Sodium valproate inhibited apoptosis in lethally scalded rat cardiomyocytes by regulating hypoxia-inducible factor-1α expression.

This study assessed the inhibitory effect of sodium valproate (VPA) on apoptosis of cardiomyocytes in lethally scalded rats. The model of a 50% total body surface area (TBSA) third-degree full-thickness scald was produced, 48 male SD rats were randomly divided into three groups (n = 16), the sham group and the scald group were given an intraperitoneal injection of 0.25ml of saline, the scald +VPA group was given an intraperitoneal injection of VPA (300 mg/kg) after scalded, Each group was subdivided into two subgroups (n=8) according to the two observation time points of 3h and 6h after scald. Apoptotic cardiomyocytes were observed, and myocardial tissue levels of nitric oxide (NO), cysteine protease-3 (caspase-3) activity, hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), BCL2/adenovirus E1B interacting protein 3 (BNIP3) and caspase-3 protein were measured. Compared with sham scald group, severe scald elevated CK-MB, cardiomyocyte apoptosis rate, caspase-3 activity and protein levels, NO content, and HIF-1α signalling pathway proteins; whereas VPA decreased CK-MB, cardiomyocyte apoptosis rate and inhibited HIF-1α signalling pathway protein expression. In conclusion, these results suggested that VPA inhibited early cardiomyocyte apoptosis and attenuated myocardial injury in lethally scalded rats, which may be related to the regulation of the HIF-1α signalling pathway.

Establishment of a Bama miniature pig burn model with different burn depths.

Background: The skin morphological characteristics of the Bama miniature pig are very similar to those of humans; thus, the Bama miniature pig is an ideal choice for establishing a skin burn model. Methods: In this study, 6 ordinary, male, Bama miniature pigs (weight: 23-28 kg and length: 71-75 cm) were used to establish burn models. A mixture of 1 mg of Ketamine and Sumianxin II was used for Bama miniature pigs anesthetizing, and 1 mg of Pentobarbital sodium was added as necessary. The different burn depths were made using a continuous pressure of 1 kg and contact times of 0 s, 10 s, 15 s, 20 s, 25 s, 30 s, 35 s, 40 s, and 45 s by the newly invented electronic burn instrument. The burned tissues were collected and examined with hematoxylin and eosin (H&E) and Masson staining. Results: Burning for 10-15 s caused a first-degree burn; the blood vessels in the superficial dermis were dilated and congested, and necrosis occurred above the basal layer of the epidermis. Burning for 20-25 s caused a superficial partial-thickness burn; the whole epidermal layer was necrotic, and the collagen fibers were slightly deformed. Burning for 30-35 s caused a deep partial-thickness burn; the whole epidermal layer and dermal layers were necrotic with leukocyte infiltration zones, and the collagen fibers were disordered, degenerated, and necrotized. Burning for 40-45 s caused a third-degree burn; the skin layers and adipose tissues were necrotic, and the thick blood vessels in the skin adipose tissues were full of disintegrated and agglutinated red blood cells. Conclusions: Stable burn depth models of Bama miniature pigs were constructed using a new and innovative electronic burn instrument. Our findings provide a basis for further research on the burn mechanism and evaluations of therapeutic drugs.

Protective effect of restrictive resuscitation on vascular endothelial glycocalyx in pigs with traumatic hemorrhagic shock.

Background: Hemorrhagic shock is the leading cause of early traumatic death. Research and discussion on restrictive fluid resuscitation have been ongoing for many years. The purpose of this study was to explore whether restrictive resuscitation can inhibit the shedding of vascular endothelial glycocalyx in the prehospital treatment of traumatic hemorrhagic shock pigs. Methods: Landrace pigs were randomly divided into a restrictive resuscitation group (restrictive group) and a conventional resuscitation group (conventional group), with 6 pigs in each group. The gunshot caused a rupture of the pig's receding right femoral artery, and the average arterial pressure was 40-45 mmHg stable for 30 minutes, which was defined as a successful shock model. The end point of resuscitation in the restrictive group was a mean arterial pressure (MAP) of 55-60 mmHg for 30 minutes, and the end point of resuscitation in the conventional group was a MAP of 70-75 mmHg for 30 minutes. The results of arterial blood gas analysis, hemodynamic indicators, endothelial glycocalyx damage and shedding marker Syndecan1 and soluble thrombomodulin (sTM) expression levels were compared between the two groups of experimental pigs after resuscitation. Results: The two groups of experimental pigs had the same baseline levels before injury in age, body weight, blood loss, cardiac output index, cardiac function index (CFI), extravascular lung water index (ELWI), and pulmonary vascular permeability index (PVPI). The arterial blood gas analysis of the two experimental pigs showed no significant difference in carbon dioxide partial pressure, oxygen partial pressure, blood oxygen saturation, or blood lactic acid after resuscitation. The difference in cardiac output index and CFI at the end of resuscitation between the two groups was not statistically significant; the absolute value and percentage of Syndecan1 level increase in the restrictive resuscitation group were lower than those in the conventional resuscitation group, and the difference was statistically significant. Conclusions: Compared with full resuscitation in a short period of prehospital treatment, restrictive resuscitation can achieve a similar effect in maintaining tissue oxygen supply and can reduce the loss of vascular endothelial glycocalyx to a certain extent.

Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction.

AIM: To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L, P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group (P < 0.05). CONCLUSION: DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.