Seenak Porrnthanate, Kumphune Sarawut, Prasitsak Thanit, Nernpermpisooth Nitirut, Malakul Wachirawadee
Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, Thailand.
Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, Thailand.
Front Med (Lausanne). 2022 Nov 24;9:1039707. doi: 10.3389/fmed.2022.1039707. eCollection 2022.
Hypercholesterolemia is a major risk factor for interstitial lung disease (ILD). Atorvastatin and ezetimibe are antilipemic drugs that have pleiotropic effects. However, their effects on pulmonary fibrosis prevention and the mechanisms underlying hypercholesterolemia have not been fully investigated. This study aimed to evaluate the individual effects of atorvastatin and ezetimibe on lung inflammation and fibrosis in high-cholesterol diet (HCD)-fed rats.
Male Sprague-Dawley rats were divided into four groups - standard diet (S), standard diet + 1% cholesterol (SC), standard diet + 1% cholesterol with 30 mg/kg/day atorvastatin (SCA), and standard diet + 1% cholesterol with 10 mg/kg/day ezetimibe (SCE). At the end of an 8-week dietary schedule, serum lipid parameters and the levels of lung oxidative stress, inflammatory cytokines, and fibrotic mediators were determined.
Atorvastatin and ezetimibe treatment remarkably reduced serum lipid profiles with reversed pulmonary histological alterations, in addition to reducing the levels of lung oxidative stress, inflammation, and fibrosis in hypercholesterolemic rats.
Atorvastatin and ezetimibe treatment showed a protective effect against hypercholesterolemia-induced pulmonary fibrosis in rats. This information appears potentially useful in the prevention of PF in a hypercholesterolemia model; however, further rigorous investigations are needed to prove their clinical utility on antifibrosis.
高胆固醇血症是间质性肺疾病（ILD）的主要危险因素。阿托伐他汀和依折麦布是具有多效性的抗血脂药物。然而，它们对肺纤维化预防的作用以及高胆固醇血症的潜在机制尚未得到充分研究。本研究旨在评估阿托伐他汀和依折麦布对高胆固醇饮食（HCD）喂养大鼠肺部炎症和纤维化的个体影响。
雄性Sprague-Dawley大鼠分为四组——标准饮食（S）组、标准饮食 + 1%胆固醇（SC）组、标准饮食 + 1%胆固醇 + 30 mg/kg/天阿托伐他汀（SCA）组和标准饮食 + 1%胆固醇 + 10 mg/kg/天依折麦布（SCE）组。在8周饮食计划结束时，测定血清脂质参数以及肺氧化应激、炎性细胞因子和纤维化介质的水平。
阿托伐他汀和依折麦布治疗显著降低了血清脂质水平，逆转了肺部组织学改变，此外还降低了高胆固醇血症大鼠的肺氧化应激、炎症和纤维化水平。
阿托伐他汀和依折麦布治疗对大鼠高胆固醇血症诱导的肺纤维化具有保护作用。该信息在高胆固醇血症模型中预防肺纤维化方面似乎具有潜在用途；然而，需要进一步严格研究以证明它们在抗纤维化方面的临床效用。
