Protective Effects Of Glycoprotein ⅡB/Ⅲa Receptor Inhibitors On The Sepsis-induced Lung, Liver And Kidney Injury Of Rat

ObjectiveTo investigate the role of eptifibatide, a glycoprotein Ilb/IIIa receptor inhibitor, in the protection of lung, liver and kidney in sepsis, cecal ligation and puncture (CLP) of rat is used as the model of sepsis, which provide theoretical basis for clinical treatment.MethodSixty-four adult male SD rats were randomly assigned into three groups:sham group (n=16), CLP group (n=24) and CLP+eptifibatide group (n=24). Each group after operation was averagely divided into6h,10h,14h and18h four subgroups. The rats in sham group received no administration. The rats in CLP group only faced CLP operation. The rats in CLP+eptifibatide group were given eptifibatide (7.5mg/kg) by caudal vein administration at4h、8h、12h and16h after CLP. Then all rats would face sacrifice through bloodletting. Blood sample would be routinely reserved for investigating hepatic and renal function, and the lung, liver and kidney tissues were took out for myeloperoxidase (MPO) activity, micro vascular permeability changes, endothelial cell apoptotic indexes (AI), morphological observation and histopathological score and wet/dry weight ratio (W/D) of tissue.Result1. The general situation of rats after the operation was observed:The rats in the Sham group recovery of anesthesia earlier than those in other groups and can as usual activities. No abdominal dropsy and offensive odor were found when laparotomy of rats. The rats in CLP group recovery of anesthesia later, and irritability, depressed with inaction, and tachypnea. When the abdomen was opened, turbidity bloody ascites and offensive odor was found and bowels looked edema. Cecum was blacked in CLP group. Compared with CLP group, the manifestations in the rats of eptifibatide injection group were better. 2. The change of MPO activity, micro vascular permeability changes and endothelial cell AI in tissue of every group:the lung, liver and kidney tissues of rats were observed impairment since6h after CLP operation, and MPO activity, micro vascular permeability and endothelial cell AI of all tissues gradually worsened and peaked at18h after CLP operation.3. Lung, liver and kidney morphology and hepatic and renal function on each subgroup of epidemic rat:The phenomenon of alveolar expansion and collapse was observed starting from6hours. The wide alveolar occlusion, severely exudation of red cell and micro thrombosis were showed at10hour, and gradually worsened at14h after CLP operation. Widened alveolar hemorrhage, pulmonary interstitial hyperemia edema and focal atelectasis were captured at18h after CLP operation. In the pathological lesion of liver tissue, mild swelling liver cells, loose cytoplasm, unkempt hepatic lobule was observed starting from6hours. Hepatic sinus cavity and portal area were infiltrated with inflammatory cells at10hour, and gradually worsened at14h after CLP operation. Widened hepatic sinus gap and point necrosis were captured at18h after CLP operation. In the pathological lesion of kidney tissue, significantly shrinking glomerular, degenerative renal tubular epithelial cells and blood stasis of capillary were observed in6hours subgroup and increased aggravated progressively. Serious pathological damage were observed at14h after CLP operation, containing expansive lumen of the renal tubular, tube formation, severely inflammatory infiltrative renal interstation, epithelial exfoliation. It is worth noting that histopathologic gradings gradually increased with time going and showed significant differences between any two subgroups (P<0.05). There was a significant difference on expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the level of urea of10hours subgroup and creatinine of14hours subgroup between sham group and CLP group (P<0.05).4. Lung, liver and kidney morphology on each subgroup of epidemic rat following eptifibatide treatment:Compared with the CLP group, CLP+eptifibatide rats owned weaker MPO activity (P<0.05), lower micro vascular permeability (P<0.05) and less obvious pathological damage and pathological score (P<0.05) in lung, liver and kidney tissue and lower W/D ratio in lung tissue (P<0.05) at any point in time. But beyond that, CLP+eptifibatide rats showed lower apoptosis rate of micro vascular endothelial cell in lung, liver and kidney tissue at any point in time (P<0.05). In addition, compared with the CLP group,10h subgroup performed lower level of ALT and AST (P<0.05) and BUN (P<0.05), and14h subgroup exhibited lower level of Cr (P<0.05). Conclusion1. Sepsis can lead to lung, liver and kidney tissue damage characterized by various contents, including MPO activity, micro vascular permeability, pathological damage and apoptosis rate of micro vascular endothelial cells. As time goes on, septic rats show greater MPO activity, micro vascular permeability and W/D ratio, more obvious pathological damage and pathological score and more sever hepatic and renal function.2. As a glycoprotein Ⅱb/Ⅲa receptor inhibitor, eptifibatide can protect lung, liver and kidney tissue for rats that have underwent CLP treatment through different ways, including reduced apoptosis rate of micro vascular endothelial cells, and improved pulmonary micro vascular permeability and hepatic and renal function.