RESUMO
Among the multiple organ injuries induced by sepsis, acute lung injury (ALI) triggered by an excessive inflammatory response is one of the main causes contributing to patient death, and inhibition of the inflammation cascade is the key therapeutic strategy to improve prognosis. The NLRP3 inflammasome complex is considered an intracellular signaling molecule closely associated with the uncontrolled inflammatory response in sepsis-induced ALI. Therefore, exploring new targets to repress its activation is regarded as a potential therapeutic strategy. Growing evidence demonstrated that heme oxygenase-1 (HO-1) contributed to general anti-inflammation and exerted a protective role in ALI, but its underlying mechanisms have not been clarified completely. Herein, we investigated HO-1 was elevated in alveolar macrophages isolated from bronchoalveolar lavage fluid (BALF) of sepsis mice. HO-1 abundance suppressed NLRP3 inflammasome complex activation and attenuated pro-inflammatory cytokines release, thereby alleviating sepsis-induced ALI. Whereas inhibition of HO-1 reached the opposite effect. Meanwhile, HO-1 is an effective and functionally relevant regulator of autophagic flux. HO-1 activator decreased the expression of P62 and enhanced the LC3 II/LC3 I ratio, resulting in autophagic flux activation. In addition, the protective effects HO-1 exerted in sepsis-induced ALI could be abolished by autophagic flux inhibitor. Autophagic flux activator could suppress NLRP3 inflammasome activation and attenuate ALI, while autophagic flux inhibitor had the opposite effect. In conclusion, our study revealed increased HO-1 expression inhibited the level of NLRP3 inflammasome via regulating the activation of autophagic flux, thus attenuating inflammatory response and alleviating sepsis-induced ALI.
RESUMO
Acute myocardial infarction with cardiogenic shock (AMI-CS) refers to the rapid decrease in cardiac output in a short period of time, and it leads to severe insufficient perfusion of various organs and causes systemic microcirculatory dysfunction, which is the most common cause of the death of patients with acute myocardial infarction (AMI). At present, the main strategy for clinical treatment of AMI-CS is revascularization, which reduces the mortality of AMI-CS. However, myocardial ischemia and reperfusion can cause ischemia/reperfusion (I/R) injury, induce myocardial mitochondrial dysfunction, and a large amount of reactive oxygen species (ROS) accumulation. Mitochondrial-mediated apoptosis of cardiomyocytes is the main reason of cardiomyocyte death during reperfusion injury. This article summarizes the role of mitochondrial in AMI-CS, which focus on three aspects of mitochondrial permeability transition pore (mPTP) opening, mitochondrial autophagy and mitochondrial fusion/division. It is expected to provide new ideas for clinical AMI-CS and identify potential complications targets.
