Hydrogen sulfide (H₂S) ameliorates sepsis-induced brain injury by upregulating heme oxygenase-1 (HO-1) to inhibit high-mobility group box 1 (HMGB1) release

Abstract

The incidence of brain injury in sepsis patients has been as high as 70 %, which has been a significant cause of septic patients' death. However, the pathophysiology of brain injury in sepsis is multifactorial and inconclusive. There are no clear reasons or effective treatments for brain injury induced by sepsis. The experiment aims to research how Hydrogen sulfide (H₂S) affects sepsis-induced brain injury. Male ICR mice developed sepsis via cecal ligation and puncture (CLP). Isodose H₂S was administered before operation and at 1、12 h post-operation. Zinc protoporphyrin IX (ZnPPIX, a HO-1 inhibitor) was intraperitoneally injected 1 h before surgery. After an operation, the survival rate of 7 days was observed and recorded. Morris water maze and Y-maze were applied to evaluate cognitive function. The expression level of Bad and Bcl-2 and neuronal apoptosis by TUNEL assay in the hippocampus were assessed. We used different methods to measure the protein expression and mRNA levels of heme oxygenase-1(HO-1), high-mobility group box 1 (HMGB1) and the activity of HO-1 in hippocampus neurons. The rate of survivors and cognitive impairment of septic mice were markedly improved after H₂S treatment, and the brain injury in septic mice such as pathological damage and the expression change of Bad and Bcl-2 significantly alleviated. We discovered that the useful effects of H₂S on brain injury in septic mice were related to the decreased level of HMGB1 in the hippocampus. In addition, H₂S treatment alleviated brain injury of septic mice by promoting the expression and activity of HO-1. Moderate exogenous H₂S treatment would be a potential treatment to relieve sepsis brain injury.