Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice

Zhu, Qiankun; He, Guizhen; Wang, Jie; Wang, Yukang; Chen, Wei

ALI is a commonly seen clinical syndrome of respiratory failure. The pathophysiology mechanism of ALI induced by intestinal I/R remains to be complicated. But it is now widely acknowledged that the ALI is the result of an integrated network of inflammatory mediators and many inflammatory cells 22 . The proinflammatory mediators exert a vital role in the onset of ALI. With regard to the ALI with the etiology of I/R, it has been suggested that occlusion of the super-mesenteric artery causes local intestinal injury and the reperfusion process activates a series of systemic inflammatory responses, which can further damage multiple organs, including the lung, through blood circulations 23, 24 . In the ALI, the alveolar exudates, bleeding and neutrophils are accumulated in the lung tissue. TNF-α , IL-1β and IL-6 activity is often used to assess the extent of inflammation in intestinal I/R, and there is ample evidence that TNF-α , IL-1β and IL-6 are pivotal inflammatory mediators in the intestinal I/R-caused ALI 25 . In this study, we found that after the administration of fenofibrate the TNF-α , IL-1β and IL-6 activity was significantly decreased in both the intestine and the lung tissue after intestinal I/R. Injured lung epithelium and endothelium also contributes to the development of ALI 26, 27 , and one feature of this process is the loss of cells through apoptosis. Apoptosis is the major event by which cell death occurs in intestinal I/R mice epithelium and endothelium 28 . To confirm the hypothesis that fenofibrate is involved in regulating apoptosis in the model of intestinal I/R, the caspase-3 activity was used as an apoptotic index to evaluate the degree of apoptosis in the lung tissue. In our experiment, the caspase-3 was significantly reduced in the lung tissue after the fenofibrate treatment. Therefore, we could to some extent state that fenofibrate attenuated I/R-caused ALI in part by apoptosis.