The present study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals (US National Institutes of Health, Bethesda, MD, USA). The study protocol was approved by the Committee on Ethics in Animal Experiments of Southern Medical University.
In total, 64 specific pathogen-free Sprague-Dawley rats (male or female) weighing 180–220 g were used in this study. The rats were housed in plastic cages with a controlled temperature of 25°C, humidity of 50–55%, and a 12 h light/dark cycle. All the animals had free access to food and distilled water. All rats were anesthetized and maintained with isoflurane (RWD Life Science, Shenzhen, China) and were randomly divided into six groups: the control, vehicle, resveratrol (RSV), SRT1720 (a selective activator of SIRT1), RSV+Ex527, and RSV+3-TYP groups.

In the control group, rats were anesthetized and underwent surgery without any other treatment.

In the vehicle group, the rats were given vehicle (0.3 mL) and subjected to cecal ligation and puncture (CLP) after 30 min.

In the RSV group, the rats were given RSV (0.3 mL; 50 mg/kg) and subjected to CLP after 30 min.

In the SRT1720 group, the rats were given SRT1720 (0.3 mL; 0.2 mg/kg) [16 (link)] and subjected to CLP after 30 min.

In the RSV+Ex527 group, rats were given RSV+Ex527 (0.3 mL, 50 mg/kg, and 5 mg/kg, resp.) and subjected to CLP after 30 min.

In the RSV+3-TYP group, the rats were given RSV+3-TYP (0.3 mL, 50 mg/kg, and 5 mg/kg, resp.) [15 (link)] and subjected to CLP after 30 min.

Sepsis was introduced by using the CLP technique. Specifically, midline laparotomy was performed using minimal dissection, and the cecum was ligated just below the ileocecal valve by using 4-0 silk ligatures to maintain intestinal continuity. The cecum was perforated at 2 locations 1 cm apart by using an 18-gauge needle and gently compressed until the feces were extruded. The bowel was then returned to the abdomen and the incision closed. Control rats underwent the same surgical procedures, but the cecum was neither ligated nor punctured. At the end of the operation, all rats were subcutaneously resuscitated with vehicle (normal saline, NS; 20 mL/kg). All rats were deprived of food but had free access to water after the operation. All rats received subcutaneous injections of imipenem/cilastatin (14 mg/kg) in 8 mL NS solution (40 mL/kg) at 6 h after CLP.
After the CLP model was created, 36 rats (6 in each group) were killed for tissue extraction, observation of mitochondrial morphology, and renal tubular epithelial cell (RTEC) isolation; the remaining animals (8 in each group) were used for survival analyses.
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