Abstract：
BACKGROUND: Experimental hepatopulmonary syndrome (HPS) is best reproduced in the rat common bile duct ligation (CBDL) model. Vildagliptin (Vild) is an anti-hyperglycemic drug that exerts beneficial anti-inflammatory, anti-oxidant and anti-fibrotic effects. Therefore, the present search aimed to explore the possible effectiveness of Vild in CBDL-induced HPS model.
METHODS: Four groups of male Wistar rats which weigh 220-270 g were used, including the normal control group, the sham control group, the CBDL group and CBDL+Vild group. The first three groups received i.p. saline, while the last group was treated with i.p. Vild (10 mg/kg/day) from the 15th to 28th day of the experiment.
RESULTS: CBDL decreased the survivability and body weight of rats, increased diameter of the pulmonary vessels, and altered the arterial blood gases and the liver function parameters. Additionally, it increased the pulmonary expressions of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) mRNA as well as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) proteins. The CBDL rats also exhibited elevation of the pulmonary interleukin-6 (IL-6), dipeptidyl peptidase-4 (DPP-4) and nitric oxide (NO) levels along with reduction of the pulmonary total anti-oxidant capacity and glucagon-like peptide-1 (GLP-1) levels. Vild mitigated these alterations and improved the histopathological abnormalities caused by CBDL.
CONCLUSIONS: Vild effectively attenuated CBDL-induced HPS through its anti-oxidant and anti-inflammatory effects along with its modulatory effects on ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling implicated in the regulation of intrapulmonary vasodilatation and angiogenesis, respectively.
METHODS: Four groups of male Wistar rats which weigh 220-270 g were used, including the normal control group, the sham control group, the CBDL group and CBDL+Vild group. The first three groups received i.p. saline, while the last group was treated with i.p. Vild (10 mg/kg/day) from the 15th to 28th day of the experiment.
RESULTS: CBDL decreased the survivability and body weight of rats, increased diameter of the pulmonary vessels, and altered the arterial blood gases and the liver function parameters. Additionally, it increased the pulmonary expressions of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) mRNA as well as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) proteins. The CBDL rats also exhibited elevation of the pulmonary interleukin-6 (IL-6), dipeptidyl peptidase-4 (DPP-4) and nitric oxide (NO) levels along with reduction of the pulmonary total anti-oxidant capacity and glucagon-like peptide-1 (GLP-1) levels. Vild mitigated these alterations and improved the histopathological abnormalities caused by CBDL.
CONCLUSIONS: Vild effectively attenuated CBDL-induced HPS through its anti-oxidant and anti-inflammatory effects along with its modulatory effects on ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling implicated in the regulation of intrapulmonary vasodilatation and angiogenesis, respectively.
摘要：
背景：实验性肝肺综合征（HPS）最好在大鼠胆总管结扎（CBDL）模型中再现。维格列汀（Vild）是一种抗高血糖药物，具有有益的抗炎作用，抗氧化和抗纤维化作用。因此,本研究旨在探索Vild在CBDL诱导的HPS模型中的可能有效性。
方法：使用四组体重为220-270克的雄性Wistar大鼠，包括正常对照组,假对照组，CBDL组和CBDL+Vild组。前三组接受腹腔注射生理盐水，而最后一组在实验的第15天至第28天用i.p.Vild（10mg/kg/天）治疗。
结果：CBDL降低了大鼠的生存能力和体重，肺血管直径增加，改变动脉血气和肝功能参数。此外,它增加了内皮素-1（ET-1）和肿瘤坏死因子-α（TNF-α）mRNA以及内皮型一氧化氮合酶（eNOS）的表达，诱导型一氧化氮合酶（iNOS）和血管内皮生长因子-A（VEGF-A）蛋白。CBDL大鼠还表现出肺白细胞介素-6（IL-6）的升高，二肽基肽酶-4（DPP-4）和一氧化氮（NO）水平以及肺总抗氧化能力和胰高血糖素样肽-1（GLP-1）水平的降低。Vild减轻了这些改变，并改善了CBDL引起的组织病理学异常。
结论：Vild通过其抗氧化和抗炎作用以及对ET-1/NOS/NO和TNF-α/IL-6/VEGF-A信号传导的调节作用，有效地减弱了CBDL诱导的HPS，分别。
方法：使用四组体重为220-270克的雄性Wistar大鼠，包括正常对照组,假对照组，CBDL组和CBDL+Vild组。前三组接受腹腔注射生理盐水，而最后一组在实验的第15天至第28天用i.p.Vild（10mg/kg/天）治疗。
结果：CBDL降低了大鼠的生存能力和体重，肺血管直径增加，改变动脉血气和肝功能参数。此外,它增加了内皮素-1（ET-1）和肿瘤坏死因子-α（TNF-α）mRNA以及内皮型一氧化氮合酶（eNOS）的表达，诱导型一氧化氮合酶（iNOS）和血管内皮生长因子-A（VEGF-A）蛋白。CBDL大鼠还表现出肺白细胞介素-6（IL-6）的升高，二肽基肽酶-4（DPP-4）和一氧化氮（NO）水平以及肺总抗氧化能力和胰高血糖素样肽-1（GLP-1）水平的降低。Vild减轻了这些改变，并改善了CBDL引起的组织病理学异常。
结论：Vild通过其抗氧化和抗炎作用以及对ET-1/NOS/NO和TNF-α/IL-6/VEGF-A信号传导的调节作用，有效地减弱了CBDL诱导的HPS，分别。
