Department of Pharmacology, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt.
Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt.
J Pharm Pharmacol. 2024 Jul 5;76(7):788-797. doi: 10.1093/jpp/rgae031.
Intestinal ischemia reperfusion (IIR) is a critical emergency situation that needs immediate intervention. Small intestine is one of the most sensitive tissues to IR injury and it remains a highly morbid condition, with reported mortality rates ranging from 30% to 90%. Thus, we aimed to evaluate the suspected protective role of sacubitril/valsartan (SAC/VAL) on IIR injury.
Thirty-two adult male Wistar rats were used in our model and divided into four groups: sham group, SAC/VAL treated group without IIR, IIR group, and SAC/VAL treated group with IIR. SAC/VAL in a dose of 30 mg/kg was administered orally just before induction of IIR.
SAC/VAL significantly ameliorated IIR-induced changes as it decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), angiotensin II (ANG II), interleukin 6 (IL 6), active caspase 3, and signal transducer- and activator-of transcription (STAT1). However, SAC/VAL administration significantly increased antioxidant parameters such as total antioxidant capacity (TAC), superoxide dismutase (SOD), and reduced glutathione (GSH). Moreover, alteration of the histological structure was observed in IIR group that was improved by SAC/VAL.
SAC/VAL prevents IIR-induced damage via modulation of renin angiotensin aldosterone system, antioxidant, anti-apoptotic, anti-inflammatory properties, and regulation of IL6/STAT1 pathway.
肠缺血再灌注（IIR）是一种需要立即干预的危急情况。小肠是对 IR 损伤最敏感的组织之一，它仍然是一种高度病态的情况，报告的死亡率范围为 30%至 90%。因此，我们旨在评估沙库巴曲缬沙坦（SAC/VAL）对 IIR 损伤的可疑保护作用。
我们的模型使用了 32 只成年雄性 Wistar 大鼠，并将其分为四组：假手术组、未发生 IIR 的 SAC/VAL 治疗组、发生 IIR 的 IIR 组和发生 IIR 的 SAC/VAL 治疗组。在诱导 IIR 之前，以 30mg/kg 的剂量口服给予 SAC/VAL。
SAC/VAL 显著改善了 IIR 诱导的变化，因为它降低了丙二醛（MDA）、肿瘤坏死因子-α（TNFα）、血管紧张素 II（ANG II）、白细胞介素 6（IL 6）、活性半胱氨酸天冬氨酸蛋白酶 3 和信号转导和转录激活因子 1（STAT1）。然而，SAC/VAL 给药显著增加了抗氧化参数，如总抗氧化能力（TAC）、超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）。此外，在 IIR 组中观察到组织学结构的改变，SAC/VAL 改善了这种改变。
SAC/VAL 通过调节肾素-血管紧张素-醛固酮系统、抗氧化、抗凋亡、抗炎特性以及调节 IL6/STAT1 通路，防止 IIR 诱导的损伤。
