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

Mice model and drug treatment in mice. Eighteen mice were randomly assigned into three groups (n = 6/group):sham, intestinal I/R + DMSO, and I/R + fenofibrate. Fenofibrate (Abcam, Beijing, China) was suspended with dimethyl sulphoxide (DMSO) solution to the final concentration of 10 mg/ml. The fenofibrate (100 mg/kg of body weight) or equivalent volume of DMSO (vehicle) was intraperitoneally injected into the mice 60 minutes before the ischemia. With respect to the intestinal I/R model, mice were anesthetized with sodium pentobarbital (50 mg/kg, i.p.), allowed to breathe spontaneously during the surgery. After anesthetization, the abdominal wall was opened by midline incision. The superior mesenteric artery was exposed and clamped by an aneurysm clip in order to achieve the intestinal ischemia state when the pulselessness of the mesentery and paleness of the small bowel appeared. On completion of 60 minutes of ischemia, the clip was removed to reperfuse the intestine for 60 minutes. The return of the pulses, the reestablishment of the pink color, and the enhanced intestinal peristalsis were assumed to sign the reperfusion of the intestine. Sham group underwent the identical operation protocols except for the clamping of superior mesenteric artery. The ischemia/reperfusion time was set up according to our experience in our pilot study. All mice were performed a fluid resuscitation with intraperitoneally injection of 1.0 ml of normal saline just after surgery. The mice were sacrificed after completion of intestinal I/R and tissues were quickly harvested. Blood samples were collected by cardiac puncture and centrifuged at 3000 g for 10 minutes in order to collect serum. Tissue and serum were snap frozen in liquid nitrogen and stored at − 80 °C until analysis. Additional experiments for observation of survival over the course of 24 hours were performed (n = 15/groups). In the survival experiment, a single dose of 100 mg/kg of fenofibrate or equal volume of DMSO (vehicle) was injected intraperitoneally one hour before the ischemia.