Rhabdomyolysis (RM) is the destruction and disintegration of striated muscle which may be caused by several factors such as compression, exercise, high fever, drugs, and inflammation. Rhabdomyolysis leads to the entry of muscle cell components (such as creatine kinase and myoglobin) into the extracellular fluid and blood circulation, leading to a series of pathological changes such as electrolyte and acid-base balance disorders, coagulation dysfunction, and multi-organ dysfunction [1].

Multi-organ injury is a common sequela of rhabdomyolysis and is associated with high mortality and disability rates. In a retrospective study of 2371 patients with rhabdomyolysis, 19% of patients had poor prognosis (8.0% required renal replacement therapy [RRT]; 14.1% died during hospitalization), and the most common factors contributing to poor outcomes were cardiac arrest (58.5%), sepsis (39.3%), and osteo-fascial compartment syndrome (41.2%) [2]. In the aftermath of the 2008 earthquake in China, 28% of rhabdomyolysis patients with crush injuries who received treatment in frontline ICUs had acute kidney failure, 19% had acute heart failure, 12.5% developed multi-organ dysfunction syndrome, and all died [3].

Acute kidney injury (AKI) is the most common tissue injury caused by rhabdomyolysis and is mainly characterized by myoglobinemia, myoglobinuria, and acute tubular necrosis [4]. The research on rhabdomyolysis is also mainly focused on acute kidney injury, while there is a paucity of research on heart and lung, the core organs of pre hospital emergency treatment. Rhabdomyolysis has been shown to lead to arrhythmia, abnormal electrocardiogram, and apoptosis of myocardial cells [5,6]. The lung may show interstitial edema and hemorrhage [[7], [8], [9]]. The injury of heart, lung, and other vital organs is an important cause of death and disability caused by rhabdomyolysis. However, there is a lack of systematic research on the characteristics of rhabdomyolysis-induced injury in various organs and the underlying pathogenetic mechanisms, and especially the interaction between organs. This has constrained the development of completely effective countermeasures. The current treatment of rhabdomyolysis-induced multi-organ dysfunction is mainly symptomatic and supportive treatment, including fluid and electrolyte hemostasis and RRT. Elucidating the characteristics and mechanism of rhabdomyolysis-induced multi-organ dysfunction may help identify early biomarkers of injury and unravel novel therapeutic targets.

The most common method used to construct rhabdomyolysis models is intramuscular injection of glycerol. Glycerin is a hypertonic solution, which can lead to the destruction of muscle, and the myoglobin in the muscle cell enters the blood, causing rhabdomyolysis [10]. Therefore, in this study, we established a rat model of rhabdomyolysis by intramuscular injection of glycerol [11]. Twenty-four hours after successful modeling, the pathological changes in kidneys, hearts, lungs, and other organs were identified through histopathological, biochemical, and molecular biological tests. The core mechanism of rhabdomyolysis-induced multi-organ damage was explored through proteomic analysis. Our findings may lay the foundation for identification of early biomarkers of injury and novel therapeutic targets.