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Therapeutic Effect of Pulmonary Hemocoagulas Delivery on Neonatal Rats with Acute Lung Hemorrhage Induced by Lipopolysaccharide

Author: ZhangZhiHong
Tutor: WangDianHua；ZhangXuan
School: Kunming Medical College
Course: Pharmacology
Keywords: Acute lung hemorrhage hemocoagulase pulmonary delivery Lipopolysaccharide
CLC: R96
Type: Master's thesis
Year: 2009
Downloads: 36
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Abstract

Objective Acute lung hemorrhage is a common critical clinical disease with high mortality and morbidity.Pathogenesis of acute lung hemorrhage is complicated and unclear,therefore investigating effective therapeutic method of acute lung hemorrhage is important.The purpose of this study was to explore therapeutic effect of pulmonary hemocoagulase delivery on neonatal rats with acute lung hemorrhage induced by lipopolysaccharide.Methods Healthy neonatal Sprague-Dawley rats were ramdomly divided into 5 groups:①Control group,animals were free of any treatment;②Hemocoagulas group,animals.were given hemocoagulas(2.5 Ku/kg) intratrache -ally;③Acute lung hemorrhage group,animals were given Lipopolysaccharide(5 mg/kg) intraperitoneally;④Pulmonary Hemocoagulas delivery group,animals received hemocoagulas(2.5 Ku/kg) intratracheally after intraperitoneal injection of Lipopolysacchadde(5 mg/kg).⑤Intravenous injection of Hemocoagulas group: animals received hemocoagulas(2.5 Ku/kg) intravenously alter intraperitoneal injection of Lipopolysaccharide(5 mg/kg).The changes of bleeding time(BT), Coagulation time(CT),Prothrombin Time(PT)and the contents of Fibriviogen,Lung Myeloperoxidase(MPO) acticity,and Lung wet/dry weight ratio were measured at 1 h, 2 h and 4 h.after delivery of Hemocoagulase,Lung Myeloperoxidase acticity was measured by MPO assay kit.The statistical analysis was carried out by SPSS 11.5 for Windows.Data were statistically analyzed using a one-way analysis of variance followed by the Dunnett,s multiple comparison test.P<0.05 was considered statistically significant.Results①The changes of BT,CT,PT and Fibriviogen: Compared with control group and hemocoagulas group,BT and CT of rats in acute lung hemorrhage group were obviously longer;compared with acute lung hemorrhage group,BT and CT of rats in pulmonary hemocoagulas delivery group and intravenous injection of hemocoagulas group were shorter but still longer than control group and hemocoagulas group,and the lung hemorrahage was evidently meliorated;BT and CT of rats in pulmonary hemocoagulas delivery group were shorter than intravenous injection of hemocoagulas group(P<0.05),In acute lung hemorrhage group,PT of rats were prolonged and the contents of Fibriviogen decreased obviously;These changes were meliorated in pulmonary hemocoagulas delivery group and intravenous injection of hemocoagulas group.②Histopathological evaluation:Typical acute hemorrhage in the lung were observed in acute lung hemorrhage group,including alveolar congestion,hemorrhage,edema,infiltration of neutrophils in the airspace or vessel wall,thickness of the alveolar wall,swelling of mitocondria in endothelial cells, injury of basement membrane,blood cells in airspace and interstitial tissue; Pathological changes were relieved obviously in pulmonary hemocoagulas delivery group and intravenous injection of hemocoagulas group and the pulmonary hemocoagulas delivery was superior to intravenous injection of hemocoagulas; Obvious pathological changes obvious were not found in control group and hemocoagulas group.③Lung W/D ratios:The lung W/D ratios of rats in acute lung hemorrhage groups were significantly higher than those in control group and hemorrhage group((P<0.05);The lung W/D ratios of rats were significantly lower in pulmonary hemocoagulas delivery group and intravenous injection of hemocoagulas group than in acute lung hemorrhage group,but still higher than in control group and hemocoagulas group.④Lung MPO activity:The lung MPO activity in acute lung hemorrhage group was significantly higher than that in control group and hemorrhage group(P<0.05);The lung MPO activity was significantly lower in pulmonary hemocoagulas delivery group and intravenous injection of hemocoagulas group,but still higher than in control group and hemocoagulas group.Conclusions①Intraperitoneal injection of Lipopolysaccharide can induce acute lung hemorrhage in neonatal rats,and hemorrhage is mainly in airspace and interstitial tissue.②Pulmonary hemocoagulas delivery and intravenous injection of hemocoagulas can alleviate the injury of vascular walls and inflammation of lung tissues,shorten bleeding time,coagulation time,prothrombin time,lessen the decrease of fibriviogen, alleviate lung hemorrhage and edema,and reduce infiltration of inflammatory cells in neonatal rats with acute lung hemorrhage.③Pulmonary hemocoagulas delivery is more effective than intravenous injection of hemocoagulas in shortening BT and CT of neonatal rats,and alleviating the injury of lung vascular walls and tissues. Therefore pulmonary hemocoagulase delivery is superior to intravenous injection of hemocoagulas in neonatal rats with acute lung hemorrhage.④Pulmonary hemocoagulase delivery has no effects on the lung tissues of normal rats in short time.

Therapeutic Effect of Pulmonary Hemocoagulas Delivery on Neonatal Rats with Acute Lung Hemorrhage Induced by Lipopolysaccharide

Abstract

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