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Ginsenoside ameliorated ventilator-induced lung injury in rats.

ABSTRACT:

Background

Ginsenosides have antioxidant and anti-inflammatory features. This study aimed to evaluate the biologic effects of ginsenoside Rb2 pretreatment on ventilator-induced lung injury (VILI) in rats.

Methods

Rats were divided into four groups with 12 rats per group: control; low tidal volume (TV), TV of 6 mL/kg, VILI, TV of 20 mL/kg, positive end-expiratory pressure of 5 cm H₂O, and respiratory rate of 60 breaths per minute for 3 h at an inspiratory oxygen fraction of 0.21; and ginsenosides, treated the same as the VILI group but with 20 mg/kg intraperitoneal ginsenoside pretreatment. Morphology was observed with a microscope to confirm the VILI model. Wet-to-dry weight ratios, protein concentrations, and pro-inflammatory cytokines in the bronchoalveolar lavage fluid were measured. RNA sequencing of the lung tissues was conducted to analyze gene expression.

Results

High TV histologically induced VILI with alveolar edema and infiltration of inflammatory cells. Ginsenosides pretreatment significantly reduced the histologic lung injury score compared to the VILI group. Wet-to-dry weight ratios, malondialdehyde, and TNF-α in bronchoalveolar lavage fluid were significantly higher in the VILI group and ginsenoside pretreatment mitigated these effects. In the immunohistochemistry assay, ginsenoside pretreatment attenuated the TNF-α upregulation induced by VILI. We identified 823 genes differentially presented in the VILI group compared to the control group. Of the 823 genes, only 13 genes (Arrdc2, Cygb, Exnef, Lcn2, Mroh7, Nsf, Rexo2, Srp9, Tead3, Ephb6, Mvd, Sytl4, and Ube2l6) recovered to control levels in the ginsenoside group.

Conclusions

Ginsenosides inhibited the inflammatory and oxidative stress response in VILI. Further studies are required on the 13 genes, including LCN2.

SUBMITTER: Cho WH

PROVIDER: S-EPMC7682776 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Respiratory distress syndrome is responsible for 40 to 60 percent mortality. An over mortality of about 10 percent could result from additional lung injury and inflammation due to the life-support mechanical ventilation, which stretches the lung. It has been recently demonstrated, in vitro, that pharmacological activation of the alpha 7 nicotinic receptors (α7-nAChR) could down regulate intracellular mediators involved in lung cell inflammatory response to stretch. Our aim was to test in vivo the protective effect of the pharmacological activation of the α7-nAChR against ventilator-induced lung injury (VILI). Anesthetized rats were ventilated for two hours with a high stretch ventilation mode delivering a stroke volume large enough to generate 25-cmH(2)O airway pressure, and randomly assigned to four groups: pretreated with parenteral injection of saline or specific agonist of the α7-nAChR (PNU-282987), or submitted to bilateral vagus nerve electrostimulation while pre-treated or not with the α7-nAChR antagonist methyllycaconitine (MLA). Controls ventilated with a conventional stroke volume of 10 mL/kg gave reference data. Physiological indices (compliance of the respiratory system, lung weight, blood oxygenation, arterial blood pressure) and lung contents of inflammatory mediators (IL-6 measured by ELISA, substance P assessed using HPLC) were severely impaired after two hours of high stretch ventilation (sham group). Vagal stimulation was able to maintain the respiratory parameters close to those obtained in Controls and reduced lung inflammation except when associated to nicotinic receptor blockade (MLA), suggesting the involvement of α7-nAChR in vagally-mediated protection against VILI. Pharmacological pre-treatment with PNU-282987 strongly decreased lung injury and lung IL-6 and substance P contents, and nearly abolished the increase in plasmatic IL-6 levels. Pathological examination of the lungs confirmed the physiological differences observed between the groups. In conclusion, these data suggest that the stimulation of α7-nAChR is able to attenuate VILI in rats.