ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of combination of glycine and methylprednisolone (MP) on Kupffer cells in liver of rats suffered from hemorrhagic shock.</p><p><b>METHODS</b>Fifty Wistar rats were bled to establish the shock model and subsequently resuscitated with shed blood and normal saline. Just prior to resuscitation, the rats were randomly assigned to 5 groups: sham group, shock group, shock + glycine group, shock + MP group and shock + glycine + MP group. The intracellular calcium concentration and the level of tumor necrosis factor alpha (TNF alpha) in the culture medium of Kupffer cells were determined after stimulation with different concentrations (1, 10, 100 and 1000 ng/ml) of lipopolysaccharide (LPS).</p><p><b>RESULTS</b>Concentration of intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by LPS were elevated significantly in the rats with hemorrhagic shock, which were totally prevented by glycine + MP compared with other groups (P < 0.005).</p><p><b>CONCLUSIONS</b>The combination of glycine and MP prevents the increase of intracellular calcium of Kupffer cell, suppress Kupffer cell activation, decrease the production of TNF-alpha of Kupffer cell and block systemic inflammatory responses more effectively than single administer of glycine or MP.</p>
Subject(s)
Animals , Female , Male , Rats , Calcium , Metabolism , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Drug , Glycine , Pharmacology , Therapeutic Uses , Kupffer Cells , Pathology , Physiology , Liver , Metabolism , Pathology , Methylprednisolone , Pharmacology , Therapeutic Uses , Random Allocation , Rats, Wistar , Shock, Hemorrhagic , Drug Therapy , Pathology , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
<p><b>AIM</b>To observe the effects of hypercapnia on nuclear factor-kappaB and TNF-alpha in acute lung injury models.</p><p><b>METHODS</b>Six of the twenty-two healthy New Zealand white rabbits were randomly allocated to control group (Group C), the other sixteen rabbits were injected with oleic acid (0.1 ml/kg) intravenously, then were randomized to normocapnic group (Group N, n = 8) versus hypercapnic group (Group H, n = 8). TNF-alpha of serum and bronchoalveolar lavage fluid (BALF) and the expression of nuclear factor-kappaB in the lung were analyzed after three hours' mechanical ventilation.</p><p><b>RESULTS</b>TNF-alpha of serum and bronchoalveolar lavage fluid in Group N and H was significantly higher than that in Group C (P < 0.01), and that of Group N was higher than that of Group H (P < 0.05). The expression of nuclear factor-kappaB in Group H was less than that in Group N by both immunohistochemistry and Western-blot analysis. Peak airway pressure in Group H was significantly lower than that in Group N and the dynamic lung compliance was significantly higher than that in Group N (P < 0.05). PaO2 in Group H was significantly higher than that in Group N (P < 0.05). Histologic damage in Group N was significantly severer than that in Group H.</p><p><b>CONCLUSION</b>Hypercapnia is protective in this in vivo model of ALl. The mechanisms might be associated with the prohibition of nuclear factor-kappaB and then the decreased expression of TNF-alpha by hypercapnia.</p>