Electroacupuncture pretreatment ameliorates Golgi stress and the inflammation response against endotoxin-induced lung injury.

Background: Sepsis is a life-threatening condition involving organ dysfunction characterized by a generalized inflammatory syndrome, and the associated mortality rate is high. Electroacupuncture (EA) exerts benefits in endotoxemia-induced lung injury, mainly through lung inflammation reduction and cellular homeostasis, although the anti-inflammatory mechanisms underlying these benefits remain to be completely understood.

Methods: Mice were pretreated with EA or sham EA therapy 5 days prior to the induction of endotoxemia through the administration of lipopolysaccharide (LPS) and cecal ligation and puncture (CLP). Histopathological changes, systemic inflammation and cell death in the lungs were assessed. Transmission electron microscopy was employed to visually identify the structure of the Golgi complex. We examined proteins involved in maintaining the structural integrity of the Golgi apparatus and proteins associated with Golgi stress. The potential molecular mechanisms were investigated through overexpression of CREB3.

Results: EA pretreatment effectively rescued the lung from pathological changes, lung edema, cell apoptosis, and survival rate in septic mice, along with the improvement of physiological parameters. Endotoxemia strongly induces fragmented Golgi stacks, leading to fragmentation and disintegration of its shape, inducing cell apoptosis, and causing the outbreak of a large amount of inflammation in the lungs. EA therapy can significantly inhibit the fragmented process of Golgi stress to rescue the morphological changes and exert anti-inflammatory effects. And this protective effect may be related to upregulation of cAMP responsive element binding protein 3 (CREB3) and ADP-Ribosylation Factor 4 (ARF4), one of the key pathways involved in Golgi stress response. However, Sham EA (SEA) treatment did not substantially improve the fragmentation, stacking, and separation of Golgi organization, and inflammatory damage induced by endotoxin remains. This study discovered that overexpression of CREB3 may diminish the protective efficacy of EA.

Conclusion: Administering EA pretreatment at precisely selected acupoints notably improves the survival rate in mice challenged with endotoxemia and concurrently exerts a protective effect against inflammatory lung injury. This salutary impact is speculated to be mediated through the augmentation of the Golgi apparatus's stress response.