甲氨蝶呤（MTX）是一种细胞毒性化疗和免疫抑制剂，广泛用于自身免疫性疾病和不同类型的癌症治疗。然而，其使用受到其具有致命副作用的限制，包括肾毒性和肝毒性。本研究旨在调查舍格列汀在大鼠中对甲氨蝶呤（MTX）引起的肾毒性的保护作用。24只大鼠被分为四组：对照组，接受6天的车组；MTX组，接受单剂量的MTX，然后进行五天的车辆给药；MTX+舍格列汀组，接受首次舍格列汀治疗后1小时的单剂量MTX和六天的舍格列汀；舍格列汀组，接受6天的舍格列汀。MTX和舍格列汀均以20mg/kg体重的剂量进行腹腔注射。所有大鼠都在研究的第七天被安乐死。收集肾组织和血样。评估血清血尿素氮（BUN）和肌酐水平。此外，还在肾组织中测定过氧化氢酶、谷胱甘肽过氧化物酶、超氧化物歧化酶活性和丙二醛水平。另外，进行了组织病理学分析。组织病理学评估表明MTX引起明显的肾损伤。生化分析显示MTX组血清中BUN和肌酐明显增加。此外，MTX组肾组织的氧化应激和抑制抗氧化系统明显。当单独使用时，舍格列汀不会影响这些终点，但它显著减轻了观察到的MTX引起的效应。这些结果表明，舍格列汀在大鼠中对MTX诱导的肾毒性表现出强效的抗氧化特性。

Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.