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吉非贝齐,一种降脂药物,可改善衰老小鼠模型的肝肾功能损伤。

Gemfibrozil, a lipid-lowering drug, improves hepatorenal damages in a mouse model of aging.

机构信息

Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

出版信息

Fundam Clin Pharmacol. 2023 Jun;37(3):599-605. doi: 10.1111/fcp.12865. Epub 2023 Jan 14.

Abstract

Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on peroxisome proliferator-activated receptor-α (PPAR-α) and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti-inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal damages in a D-galactose (D-gal)-induced aging model. We used 28 male mice, which were equally and randomly divided into four groups as follows: normal, D-gal (150 mg/kg/day; intraperitoneal [i.p.], for 6 weeks), GFZ (100 mg/kg/day GFZ, orally [p.o.] for 6 weeks), and the combined D-gal + GFZ. Liver and kidney function indices were measured as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase. Oxidative stress in hepatic and renal tissue was evaluated through malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. Finally, the liver and kidney tissues were assessed for histopathological lesions. The results showed that D-gal-induced aging leads to abnormalities in liver and kidney function indices. D-gal also induced significant oxidative stress and histopathological lesions in these organs. GFZ improved function indices and oxidative stress compared to the D-gal-treated animals. Histological evaluations of the liver and kidney also confirmed these results. These data provide evidence for the potential therapeutic of GFZ in clinical practice for mitigating the hepatorenal damages of aging.

摘要

吉非贝齐(GFZ)是一种纤维酸类药物,对过氧化物酶体增殖物激活受体-α(PPAR-α)具有激动作用,可有效治疗高甘油三酯血症和混合性血脂异常。该药物还具有抗炎和抗氧化作用。本研究探讨了 GFZ 对 D-半乳糖(D-gal)诱导的衰老模型中肝肾功能损害的影响。我们使用了 28 只雄性小鼠,将其平均且随机分为四组:正常组、D-gal(150mg/kg/天;腹腔内 [i.p.],持续 6 周)、GFZ(100mg/kg/天 GFZ,口服 [p.o.],持续 6 周)和联合 D-gal+GFZ。通过血清肌酐、血尿素氮、丙氨酸氨基转移酶和天冬氨酸氨基转移酶来测量肝肾功能指标。通过丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶水平评估肝肾功能组织的氧化应激。最后,评估肝肾功能组织的组织病理学损伤。结果表明,D-gal 诱导的衰老导致肝肾功能指标异常。D-gal 还导致这些器官的氧化应激和组织病理学损伤显著增加。与 D-gal 处理的动物相比,GFZ 改善了功能指标和氧化应激。对肝肾功能的组织学评估也证实了这些结果。这些数据为 GFZ 在临床实践中减轻衰老引起的肝肾功能损害的潜在治疗作用提供了证据。

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