鼠（n = 8）分离心脏，使其处于高血糖水平；本研究采用急性高血糖或链脲佐菌素（STZ）诱导的糖尿病模型。对心脏进行I/R损伤，并用ACE抑制剂卡托普利、AT1R拮抗剂氯沙坦或两者联合进行治疗。使用合适的软件测量血流动力学数据。此外，采用2,3,5-氯化三苯基四氮唑（TTC）染色评估梗死面积。通过蛋白质印迹法评估凋亡标志物（半胱天冬酶-3和-8）、抗氧化酶超氧化物歧化酶（SOD）和过氧化氢酶（CAT）、一氧化氮合酶（eNOS）以及葡萄糖转运蛋白4（GLUT-4）的蛋白水平。通过酶联免疫吸附测定（ELISA）评估促炎和抗炎细胞因子水平。
卡托普利和氯沙坦单独或联合使用消除了急性高血糖或STZ诱导糖尿病心脏中I/R损伤的影响。用卡托普利、氯沙坦或其联合治疗后，血流动力学、梗死面积和凋亡标志物有显著（P < 0.05）恢复。用卡托普利、氯沙坦或其联合治疗显著（P < 0.05）降低了促炎细胞因子水平并增加了GLUT-4蛋白水平。
RAS系统的阻断保护糖尿病心脏免受I/R损伤。这种保护作用通过利用GLUT-4减少凋亡标志物、促炎细胞因子并增加抗炎细胞因子的途径实现。这种保护作用似乎采用了不涉及细胞外信号调节激酶1/2（ERK1/2）和eNOS的途径。
