Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis

BACKGROUND: Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available. AIM: To explore the effect and mechanism of HPA inhibition in S-AGI patients. METHODS: In our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1(st), 3(rd) and 7(th) d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI. RESULTS: Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group (P < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased (P < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased (P < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups (P > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI. CONCLUSION: HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.