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

cause multiple organ injury and systemic inflammatory responses 18 . Pro-inflammatory cytokines are the contributors in the remote organ injury after intestinal I/R. Our hypothesis is based on the assumption that fenofibrate administration can decrease the expression level of inflammatory cytokines in the serum and therefore reduce distant organ injury. So we evaluated the secretion of TNF-α , IL-1β , IL-6 and ALT in the serum after intestinal I/R. Consistent with our expectation, the serum levels of these inflammatory cytokines were significantly decreased compared with the vehicle group (Table 1) . Systemic inflammatory indicators TNF-α , IL-1β , IL-6 were significantly reduced in the fenofibrate group by 68.8%, 47.5% and 65.4%, respectively, compared with the vehicle group. The blood markers of remote organ injury ALT was decreased by 29.7% in the fenofibrate group compared with the vehicle group (Table 1) . Fenofibrate alleviates ALI after intestinal I/R and abates distant organ injuries in the liver and kidney. One of the most severely damaged distant organs affected by intestinal I/R injury serves to be the lung 19 . HE staining indicated that lung tissues from vehicle-treated mice were presented with severe histological changes, including intracellular hemorrhage, alveolar congestion, exudates and infiltration of inflammatory cells, in comparison with sham groups (Fig. 3A) . However, administration with fenofibrate dramatically ameliorated these ALI histopathological alterations, as seen in the significantly reduced lung injury score ( Fig. 3B; Table 2 ). Apart from the histological indicators, we also measured biochemical variables. These variables included NO, iNOS and Iκ Bα and NF-κ B p65 of the lung tissue. The NO and iNOS of the lung tissues were significantly abated in the fenofibrate group compared with the vehicle group, implicating the protective role of fenofibrate of the ALI after intestinal I/R (Fig. 4A,B) . Besides, the lung tissue expression of NF-κ B p65 was significantly suppressed in the fenofibrate treated group and Iκ Bα was significantly elevated in the fenofibrate group in comparison with the vehicle group (Fig. 4C,D) . In order to evaluate the apoptosis in the lungs after fenofibrate treatment, we assessed the caspase-3 expression of the lung tissue. The pulmonary expression level of caspase-3 was significantly up-regulated in the vehicle group after intestinal I/R, while fenofibrate administration significantly decreased the expression level of caspase-3 compared to the vehicle groups (Fig. 4E) .