Magnesium hydride attenuates intestinal barrier injury during hemorrhage shock by regulating neutrophil extracellular trap formation via the ROS/MAPK/PAD4 pathway

Magnesium hydride (MgH 2 ) is a hydrogen storage material that is known for its high capacity and safety and is capable of releasing hydrogen in a controlled manner when administered orally. This release of hydrogen has been associated with a range of biological effects, including anti-inflammatory properties, antioxidant activity, and protection of the intestinal barrier. Previous research has shown that neutrophil extracellular traps (NETs) play a role in the dysfunction of the intestinal barrier in conditions such as sepsis and critical illnesses. However, it remains unclear as to whether MgH 2 can protect the intestinal barrier by inhibiting NET formation, and the underlying mechanisms have yet to be elucidated. A rat model of hemorrhagic shock was created, and pretreatment or posttreatment procedures with MgH 2 were performed. After 24?h, samples from the small intestine and blood were collected for analysis. In vitro, human neutrophils were incubated with either phorbol-12-myristate-13-acetate (PMA) or MgH 2 . Reactive oxygen species generation and the expression of key proteins were assessed. The results demonstrated that MgH 2 administration led to a decrease in inflammatory cytokines in the serum and mitigated distant organ dysfunction in rats with HS. Furthermore, MgH 2 treatment reversed histopathological damage in the intestines, improved intestinal permeability, and enhanced the expression of tight junction proteins (TJPs) during HS. Additionally, MgH 2 treatment was found to suppress NET formation in the intestines. In vitro pretreatment with MgH 2 alleviated intestinal monolayer barrier disruption that was induced by NETs. Mechanistically, MgH 2 pretreatment reduced ROS production and NET formation, inhibited the activation of ERK and p38, and suppressed the expression of the PAD4 protein. These findings indicated that MgH 2 may inhibit NET formation in a ROS/MAPK/PAD4-dependent manner, which reduces NET-related intestinal barrier damage, thus offering a novel protective role in preventing intestinal barrier dysfunction during HS.

文章引用产品列表