Effects of astragaloside IV on lung injury and inflammation after hemorrhagic shock and resuscitation in rats

Abstract

Objective To investigate the effects of astragaloside Ⅳ on lung injury and inflammation after hemorrhagic shock and resuscitation in rats. Methods Twenty-four male Sprague Dawley rats were randomly divided in 3 groups, including Sham group, hemorrhagic shock-resuscitation group (HS-R group) and astragaloside Ⅳ+ hemorrhagic shock-resuscitation group (AGS+ HS-R group). Hemorrhagic shock was induced by blood drawing from the femoral artery, and the resuscitation was performed by infusion of shed blood and two-fold volume saline. The operations for Sham group were the same with HS-R group, except that the blood drawing and fluid resuscitation were not performed. The rats in AGS+ HS-R group were subjected to hemorrhagic shock, and 20 mg/kg of astragaloside Ⅳ was intraperitoneally injected at the onset of resuscitation. Two h after resuscitation, histological changes were observed under light microscope, and myeloperoxidase (MPO) activities were determined with a commercial kit. The protein levels of cytoplasmic high mobility group protein B1 (HMGB1) as well as Toll-like receptor 4 (TLR4) and phospho-p38 mitogen activated protein kinase (p-p38MAPK) protein expression levels were detected by Western blotting. The protein levels of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β were examined by enzyme linked immunosorbent assay (ELISA). Results Histological results showed that the lung injury after hemorrhagic shock and resuscitation was attenuated by the treatment of astragaloside Ⅳ. As compared with HS-R group [(8.2±1.6) U/g], the treatment of astragaloside Ⅳ [(5.2±0.9) U/g] decreased MPO activities by 36.6% (P<0.01). In addition, the astragaloside Ⅳ treatment also down-regulated the expression levels of cytoplasmic HMGB1 as well as TLR4 and p-p38MAPK by 24.9%, 27.5%, and 23.7%, respectively (P<0.01 or P<0.05). The results of ELISA suggested that the lung protein levels of TNF-α, and IL-1β after hemorrhagic shock and resuscitation were decreased by 66.3%, and 44.3% respectively (P<0.01). Conclusion Astragaloside Ⅳ might attenuate the lung injury after hemorrhagic shock and resuscitation via inhibition of HMGB1/TLR4 signaling. Key words: Astragaloside Ⅳ; Hemorrhagic shock; Lung injury; Inflammatory response