Effects of Malate Ringer's solution on myocardial injury in sepsis and enforcement effects of TPP@PAMAM-MR

Abstract

Background Myocardial dysfunction played a vital role in organ damage after sepsis. Fluid resuscitation was the essential treatment in which Lactate Ringer's solution (LR) was commonly used. Since LR easily led to hyperlactatemia, its resuscitation effect was limited. Malate Ringer's solution (MR) was a new resuscitation crystal liquid. Whether MR had a protective effect on myocardial injury in sepsis and the relevant mechanism need to be studied. Methods The cecal ligation and puncture (CLP) inducing septic model and lipopolysaccharide (LPS) stimulating cardiomyocytes were used, and the cardiac function, the morphology and function of mitochondria were observed. The protective mechanism of MR on myocardial injury was explored by proteomics. Then the effects of TPP@PAMAM-MR, which consisted of the mitochondria- targeting polymer embodied malic acid, was further observed. Results Compared with LR, MR resuscitation significantly prolonged survival time, improved the cardiac function, alleviated the damages of liver, kidney and lung following sepsis in rats. The proteomics of myocardial tissue showed that differently expressed proteins between MR and LR infusion involved oxidative phosphorylation, apoptosis. Further study found that MR decreased ROS, improved the mitochondrial morphology and function, and ultimately enhanced mitochondrial respiration and promoted ATP production. Moreover, MR infusion decreased the expression of apoptosis-related proteins and increased the expression of anti-apoptotic proteins. TPP@PAMAM@MA was a polymer formed by wrapping l-malic acid with poly amido amine (PAMAM) modified triphenylphosphine material. TPP@PAMAM-MR (TPP-MR), which was synthesized by replacing the l-malic acid of MR with TPP@PAMAM@MA, was more efficient in targeting myocardial mitochondria and was superior to MR in protecting the sepsis-inducing myocardial injury. Conclusion MR was suitable for protecting myocardial injury after sepsis. The mechanism was related to MR improving the function and morphology of cardiomyocyte mitochondria and inhibiting cardiomyocyte apoptosis. The protective effect of TPP-MR was superior to MR.

The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis

“… 29 It’s reported that Malate Ringer’s fluid reduced myocardial injury in septic rats by improving mitochondrial function and inhibiting apoptosis, with L-malate playing a crucial role. 13 Our TPP@PAMAM encapsulating L-malate to form RPP@PAMAM@MA was confirmed in preliminary studies to target myocardial mitochondria, reducing consumption and delivering more L-malate to myocardial mitochondria, providing more raw materials for ATP synthesis.…”

“… 12 Our previous study indicated that TPP-MR significantly protected against myocardial injury in sepsis. 13 However, it remained unclear whether TPP-MR offered protection against myocardial injury in hemorrhagic shock.…”

VDAC2 malonylation participates in sepsis-induced myocardial dysfunction via mitochondrial-related ferroptosis

“…The room maintained a temperature of 23-25°C and a relative humidity of 40%-70%. The rat sepsis model was established through cecal ligation and puncture (CLP) according to a previous study 24 - 25 . After 12 hours of CLP, the rats were sacrificed, and their hearts were collected for further research.…”