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

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.

Lycium barbarum polysaccharide improves traumatic cognition via reversing imbalance of apoptosis/regeneration in hippocampal neurons after stress.

AIMS: Previous studies in our laboratory have demonstrated the increased neuronal apoptosis in the hippocampus and abnormal hippocampal morphology after severe stress, which directly correlates to the pathogenesis of post-traumatic stress disorder (PTSD). This study aims to investigate the effects of Lycium barbarum polysaccharide (LBP) on intrusive memory of posttraumatic stress in rats, and to analyze the mechanism of regeneration/apoptosis balance in the hippocampal neurons. MAIN METHODS: The experimental rats received 20 inescapable electric foot shocks in an enclosed box for six times in three days. The rats were treated by intragastric administration of LBP (20mg/kg/day) for 3 days before stress in the stress plus prophylactic group, and for 28 days after stress in the stress plus therapeutic group. The emotion, intrusive memory-related behavior (freezing, open field, pain latency, spatial cognition), hippocampus cell morphology, and relation of neurogenesis and apoptosis in dental gyrus of the hippocampus were observed. The hippocampus volume was evaluated by stereology. Meanwhile, the neurogenesis and apoptosis were analyzed with 5-bromo-2'-deoxyuridine and terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) method. KEY FINDINGS: The treatment of LBP in pre-stress and post-stress had obvious beneficial effect on the behaviors and neurogenesis. The stressed rats showed improvement of intrusive memory related cognition defect, alleviation of the apoptosis in the hippocampus and recovery for the neurogenesis, which was related to the hippocampus volume after LBP treatment. SIGNIFICANCE: LBP treatment might effectively improve the traumatic cognition defect induced by severe stress and be useful for the intrusive memory-related cognition recovery.