尽管心肌细胞凋亡加速是心脏损伤的主要原因之一,潜在的机制仍然未知。除了检查比索洛尔和地奥司明对CoCl2引起的心脏损伤的潜在保护作用外,这项研究的目的是确定调节氯化钴(CoCl2)引起的缺氧心脏损伤的潜在机制。从实验的第一天起,除了Cocl214天,为期21天,将大鼠分为以下几组:正常对照组,大鼠仅接受媒介物(2ml/kg/天,p.o.),(Cocl2,150毫克/千克/天,p.o.),比索洛尔(25毫克/千克/天,p.o.);地奥司明(100毫克/千克/天,p.o.)和比索洛尔+地奥司明+Cocl2组。在实验期结束时,血清用于评估心功能,血脂谱,和促炎/抗炎细胞因子。此外,收集组织样本用于评估氧化应激,内皮功能障碍,α-SMA,PKC-α,MiR-143-3P,MAPK,ERK5、MCP-1、CXCR4、Orai-1和STIM-1。地奥司明和比索洛尔,无论是单独还是组合,通过减少心电图异常和CoCl2引起的低血压来增强心脏功能。此外,它们通过下调α-SMA的心脏表达显著改善内皮功能障碍,PKC-α,MiR-143-3P,MAPK,ERK5、MCP-1、CXCR4、Orai-1和STIM-1。比索洛尔和地奥司明产生针对炎症状态的调节活性,氧化还原平衡,和动脉粥样硬化指数同时发生。一起,地奥司明和比索洛尔,无论是单独还是组合,可显着减少CoCl2引起的所有心脏改变。阻碍缺氧诱导的α-SMA的能力,PKC-α,MiR-143-3P/MAPK/MCP-1,MiR-143-3P/ERK5/CXCR4,Orai-1/STIM-1信号激活,以及他们的抗炎,抗氧化剂,和抗凋亡特性,可能是这些心脏保护结果的原因。
Even while accelerated cardiomyocyte apoptosis is one of the primary causes of cardiac damage, the underlying mechanism is still mostly unknown. In addition to examining potential protective effects of bisoprolol and diosmin against CoCl2-induced cardiac injury, the goal of this study was to identify potential mechanisms regulating the hypoxic cardiac damage caused by cobalt chloride (CoCl2). For a period of 21 days except Cocl2 14 days from the first day of the experiment, rats were split into the following groups: Normal control group, rats received vehicle only (2 ml/kg/day, p.o.), (Cocl2, 150 mg/kg/day, p.o.), bisoprolol (25 mg/kg/day, p.o.); diosmin (100 mg/kg/day, p.o.) and bisoprolol + diosmin + Cocl2 groups. At the end of the experimental period, serum was taken for estimation of cardiac function, lipid profile, and pro/anti-inflammatory cytokines. Moreover, tissue samples were collected for evaluation of oxidative stress, endothelial dysfunction, α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Diosmin and bisoprolol, either alone or in combination, enhance heart function by reducing abnormalities in the electrocardiogram and the hypotension brought on by CoCl2. Additionally, they significantly ameliorate endothelial dysfunction by downregulating the cardiac expressions of α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Bisoprolol and diosmin produced modulatory activity against inflammatory state, redox balance, and atherogenic index concurrently. Together, diosmin and bisoprolol, either alone or in combination, significantly reduced all the cardiac alterations brought on by CoCl2. The capacity to obstruct hypoxia-induced α-SMA, PKC-α, MiR-143-3P/MAPK/MCP-1, MiR-143-3P/ERK5/CXCR4, Orai-1/STIM-1 signaling activation, as well as their anti-inflammatory, antioxidant, and anti-apoptotic properties, may be responsible for these cardio-protective results.