Badmus Olufunto O, Olatunji Lawrence A
HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
Department of Public Health, Kwara State University, Malete, Nigeria.
Can J Physiol Pharmacol. 2020 Oct;98(10):667-677. doi: 10.1139/cjpp-2018-0351. Epub 2020 Apr 7.
Glucocorticoid therapy has been associated with adverse cardiometabolic effects during pregnancy. Inflammation-mediated cardiac dysfunction, an independent risk factor for morbidity and mortality, has been linked to defective glucose-6-phosphate dehydrogenase (G6PD) dependent antioxidant defenses and increased endoglin expression. We therefore sought to investigate the effects of dexamethasone (DEX) on cardiac endoglin and G6PD-dependent antioxidant defense. Twenty-four rats were randomly assigned to nonpregnant (PRE(-)), DEX-exposed nonpregnant (PRE(-) + DEX), pregnant (PRE(+)), and DEX-exposed pregnant (PRE(+) + DEX) rats, respectively ( = 6 per group). PRE(-) and PRE(+) rats received vehicle (per oral (po)), while PRE(-) + DEX and PRE(+) + DEX groups were administered DEX (0.2 mg/kg po) between gestational days 14 and 19, respectively. Results showed that DEX caused increased cardiac pro-inflammatory markers (adenosine deaminase (ADA) activity, endoglin, vascular cell adhesion molecule-1 (VCAM-1), tissue injury markers (LDH, GGT, AST, ALT, and ALP), metabolic disturbances (elevated fasting plasma glucose, free fatty acid (FFA), lactate, cardiac FFA, and lactate) and depressed G6PD-dependent antioxidant defenses (G6PD activity, reduced glutathione/oxidized glutathione ratio, and nitric oxide) in pregnant and nonpregnant rats. The present study demonstrates that DEX led to increased cardiac endoglin and VCAM-1 that is accompanied by defective G6PD-dependent antioxidant defenses but not cardiac lipid accumulation in both pregnant and nonpregnant rats.
糖皮质激素治疗与孕期不良心脏代谢效应有关。炎症介导的心脏功能障碍是发病和死亡的独立危险因素，与葡萄糖-6-磷酸脱氢酶（G6PD）依赖性抗氧化防御缺陷及内皮糖蛋白表达增加有关。因此，我们试图研究地塞米松（DEX）对心脏内皮糖蛋白和G6PD依赖性抗氧化防御的影响。将24只大鼠随机分为未孕（PRE(-)）、DEX暴露未孕（PRE(-)+DEX）、孕鼠（PRE(+)）和DEX暴露孕鼠（PRE(+)+DEX）四组（每组n = 6）。PRE(-)和PRE(+)组大鼠接受赋形剂（口服），而PRE(-)+DEX组和PRE(+)+DEX组分别在妊娠第14至19天给予DEX（0.2 mg/kg口服）。结果显示，DEX导致孕鼠和未孕大鼠心脏促炎标志物（腺苷脱氨酶（ADA）活性、内皮糖蛋白、血管细胞黏附分子-1（VCAM-1））、组织损伤标志物（乳酸脱氢酶、γ-谷氨酰转移酶、天冬氨酸转氨酶、丙氨酸转氨酶和碱性磷酸酶）、代谢紊乱（空腹血糖、游离脂肪酸（FFA）、乳酸、心脏FFA和乳酸升高）以及G6PD依赖性抗氧化防御降低（G6PD活性、还原型谷胱甘肽/氧化型谷胱甘肽比值和一氧化氮）。本研究表明，DEX导致孕鼠和未孕大鼠心脏内皮糖蛋白和VCAM-1增加，同时伴有G6PD依赖性抗氧化防御缺陷，但未出现心脏脂质蓄积。
