Inflammation and Edema in the Lung and Kidney of Hemorrhagic Shock Rats Are Alleviated by Biliary Tract External Drainage via the Heme Oxygenase-1 Pathway

Abstract

The lung and kidney are two organs that are easily affected by hemorrhagic shock (HS). We investigated roles of biliary tract external drainage (BTED) in inflammation and edema of the lung and kidney in HS and its relationship with the heme oxygenase-1 (HO-1) pathway. Rat models of HS were induced by drawing blood from the femoral artery until a mean arterial pressure (MAP) of 40 ± 5 mmHg was achieved. A MAP of 40 ± 5 mmHg was maintained for 60 min. Thirty-six Sprague-Dawley rats were randomized to the following groups: sham group; HS group; HS + zinc protoporphyrin IX (ZnPP), a specific HO-1 inhibitor, group; HS + BTED group; HS + BTED + ZnPP group; and HS + BTED + bile infusion (BI) group. HO-1 levels, aquaporin-1 levels, and ratios of dry/wet in the lung and kidney increased markedly after BTED, but tumor necrosis factor-α and myeloperoxidase levels in the lung and kidney decreased significantly after BTED under HS conditions. Under the condition that HO-1 was inhibited by ZnPP, all these effects induced by BTED disappeared in the lung and kidney. These results demonstrated that inflammation and edema of the lung and kidney of HS rats are alleviated by BTED via the HO-1 pathway.

Hemin Attenuated LPS-Induced Acute Lung Injury in Mice via Protecting Pulmonary Epithelial Barrier and Regulating Ho-1/Nlrp3-Mediated Pyroptosis

“…In the occurrence of ALI, the edema fluid is serious exudation, mainly containing water and plasma protein. In previous studies, HO-1 activation decreased the water content of lung tissues in ALI, suggesting an inhibitory role of HO-1 in edema development (19). The present study revealed that hemin preserved the ability of alveolar epithelia to initiate the vectorial fluid transport after LPS exposure.…”

Protection against monocrotaline-induced pulmonary arterial hypertension and caveolin-1 downregulation by fluvastatin in rats

“…The right lower lobe of the lung was subsequently isolated, placed in liquid nitrogen and stored at -80˚C until use in western blot analysis. The presence of pulmonary edema was evaluated by measuring the ratio of dry/wet lung weight as described previously (13).…”

Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications

“…Edema, endothelial and epithelial damage followed by a release of cytokines and chemokines, activation, recruitment and extravasation of leukocytes are the characteristics features of ventilator-induced lung injury (VILI) [ 96 ]. There has been extensive evidence to support a protective role of HO-1 activation in VILI by decreased pro-inflammatory cytokine expression including TNF-α, IL-8, decreased neutrophil, etc., and increased expression of anti-inflammatory cytokines like IL-10 [ 97 , 98 ].…”