Combination therapy with hypertonic saline and ulinastatin attenuates intestinal and kidney injury induced by trauma-hemorrhagic shock in rats

Trauma-hemorrhagic shock (HS) often leads to remote organ injury, particularly the gut and kidney. While fluid resuscitation is essential, optimal strategies to mitigate organ damage remain lacking. This study investigated the combined effects of hypertonic saline (HTS) and ulinastatin (UTI) on HS-induced intestinal and renal injuries. Male Sprague-Dawley rats were randomized into five groups: Sham, HS, HS+HTS, HS+UTI, and HS+HTS-UTI. A standardized HS model was used. Interventions were administered during resuscitation. Hemodynamics were monitored. At 24 h post-resuscitation, serum and tissues (ileum, kidney) were collected. Intestinal and renal injuries were assessed via histopathology, apoptosis (TUNEL), inflammation (ELISA for TNF-α, IL-6), oxidative stress (MDA, SOD), barrier function (FITC-dextran, tight junction proteins ZO-1/Occludin), and renal function/injury markers (creatinine, BUN, KIM-1, NGAL). HS induced severe hypotension, electrolyte disturbance, systemic inflammation, oxidative stress, and histopathological damage in the intestine and kidney, along with increased intestinal permeability, apoptosis, and renal dysfunction. Monotherapy with either HTS or UTI provided partial protection. However, the combination therapy demonstrated superior protective effects, which were significantly greater than either monotherapy alone. The HTS and UTI combination most effectively restored mean arterial pressure, suppressed systemic and tissue inflammation/oxidative stress, preserved intestinal morphology and barrier integrity, reduced intestinal and renal apoptosis, and ameliorated renal histology and function while downregulating KIM-1 and NGAL expression. The mechanism involves simultaneous mitigation of inflammation, oxidative stress, and apoptosis, along with preservation of intestinal barrier and renal tubular integrity.