Lung injury is a serious condition encountered following hepatic ischemia/reperfusion (IR). This study aimed to explore whether a dipeptidyl peptidase-4 inhibitor agent vildagliptin (V) could alleviate the lung injury caused by hepatic IR in a rat model and if so elucidate its molecular protective mechanism. Three groups of rats were used. Sham group: received normal saline and exposed to a sham operation, IR group: received normal saline and subjected to the operation of hepatic I (45 min)/ R (180 min), V+IR group: received for 10 days intraperitoneal injection of V (10 mg/kg/day). After reperfusion, liver and lung were collected for biochemical and histological evaluation. Hepatic IR exhibited significant elevation in serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) enzyme levels, serum and lung malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) in addition to lung nitric oxide (NO) levels, hypoxia-inducible factor 1-alpha (HIF-1α) mRNA and protein levels, hepatocyte growth factor (HGF) mRNA expression, and inducible nitric oxide synthase (iNOS) mRNA and protein expressions in lung tissue along with a marked reduction in the serum and lung content of catalase in comparison to the sham group. Moreover, liver and lung injury in the IR group was detected by histopathological examination. Vildagliptin ameliorated markedly the biochemical changes as well as liver and lung architecture in comparison to the IR group. Vildagliptin mitigated the induced lung injury by hepatic IR via suppression of oxidative stress markers, pro-inflammatory cytokine TNF-α as well as the HIF1-α/iNOS/HGF expressions in lung tissue.

肺损伤是肝缺血/再灌注（IR）后遇到的严重病症。本研究旨在探讨二肽基肽酶4抑制剂维格列汀（V）是否可以减轻大鼠模型中肝IR引起的肺损伤，并阐明其分子保护机制。使用三组大鼠。假手术组：给予生理盐水并进行假手术，IR组：给予生理盐水并进行肝I（45分钟）/R（180分钟）操作，V+IR组：腹腔注射10天V（10 毫克/公斤/天）。再灌注后，收集肝脏和肺进行生化和组织学评估。肝脏 IR 表现出血清丙氨酸氨基转移酶 (ALT)、碱性磷酸酶 (ALP) 和乳酸脱氢酶 (LDH) 酶水平、血清和肺丙二醛 (MDA) 以及肿瘤坏死因子-α (TNF-α) 和肺的显着升高肺组织中一氧化氮 (NO) 水平、缺氧诱导因子 1-α (HIF-1α) mRNA 和蛋白水平、肝细胞生长因子 (HGF) mRNA 表达、诱导型一氧化氮合酶 (iNOS) mRNA 和蛋白表达与假手术组相比，血清和肺中过氧化氢酶的含量显着降低。此外，组织病理学检查发现IR组有肝、肺损伤。与IR组相比，维格列汀显着改善了生化变化以及肝脏和肺结构。维格列汀通过抑制肺组织中氧化应激标志物、促炎细胞因子 TNF-α 以及 HIF1-α/iNOS/HGF 的表达来减轻肝 IR 引起的肺损伤。