橄榄叶提取物对糖尿病大鼠心脏组织的抗炎、抗氧化和抗细胞凋亡作用。
Anti-inflammatory, anti-oxidant and anti-apoptotic effects of olive leaf extract in cardiac tissue of diabetic rats.
机构信息
Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
出版信息
J Pharm Pharmacol. 2022 Jul 15;74(7):961-972. doi: 10.1093/jpp/rgac019.
OBJECTIVES
Inflammatory process and apoptosis are involved in the pathogenesis of cardiac injury and oxidative damage caused by diabetes mellitus. The cardioprotective effects of standardized aqueous ethanolic olive leaf extract (OLE), metformin (as a cardiovascular protective agent) and valsartan (as an angiotensin receptor blocker) in the streptozotocin-induced diabetic rats were evaluated.
METHODS
Wistar rats divided into control, diabetic, OLE-treated (100, 200 and 400 mg/kg), metformin (300 mg/kg)-treated, valsartan (30 mg/kg)-treated and metformin/valsartan-treated diabetic groups. Biochemical parameters, including malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activates, and the total contents of thiol were measured, and histopathological and gene expression studies were done on cardiac tissues. Fasting blood sugar (FBS) and cardiac injury markers were examined in serum.
KEY FINDINGS
FBS; the serum levels of lactate dehydrogenase (LDH), creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST); and heart tissue MDA levels due to diabetes were significantly alleviated by OLE treatment (effect size; ηp2 = 0.934, 0.888, 0.848, 0.888 and 0.879, respectively), and SOD and CAT activity and the thiol content in heart tissue were significantly increased (effect size; ηp2 = 0.770, 0.749 and 0.753, respectively). Interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and the number of infiltrating inflammatory cells were reduced in cardiac tissues of OLE-treated groups compared with the diabetic rats (effect size; ηp2 = 0.969 and 0.949, respectively). OLE up-regulated BCL2 gene expression and down-regulated BAX gene expression in cardiac tissue (effect size; ηp2= 0.490 and 0.522, respectively).
CONCLUSION
OLE in a dose-dependent manner ameliorates cardiac damage in diabetic cardiomyopathy, perhaps through attenuating inflammation, oxidative stress and apoptosis.
目的
炎症反应和细胞凋亡参与了糖尿病引起的心肌损伤和氧化损伤的发病机制。本研究评估了标准化水醇橄榄叶提取物(OLE)、二甲双胍(一种心血管保护剂)和缬沙坦(一种血管紧张素受体阻滞剂)对链脲佐菌素诱导的糖尿病大鼠的心脏保护作用。
方法
Wistar 大鼠分为对照组、糖尿病组、OLE 治疗组(100、200 和 400mg/kg)、二甲双胍治疗组(300mg/kg)、缬沙坦治疗组(30mg/kg)和二甲双胍/缬沙坦治疗组。测量丙二醛(MDA)水平、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性以及巯基总量等生化参数,并对心脏组织进行组织病理学和基因表达研究。检测血清中空腹血糖(FBS)和心脏损伤标志物。
结果
FBS;血清乳酸脱氢酶(LDH)、肌酸激酶-肌肉/脑(CK-MB)、天冬氨酸氨基转移酶(AST)水平;以及糖尿病引起的心脏组织 MDA 水平均显著降低,OLE 治疗的效果大小分别为ηp2=0.934、0.888、0.848、0.888 和 0.879;心脏组织 SOD 和 CAT 活性以及巯基含量显著增加,效果大小分别为ηp2=0.770、0.749 和 0.753。与糖尿病大鼠相比,OLE 治疗组心脏组织中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和浸润性炎症细胞数量减少,效果大小分别为ηp2=0.969 和 0.949。OLE 上调心脏组织中 BCL2 基因的表达,下调 BAX 基因的表达,效果大小分别为ηp2=0.490 和 0.522。
结论
OLE 以剂量依赖的方式改善糖尿病心肌病中的心脏损伤,可能通过减轻炎症、氧化应激和细胞凋亡。