Protective Effect of Shen‐Fu Injection on Neuronal Mitochondrial Function in a Porcine Model of Prolonged Cardiac Arrest

Abstract

Background. Shen-Fu injection (SFI) following cardiac arrest exhibits neurological effects, but its effect on neurological dysfunction is unclear. This study sought to investigate the protective effect of SFI on nerve cells in a porcine model of cardiac arrest. Methods. After eight minutes of untreated ventricular fibrillation (VF) and 2 minutes of basic life support, 24 pigs were randomized and divided into three cardiopulmonary resuscitation groups, which received central venous injection of either Shen-Fu (SFI group; 1.0 ml/kg), epinephrine (EP group; 0.02 mg/kg), or saline (SA group). Surviving pigs were sacrificed at 24 h after ROSC and brains were removed for analysis for morphologic changes of mitochondria by electron microscopy, for mitochondrial transmembrane potential (MTP) by flow cytometry, and for opening of the mitochondrial permeability transition pore (MPTP) by mitochondrial light scattering. Results. Compared with the EP and SA groups, SFI treatment reduced opening of MPTP, showing higher MMP. In addition, animals treated with SFI showed slight cerebral ultrastructure damage under the electron microscopy. Conclusion. Shen-Fu injection alleviated brain injury, improved neurological ultrastructure, stabilized membrane potential, and inhibited opening of MPTP. Therefore, SFI could significantly attenuate postresuscitation cerebral ischemia and reperfusion injury by modulating mitochondrial dysfunction of nerve cells.

DSePA Antagonizes High Glucose-Induced Neurotoxicity: Evidences for DNA Damage-Mediated p53 Phosphorylation and MAPKs and AKT Pathways

“…Depletion of Δψm will lead to the opening of the MPTP, followed by the release of cytochrome C, apoptosis-inducing factors (AIFs), SMAC/Diablo, and endonuclease G [41,42], which all contribute to mitochondria-mediated apoptosis. Much Suppressive effects of p53 SiRNA on high glucose-induced p53 phosphorylation and caspase-3 activation in PC12 cells.…”

Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open‐Label Trial

“…Shenfu has been shown in rats to decrease injury to the central nervous system after cerebral ischemia by decreasing calcium overload, suppressing inflammation, and decreasing apoptosis [ 34 ]. In addition, Shenfu can protect the brain after resuscitation by stabilizing the cellular membrane, suppressing the opening of the mitochondrial permeability transition pore, and alleviating the dysfunction of cerebral mitochondria [ 35 ]. Nevertheless, these mechanistic data are exploratory at best and additional studies are necessary to address this issue.…”

Shenfu injection provides protection for perinatal asphyxia in neonates

“…Hypoxia leads to coupling disturbances between brain function and blood flow, glutamate-propagated functional disturbances, free radical mediated changes, disturbances of signaling pathways and gene expression patterns and programmed cell death (Hossmann, 1999). Shenfu injection has been shown to attenuate post-resuscitation cerebral ischemia and reperfusion injury by modulating mitochondrial dysfunction of nerve cells (Gu et al, 2014). Our previous study also showed that shenfu injection protected neonatal hypoxic-ischemic brain injury by preventing neuron apoptosis .…”