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Objective To determine the effects of intraperitoneal resuscitation (PR) with different concentrations of sodium pyruvate (PY) on intestinal ischemia reperfusion injury in rats hemorrhagic shock (HS). Methods Sixty rats were randomly assigned to six groups. These included: group SHAM, intravenous resuscitation only (VR) group, and four PR groups based on resuscitation fluid: glucose-lactate-based peritoneal dialysis solution (LA), and PY-1.1%, PY-1.6%, and PY-2.2% (concentrations in grams/dL). Mean arterial pressure (MAP) was monitored continuously. Blood pH, base excess (BE), lactate, intestinal myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), activated caspase-3, and zonula occludens-1 (ZO-1) were measured; intestinal mucosal damage index (IMDI) and subcellular changes were observed; apoptotic index (AI) was calculated. Results Three hours after resuscitation, in PY groups, MPO, MDA, IMDI, AI, TNF-alpha, and IL-6 were significantly lower than VR and LA groups, while pH and BE were higher. PY groups showed less expression of activated caspase-3 but elevated ZO-1. Among PY groups, group PY-1.1% had the lowest MPO, MDA and TNF-alpha, and had less pathological damage and subcellular changes than other experimental groups. Conclusions PR using PY solution combined with VR provided protection against intestinal ischemia-reperfusion injury following HS and resuscitation. Under the same hypertonic condition, 1.1% PY solution showed significant advantages compared with 2.2% and 1.6% solutions. The underlying mechanisms may include the maintenance of hemodynamic stability, regulation of homeostasis, inhibition of oxidative stress and inflammation, and protection of intestinal epithelial tight junction barrier function.

The bacterial infection following thermal injury is a very important factor of excessive inflammatory response and multiple organ damage. Muramyl dipeptide (MDP) is the key structure of gram-positive bacteria and gram-negative bacteria triggering the innate immune system. The aim of the present study was to determine the effect of MDP on thermal injury-induced inflammatory responses, organ function injury, and mortality in rats. Fifty male Sprague-Dawlay rats were randomly divided into three groups: normal control group, scald group, and MDP group. Scald group only suffered 20% total body surface area third-degree thermal injury. Muramyl dipeptide 5 mg·kg was administered through the femoral vein at 24 h after thermal injury in the MDP group. Plasma inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. An additional 90 male Sprague-Dawley rats were randomly divided into three groups to observe the survival rate in 72 h. Plasma levels of interleukin-6, interleukin-10, interferon-γ, and high-mobility group box 1; the white blood cell counts; the serum concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatine kinase isoenzyme-MB, blood urea nitrogen, and creatinine; and the activity of lung tissue myeloperoxidase significantly increased after thermal injury alone. Compared with the scald group, MDP led to more serious inflammatory responses and organ function damage and higher mortality (P < 0.05, respectively). These data indicate that MDP exacerbates thermal injury-induced inflammatory cytokine production, accompanied by multiple organ dysfunction syndrome and high mortality in rats.

Acute lung injury (ALI) leading to respiratory distress is a common sequela of shock or trauma. The toll-like receptors (TLRs) stand at the interface of innate immune activation in the settings of both infection and sterile injury by responding to a variety of microbial and endogenous ligands alike. This work explored the effects of TLR-4 on hemorrhage-induced ALI and characterizes the signaling pathways and the mechanisms involved in noninfectious ALI. Mice underwent hemorrhagic shock and resuscitation (HSR). Arterial blood gases; expressions of TLR-4, heme oxygenase 1 (HO-1), and p38 mitogen-activated protein kinase (p38MAPK); myeloperoxidase activity; lung wet/dry ratios; and IL-10 levels in lung tissues were obtained at 6, 24, and 48 h after HSR. Hemorrhagic shock and resuscitation induced significant expressions of TLR-4, HO-1, and p38MAPK in C3H/HeN mice. IL-10 and myeloperoxidase were markedly increased at 24 h after HSR, and C3H/HeN mice had ALI with PaO2/fraction of inspired oxygen less than 300 mmHg. The induced amount of each cytokine level and the expressions of TLR-4, HO-1, and p38MAPK of C3H/HeN mice were significantly higher compared with C3H/HeJ mice. This study demonstrated that lung p38MAPK is activated after HSR, and p38MAPK inhibitor FR167653 suppresses HO-1 induction after ALI. We concluded that TLR-4 might induce HO-1 messenger RNA expression, which is probably involved in p38MAPK activation in the development of the lung dysfunction after HSR.

Anticholinergics can have protective effects against septic shock. Penehyclidine hydrochloride (PHC) is a novel anticholinergic agent exhibiting few cardiovascular side effects. This work explored the protective effects of PHC on septic mice and its mechanism. Mice were randomly divided into four groups: sham control, cecal ligation and puncture (CLP), CLP/0.3 mg/kg PHC, and CLP/0.45 mg/kg PHC, with 10 mice in each. One hour before surgery, PHC-treated mice received an intraperitoneal injection of PHC and an equal volume of saline in the other two groups. Blood plasma and tissue samples were collected at 12 h after surgery. Serum TNF-alpha, histopathology, superoxide dismutase (SOD), malondialdehyde (MDA), and expression of iNOS in lung and hepatic tissues were examined. Another 40 mice were randomly assigned to four equal groups to observe survival status during 96 h after operation. Treatment of 0.45 mg/kg PHC markedly decreased TNF-alpha, MDA content, and iNOS mRNA expression, and enhanced SOD activity (P < 0.05 and P < 0.01). Treatment of 0.45 mg/kg PHC might have a protective effect against sepsis. Its action mechanisms are probably involved in the inhibition of inflammatory factor production and suppression of iNOS mRNA expression and lipidperoxidation.