| Objective: To study the protective effects and possible mechanisms of the hypertonic saline solution on intestine and remote organs (liver and lung ) injuries induced by intestinal ischemia reperfusion; To investigate the rule of organ protection by hypertonic saline.Methods: Rabbits were randomly assigned to control group (no treatment, no superior mesenteric artery occlusion[SMAO] , n=18), ischemia reperfusion group (no treatment,no SMA0,n=18), NS group (6mL/kg 0.9% NS, SMAO,n=18), 4%HS group (6mL/kg 4%HS, SMAO,n=18), 7.5%HS group (6mL/kg 7.5%HS, SMAO,n=18), 7.5%HS delayed group (6mL/kg 7.5%HS delayed, SMAO,n=18). The SMAO was clamped for 60 minutes and boluses given 5 minutes before clamp removal. But in 7.5%HS delayed group hypertonic saline was infused two hours after reperfusion. Serum lipopolysaccharide (LPS ) and D-lac as markers of gut barrier, serum TNF-α, MCP-I, IL-10 and ICAM-1 as markers of systemic inflammation response , serum ALT and AST as markers of liver injury were detected before ischemia and 2,4,6 hours after reperfusion .At the same time arterial blood gas analysis was performed for Na~+,CL~- and PH. After 6 hours of reperfusion, ileum ,liver and lungs of 8 rabbits each group were harvested for myeloperoxidase (MPO) as an index of neutrophil mediated injury, superoxide dismutase (SOD )and malondialdehyde (MDA) as an index of oxygen free radical mediated injury, analysis of histologic injury of gut and lung,and analysis of apoptosis of enteric epithelium. The survival time of Other 10 rabbits each group was observed.Results: (1) The markers of gut barrier: LPS, D-lac and inflammation factors:TNF-α, MCP-I, ICAM-1 significantly increased after intestinal reperfusion ,reaching peak after 2 hours of reperfusion ; markers of liver injury:ALT and AST increased significantly, and they reached peak respectively at the time 4 and 6 hours after reperfusion; intestinal pathology showed intestinal villi defect, swelling obviously,ulcer,perivascular hemorrhage, neutrophil infiltration and basal fracture; Apoptosis of intestinal epithelial cells increased ;lung pathology showed congestive, interstitial pulmonary edema, inflammatory exudate, alveolar wall destruction. (2) There are no significant difference of intestinal injury, systemic inflammatory mediators, as well as liver and lung injury between NS group (isotonic liquid treatment group) and ischemia reperfusion group. (3) In 4%HS group ,intestinal injury, systemic inflammatory mediators, as well as liver and lung injury reduced ; survival time of rabbits extended, but apoptosis of intestinal epithelial cells increased. (4) In 7.5%HS group,intestinal injury, systemic inflammatory mediators, as well as liver and lung injury improved more than 4%HS group; survival time of rabbits extended longer than 4%HS group, but apoptosis of intestinal epithelial cells increased more than 4%HS group. (5) In 7.5%HS delayed group, there are no significant difference of intestinal injury, systemic inflammatory mediators, as well as liver and lung injury as ischemia reperfusion group. But the survival time of rabbits decreased significantly.Conclusion: (1) Intestinal ischemia-reperfusion injury leaded to the injury of gut, as well as the remote organs. (2) Hypertonic saline had the protective effect on intestine and remote organs injuries induced by intestinal ischemia reperfusion. (3)Hypertonic saline could modulate systemic inflammatory response, regulate the balance between pro-inflammatory and anti-inflammatory response. (4) With the increasing concentration of hypertonic saline from 0.9% to 7.5%, the protective effects on organs function were gradually strengthened. (5) Hypertonic environment could promote apoptosis of intestinal epithelial cells by ischemic reperfusion, avoiding necrosis . (6) Hypertonic saline should be used early as tool of systemic inflammatory response limitation, otherwise could even worse systemic inflammatory response. |
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