Pioglitazone and/or irbesartan ameliorate COPD-induced endothelial dysfunction in side stream cigarette smoke-exposed mice model
Pioglitazone and/or irbesartan ameliorate COPD-induced endothelial dysfunction in side stream cigarette smoke-exposed mice model
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DOI：
10.1016/j.lfs.2021.119706
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发表时间：
2021-06-14
期刊：
影响因子：
6.1
通讯作者：
Ahmed，Marwa A.
中科院分区：
文献类型：
--
作者：
Abdelhafez，Alaa T.;Gomaa，Asmaa M. S.;Ahmed，Marwa A.
吸烟是慢性阻塞性肺疾病（COPD）的主要病因.内皮功能障碍与COPD肺部疾病的严重程度有关。本研究旨在评价吡格列酮（Pio）和厄贝沙坦（Irb）单独和联合给药对COPD诱导的小鼠内皮功能障碍的有效性以及NO和H2S在其Effects.Materials和MethodsAdult雄性Swiss小鼠（n = 40，体重25-30 g）中的参与。正常对照组给予1%羧甲基纤维素（CMC）。CS组暴露于CS并给予1%CMC 3个月。CS + Pio组、CS + Irb组和CS + Pio/Irb组分别给予Pio（60 mg/kg）、Irb（50 mg/kg）及其组合，每日口服，持续3个月。观察各组大鼠体重增长、平均血压、尿白蛋白、血清NO、ET-1水平、肺组织及支气管肺泡灌洗液中TNF-α、IL-2水平。结果表明，CS诱导的小鼠COPD模型肺组织H2S、ET-1水平升高，肺组织中PPARγ蛋白表达增加，肺组织和主动脉组织中VEGF蛋白表达增加，肺组织中VEGF蛋白表达增加，肺组织中H2S、ET-1水平升高，肺组织中VEGF蛋白表达增加，肺组织中H2S、ET-1蛋白表达增加，肺组织中VEGF蛋白表达增加。Pio/Irb单独和联合给药对该疾病的病理生理学具有保护作用，联合给药组改善更多。NO和H2S以及其他测量参数之间有很强的相关性。显着性，两种药物通过其抗炎潜力和增加H2S和NO水平来实现这些效果。
AimsCigarette smoking (CS) is the main cause of chronic obstructive pulmonary disease (COPD). Endothelial dysfunction is related to the severity of pulmonary disease in COPD. This study aimed to evaluate the effectiveness of single and combined administration of pioglitazone (Pio) and irbesartan (Irb) against COPD-induced endothelial dysfunction in mice and the involvement of NO and H2S in their effects.Materials and methodsAdult male Swiss mice (n = 40, weighing 25–30 g) were assigned into 5 groups. The normal control group received 1% carboxy methyl cellulose (CMC). The CS group was exposed to CS and administered 1% CMC for 3 months. The CS + Pio, CS + Irb, and CS + Pio/Irb groups were subjected to CS and received Pio (60 mg/kg), Irb (50 mg/kg), and their combination respectively, daily orally for 3 months. Body weight gain, mean blood pressure, urinary albumin, serum NO and ET-1 levels with TNF-α and IL-2 levels in lung tissue and bronchoalveolar lavage were measured. Lung H2S and ET-1 levels, protein expression of PPARγ in lung and VEGF in lung and aortic tissues with histological changes were assessed.Key findingsOur results illustrated that CS induced a model of COPD with endothelial dysfunction in mice. Pio/Irb singly and in combination elicited protective effects against the pathophysiology of the disease with more improvement in the combined group. There is a strong correlation between NO and H2S as well as the other measured parameters.SignificanceCollectively, both drugs performed these effects via their anti-inflammatory potential and increasing H2S and NO levels.