Ppif Gene Knockout Alleviates Pancreatic Injury in Mice With Cecal Ligation and Puncture-induced Sepsis.

INTRODUCTION

The peptidyl-propyl cis-trans isomerase F (Ppif) gene encodes cyclophilin D. Its involvement suggests that sepsis-induced pancreatic injury may relate to mitochondrial membrane pore transition proteins, offering potential targets for pancreatic functional protection. This study aimed to determine whether sepsis leads to pancreatic injury and whether knockout (KO) of Ppif protects against sepsis-induced pancreatic injury.

METHODS

A septic mouse model was established using cecal ligation and puncture (CLP). Mice were divided into four groups: sham, CLP, Ppif KO-sham, and Ppif KO-CLP. Serum amylase and interleukin (IL)-6 levels were measured in blood and pancreatic tissues 24 h post CLP. Pancreatic tissues were analyzed using hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and electron microscopy.

RESULTS

In the CLP-induced sepsis model mice, serum IL-6, serum amylase, pancreatic tissue pathological scores, and terminal deoxynucleotidyl transferase dUTP nick-end labeling apoptosis indices were elevated. Compared with wild-type CLP mice, Ppif KO mice exhibited lower levels of serum IL-6 and amylase, pancreatic tissue pathological scores, and apoptosis indices, indicating that KO of Ppif had a protective effect against septic pancreatic injury. Electron microscopy of tissues from CLP mice revealed basement membrane irregularities, nuclear shrinkage, mitochondrial swelling, cristae deformation, and endoplasmic reticulum structural disorder. In Ppif KO CLP mice, pancreatic acinar cells exhibited more autophagosomes.

CONCLUSIONS

Our study demonstrates that fecal peritonitis triggers a systemic inflammatory response, which subsequently induces pancreatic injury, and that KO of Ppif may mitigate this pathological injury.