Effects of glycine and methylprednisolone on hemorrhagic shock in rats

BACKGROUND: Methylprednisolone (MP), a synthetic glucocorticosteroid, has been broadly studied in experiments on endotoxin-induced shock and septic shock. This study was designed to ascertain whether glycine and MP can protect against organ injury and death caused by hemorrhagic shock, and to elucidate the underlying mechanisms of these protective effects in rats. METHOD: To establish a shock model, Wistar rats were bled to maintain mean arterial pressure at 30-50 mmHg for 1 hour and subsequently resuscitated with the shed blood and normal saline. Just prior to resuscitation, the rats were randomly assigned to four groups: sham group (operation performed without inducing shock), shock group, shock + glycine group (glycine injected at the beginning of resuscitation) and shock + MP group (MP injected at the beginning of resuscitation). RESULTS: (1) Seventy-two hours after resuscitation, the survival rate of rats from the shock group had decreased to 20%, while the survival rates of rats from the shock + glycine and shock + MP groups were 77.8% and 80%, respectively. The difference was significant (P <0.05). (2) Eighteen hours after resuscitation, pathological alterations in the organs of the rats were apparent. In rats from the shock group, edema, interstitial leukocyte infiltration, and cellular degeneration occurred in the liver, lungs, kidneys, and heart. Glycine and MP reduced these pathological changes significantly. (3) Eighteen hours after resuscitation, the levels of creatine phosphokinase, transaminases, and creatine were elevated significantly in rats from the shock group, indicating injury to the heart, liver, and kidneys, while these levels were elevated only slightly in the shock + glycine and shock + MP groups. The differences were significant (P <0.01). (4) There were significant increases in intracellular calcium and production of tumor necrosis factor (TNF-alpha) by isolated Kupffer cells stimulated by endotoxin after hemorrhagic shock. These changes were completely prevented by glycine and MP (P <0.01). CONCLUSION: Glycine and MP reduce organ injury and mortality caused by hemorrhagic shock by preventing increase of intracellular calcium levels in Kupffer cell, suppressing Kupffer cell activation, decreasing the production of TNF-alpha by Kupffer cells, and blocking systemic inflammatory responses.