Background Delayed fluid resuscitation following severe burns significantly exacerbates intestinal ischemia-reperfusion injury, thereby impairing intestinal barrier function. However, the specific protective mechanism of peroxisome proliferator-activated receptor γ (PPAR-γ) on the intestinal barrier in this particular pathological context has not been systematically reported.

Objective To investigate the expression characteristics of PPAR-γ and its role in intestinal barrier injury following severe burns with delayed fluid resuscitation.

Methods The study consisted of two parts. The first part was a time-dependent experiment involving 30 C57/BL mice subjected to a 30% total body surface area scald model. Animals were randomly divided into five groups: sham-operated (Sham), immediate fluid resuscitation (PR), delayed resuscitation at 3 hours (3hR), delayed resuscitation at 6 hours (6hR), and no resuscitation (NR). At 12 hours post-injury, intestinal pathological damage, intestinal barrier permeability markers serum intestinal-type fatty acid-binding protein (iFABP) and serum D-amino acid oxidase (DAO), expression of tight junction proteins zonula occludens-1 (ZO-1), Occludin, and PPAR-γ expression were assessed. The second part was an intervention experiment involving 18 mice divided into three groups: delayed 6-hour resuscitation (6hR), delayed 6-hour resuscitation with rosiglitazone (6hRR), and delayed 6-hour resuscitation with GW9662 (6hGR). In addition to evaluating the aforementioned parameters, inflammatory cytokine levels (TNF-α) and Interleukin-1 beta (IL-1β) were measured.

Results Compared to the PR group, all delayed resuscitation groups (3hR, 6hR, and NR) exhibited significantly aggravated intestinal injury at 12 hours post-injury, as evidenced by significantly increased histopathological scores (P < 0.01), elevated serum intestinal permeability markers iFABP and DAO (P < 0.01), reduced expression of tight junction proteins ZO-1 and Occludin (P < 0.01, P < 0.05), and significantly downregulated PPAR-γ expression (6hR and NR groups, P < 0.01). Compared to the 3hR group, more severe delayed resuscitation groups showed progressively worsened intestinal injury. At 12 hours post-injury, the 6hR and NR groups displayed significantly deteriorated histopathological scores (P < 0.01), serum DAO levels (P < 0.05), and expression of ZO-1 and Occludin. Compared to the 6hR group, the 6hRR group exhibited significantly upregulated PPAR-γ expression (P < 0.01, P < 0.05), accompanied by markedly improved intestinal pathological damage (P < 0.01), reduced serum iFABPand DAO levels (P < 0.01), enhanced ZO-1 and Occludin expression (P < 0.01, P < 0.05), and suppressed TNF-α and IL-1β levels (P < 0.01). Conversely, compared to the 6hRR group, the 6hGR group showed opposite effects, with downregulated PPAR-γ expression, aggravated histopathological damage (P < 0.01), increased serum iFABP and DAO levels (P < 0.01), reduced ZO-1 and Occludin expression (P < 0.01), and elevated TNF-α and IL-1β levels (P < 0.01).

Conclusion PPAR-γ alleviates delayed fluid resuscitation-induced intestinal barrier injury by suppressing inflammatory responses and maintaining the stability of tight junction proteins. Early fluid resuscitation or pharmacological activation of PPAR-γ holds potential therapeutic value and provides a novel target for optimizing burn resuscitation strategies.