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阿托伐他汀与胺碘酮联合使用会增加大鼠发生肺纤维化的风险。

Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats.

作者信息

Nasri Hamid-Reza, Joukar Siyavash, Kheradmand Hamid, Poursalehi Hamid-Reza, Dabiri Shahriar

机构信息

Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Med Princ Pract. 2016;25(2):150-4. doi: 10.1159/000442202. Epub 2015 Nov 6.

DOI:10.1159/000442202
PMID:26544718
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5588350/
Abstract

OBJECTIVE

The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats.

MATERIALS AND METHODS

Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 weeks. The amiodarone group (AMI) received 2 intratracheal instillations of amiodarone (6.25 mg/kg in 0.3 ml of water) on days 0 and 2 and 0.5 ml of distilled water (like the CTL). The amiodarone plus atorvastatin group (AMI + AT) received both these drugs (same doses and methods as for the AMI and AT). After 28 days, the rate of lung fibrosis was estimated according to pathological criteria of lung sections and measurements of hydroxyproline in pieces of left lung tissue.

RESULTS

The lung hydroxyproline content was higher in the treated groups (CTL: 0.35 ± 0.017, AT: 0.38 ± 0.012, AMI: 0.375 ± 0.018 and AMI + AT: 0.38 ± 0.012 unit/mg protein), but did not reach significance when compared with the CTL (p = 0.56). Amiodarone administration significantly increased the score of pulmonary fibrosis (0.5) in comparison with the AT (0.125) and CTL (0) (p < 0.5). The combination of amiodarone and atorvastatin exacerbated the pulmonary fibrosis (1.5; p < 0.01) compared to the AMI (0.5; p < 0.001), AT (0.125) and CTL (0).

CONCLUSION

In this study, the concomitant administration of amiodarone and atorvastatin increased pulmonary fibrosis in rats.

摘要

目的

本研究旨在评估阿托伐他汀给药对胺碘酮诱导的大鼠肺纤维化的影响。

材料与方法

36只雄性Wistar大鼠随机分为4组。对照组(CTL)接受蒸馏水(第0天和第2天经气管内给予0.3 ml,从第0天开始口服0.5 ml,持续3周)。阿托伐他汀组(AT)除经气管内给予蒸馏水外,从第0天开始口服1 mg/kg阿托伐他汀,持续3周。胺碘酮组(AMI)在第0天和第2天经气管内滴注2次胺碘酮(6.25 mg/kg溶于0.3 ml水中),并给予0.5 ml蒸馏水(与CTL相同)。胺碘酮加阿托伐他汀组(AMI + AT)接受这两种药物(剂量和方法与AMI和AT相同)。28天后,根据肺切片的病理标准和左肺组织块中羟脯氨酸的测量值评估肺纤维化程度。

结果

各治疗组肺羟脯氨酸含量均较高(CTL:0.35±0.017,AT:0.38±0.012,AMI:0.375±0.018,AMI + AT:0.38±0.012单位/毫克蛋白),但与CTL相比无显著差异(p = 0.56)。与AT组(0.125)和CTL组(0)相比,胺碘酮给药显著增加了肺纤维化评分(0.5)(p < 0.5)。与AMI组(0.5;p < 0.001)、AT组(0.125)和CTL组(0)相比,胺碘酮与阿托伐他汀联合使用加剧了肺纤维化(1.5;p < 0.01)。

结论

在本研究中,胺碘酮与阿托伐他汀联合给药增加了大鼠的肺纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa4/5588350/1bf1a2c5f46a/mpp-0025-0150-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa4/5588350/1bf1a2c5f46a/mpp-0025-0150-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa4/5588350/1bf1a2c5f46a/mpp-0025-0150-g01.jpg

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