Abstract
This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI.
Highlights
This experiment is aimed to investigate whether fenofibrate administration would ameliorate the lung injury and inflammation in the model of intestinal I/R injury
Administration of fenofibrate one hour before the ischemia attenuated the severity of intestinal injury with an ameliorated sign of ischemic darkness and necrosis, the intestine still had the appearance of moderate edema. (Fig. 1A)
In terms of the apoptosis indicators, the fenofibrate treated mice were presented with significantly lesser expression level of NF-κ B p65 in the small intestine compared with the vehicle treated mice after intestinal I/R
Summary
This experiment is aimed to investigate whether fenofibrate administration would ameliorate the lung injury and inflammation in the model of intestinal I/R injury. In the histopathological examinations of the intestinal walls, the denudation of villi accompanied by severe injury was observed in the gut tissue in the vehicle group compared with the sham group (Fig. 1B). The inflammatory cytokines including TNF-α , IL-1β , IL-6, and HMGB-1 of the small intestine were significantly reduced in the fenofibrate group compared with the vehicle group (Fig. 2).
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