| Objective: To evaluate effects of different vasoactive agents on the intestinal mucosal permeability in a rabbit model of septic shock and to explore the probable mechanism.Methods: A cecal ligation and puncture procedure combined with intravenous injection of Lipopolysaccharides was used to make septic shock model, sixty-three rabbits were randomly divided into 5 groups:sham operation group(group A,n=7), septic shock group (group B,n=14),dopamine group (group C,n=14) , norepinephrine combined with dobutamine group (group D,n=14)and norepinephrine combined with arginine vasopressin group(group E,n=14).7 rabbits from each group were sacrificed3 and 6 hours after septic shock, a lactulose/mannitol (L/M) ratio test and the morphological changes were performed at 3 and 6 h. The apoptosis of intestinal epithelial cells and Caspase -3 mRNA were performed respectively by Tunel and Real-time PCR. Mean arterial pressure and heart rate were continuously recorded. Results:1.The blood pressure of all the treated rabbits falls shortly after the LPS injection and falls again after a short time going up.MAP goes down to 60% of the basic MAP or below in 2 hours ,the models of septic shock in rabbits was established.2. Urine L/M ratio in septic shock groups were increased , group B at 3 and 6 h and group D at 3h was significantly higher than that in group A(P<0.01); No significant differences in the L/M ratio were found between group C and B at 3 and 6 h (P>0.05); group D, E at 3, 6 h was lower than that in group B(P<0.05); group E at 6 h was lower than that in group D(P<0.05).3. Atrophy, epithelial cells degeneration and even necrosis, extensive interstitial edema, telangiectasia in intestinal mucosa was observed in group B and C; there are a clear structure and rules of villus arrangement, the integrity of the epithelium in group D, E than those in group B .4. The irregularity and sparse of microvilli arrangement, widened of tight junctions between epithelial cells, vacuolar degeneration of the endoplasmic reticulum and mitochondria, the disappearance of mitochondrial cristae was observed in group B and C. The changes of the intestinal epithelial cells were lessened in group D and E than those in group B.5. 1) There was only few Tunel-positive cells of intestinal macosa in group A; 2) Compared with group A, the numble of apoptosis cells increased notably in group B and C at 3,6 h and in group D, E at 6h (P<0.01) . 3) Compared with group B, the numble of apoptosis cells decreased in group D and E at 3, 6h (P<0.01).6. 1) Compared with group A, The expression of Caspase-3 mRNA increased singificantly in group B, C at 3,6 h and group D at 6h (P<0.05). 2) Compared with group B, the expression of Caspase-3 mRNA decreased in group C at 6h and group D,E at 3, 6h (P<0.01).Conclusion: Intestinal mucosal were injuried severely in septic shock model. Norepinephrine combined with dobutamine or AVP relieved lesion of intestinal morphology and permeability induced by septic shock. Norepinephrine combined with dobutamine or AVP reduce the apoptosis of intestinal epithelial cells by decreasing the expression of Caspase-3 mRNA, which has a protecttive effect to the intestinal epithelium. |
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