Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load

医学 败血症 阿托伐他汀 肺水肿 水肿 渗透(HVAC) 亚胺培南 免疫学 药理学 内科学 抗生素 生物 微生物学 物理 抗生素耐药性 热力学
作者
Soumen Choudhury,K Kannan,Bhojane Somnath Maruti,M. Pule Addison,Jaya Kiran Kasa,Sazad Ahmad Darzi,Thakur Uttam Singh,Subhashree Parida,Jeevan Ranjan Dash,Vishakha Singh,Santosh Kumar Mishra
出处
期刊:European Journal of Pharmacology [Elsevier]
卷期号:765: 447-456 被引量:17
标识
DOI:10.1016/j.ejphar.2015.09.009
摘要

Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1β and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice.
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