Department of Nephrology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Department of Rheumatology and Immunology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Int J Biol Macromol. 2018 Nov;119:565-571. doi: 10.1016/j.ijbiomac.2018.07.149. Epub 2018 Jul 25.
In this study, the protective effect of valsartan against glycerol-induced acute kidney injury (AKI) in male albino rats was investigated. Valsartan is used to treat high blood pressure and congestive heart failure and can prolong lifespan following a heart attack. The rats were divided into control, AKI, AKI + valsartan 100 mg/kg bw, and AKI + valsartan 200 mg/kg bw groups. Superoxide dismutase, glutathione peroxidase, catalase, lipid peroxidation, and reduced glutathione were assessed, and histopathological, immunohistochemical and western blot analyses were performed. Valsartan supplementation in AKI rats substantially increased superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels but reduced the level of lipid peroxidation. Valsartan significantly reduced the severity of the renal tubular injury, renal lesions, and necrosis. Valsartan decreased NF-κB and TLR4 mRNA expression by >50% and their protein levels by >40%. Therefore, valsartan supplementation inhibited glycerol-induced functional and pathological damage to the kidney in a concentration-dependent manner. We propose that valsartan protects rat kidney tissue by downregulating NF-κB and TLR4 expression.
本研究旨在探讨缬沙坦对雄性白化大鼠甘油诱导的急性肾损伤（AKI）的保护作用。缬沙坦用于治疗高血压和充血性心力衰竭，并可延长心脏病发作后的寿命。将大鼠分为对照组、AKI 组、AKI+缬沙坦 100mg/kg bw 组和 AKI+缬沙坦 200mg/kg bw 组。评估超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶、脂质过氧化和还原型谷胱甘肽的水平，并进行组织病理学、免疫组织化学和 Western blot 分析。在 AKI 大鼠中补充缬沙坦可显著增加超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽的水平，但降低脂质过氧化水平。缬沙坦显著减轻了肾小管损伤、肾病变和坏死的严重程度。缬沙坦使 NF-κB 和 TLR4 mRNA 表达降低超过 50%，蛋白水平降低超过 40%。因此，缬沙坦以浓度依赖的方式抑制甘油诱导的肾脏功能和病理损伤。我们提出，缬沙坦通过下调 NF-κB 和 TLR4 的表达来保护大鼠的肾脏组织。
