Effect of mitochondrial transplantation on cardiopulmonary dysfunction indicators in rats with sepsis

Abstract

Sepsis is known as the leading cause of death in critically ill patients and yet no effective treatment has been identified to treat it. Cardiopulmonary disorders are one of the leading causes of death in critically ill patients with sepsis. It has recently been shown that mitochondrial transplantation can be used as a treatment in patients with myocardial ischemia and reperfusion injury, but so far no study has examined its effect on the consequences of sepsis. Therefore, we decided to study the role of mitochondrial transplantation in reducing dysfunction caused by sepsis. Methods and Materials: 60 rats were included in the study and randomly divided into 6 groups: control, sham, cecal ligation and puncture (CLP), CLP+ mitochondrial isolation buffer, intervention with one mitochondrial injection to the CLP group and intervention with two mitochondrial injections to the CLP group. Structural changes in heart tissue was graded based on cell infiltration, sarcoplasm vacuole, tissue degeneration, lateral nucleus, and fibrosis and compared between groups. Also factors related to cardiac mitochondrial function (ATP, mtROS and mitochondrial membrane potential), inflammatory cytokines (IL-6, IL-1β, TNF-α, cTnI) and genes involved in mitochondrial biogenesis in the heart (PGC-1, Sirt-1, DRP-1, Mfn-1, Mfn-2) were measured and analyzed among different groups. Results: Mitochondrial transplantation (even for one time) was able to significantly eliminate these changes or reduce them to mild changes. The increase in sepsis-induced mitochondrial ROS, following short-term and long-term mitochondrial transplantation, was significantly compensated and decreased (p <0.05 and p <0.01). However, the decrease in ATP induced by sepsis was significantly increased only after two injections of mitochondria (p <0.05). Also, a significant reduction in mitochondrial membrane potential due to sepsis gave a weak response to mitochondrial transplantation and no significant increase. Changes in the expression of mitochondrial genes due to sepsis were significant after receiving two mitochondrial transplants but were not significant at one time. Increased production of inflammatory cytokines in response to sepsis, following short-term and long-term mitochondrial transplantation, was significantly reduced in both cases.