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The Change Of Adhesion Molecule In Acute Pulmonary Thromboemlism And Effect Of Safflor Injection

Posted on:2006-02-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:J C ZhangFull Text:PDF
GTID:1104360212490200Subject:Internal Medicine : Respiratory System Disease
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Objective To discuss the expression of intercellular adhesion-1 (ICAM-1), P-selectin(Ps) in the vascular endothelial cell in acute pulmonary thromboembolism and effect of urokinase(UK).Methods Rats were randomly divided into control group, model group, urokinase-treated group. Pulmonary thromboembolism(PTE) model was established by intravenous injection of auto-blood clots. All rats were sacrificed on 1 hour, 3 hour, 24hour, 72hour, 120hour after treatment respectively. 1ml vascular blood was withdrawn from each animal to measure blood gas analysis. The expression of ICAM-1, P-selectin in the vascular endothelial cell were evaluated by immunohistochemical method and ICAM-1 mRNA, P-selectin mRNA was detected by in situ hybridization.Results The notable embolism in pulmonary arteries, inflammatory cell infiltration around alveoli could be found by microscopy. The expression of ICAM-1 was elevated quickly at 3 hour after embolization (P<0.01).The expression of P-selectin was higher at 1 hour after embolization than that before embolization(P<0.01). whereras UK treated rat showed embolism, hemorrhages relative lighten but inflammatory reaction aggravation; the expression of ICAM-1, P-selectin in the vascular endothelial cell raised again.Conclusion In the PTE, cell adhesion molecule play an important role to acute lung injuries. Thromblytic therapy can improve blood gas, but inflammatory reaction is still obvious and could relate to injury of ischemia reperfusion. Thus, thromblytic and anti-inflammatory therapy are same important in acute PTE. Objective To observe the change of nitric oxide(NO) in acute pulmonary thromboembolism and evaluate the effect of safflor infection or urokinase(UK).Methods Rats were randomly divided into control group(C-group), model group(M-group), UK therapy group, SA therapy group and UK+SA therapy group.Rat PTE model was established by intravenous injection autologous blood clots. All rats were sacrificed on 1 hour, 3 hour, 24hour, 72hour, 120hour after treatment respectively. 1ml vascular blood was withdrawn from each animal to measure blood gas analysis. The pathological changes of lung were examined with light microscope. The expression of ICAM-1, P-selectin in the vascular endothelial cell were evaluated by immunohistochemical method and ICAM-1 mRNA, P-selectin mRNA was detected by in situ hybridization.The plasma of NO were measured by biochemisty. By using RT-PCR method, expression of PKC in lung were examined.Results1. Histopathologic analysis: PTE, UK and SA group lung histopathologic injury showed evidently; whereas, UK+SA group lung pathological change were declined markedly; UK and UK+SA group the blood gas analysis were ameliorated markedly.2. Immunohistochemistry and situ hybridization show: In SA and UK+SA group, the expression of P-selectin in lung vascular endothelium , compared with M and UK group, were decreased significantly(P<0.01). Expect 1 hour after treatment, the expression of ICAM-1 in lung vascular endothelium in SA and UK+SA group, compared with M and UK group, were decreased significantly(P<0.05).3. The level of NO in blood: The level of NO begun to elevated at 1 hour after embolization, and reach a climax at 120 hour. In UK, SA, UK+SA group, the level of NO in blood was all increased. The group which was the most increament was the UK+SA group. compared with M, UK group, were decreased significantly(P<0.05).4. The expression of PKC mRNA in lung: the expression of PKC mRNA in lung begun to increased at 1 hour after embolization and thromblytic, and reach a climax at 120 hour(P<0.01). In SA and UK+SA group, the expression of PKC mRNA in lung was all decreased. Compared with M , UK and SA group, the expression of PKC mRNA was the most increament in UK+SA group(P<0.05).Conclusion After the PTE, thromblytic and safflor infection can alleviate acute lung injury , increase the level of NO and down-regulate the expression of P-selectin and ICAM-1 in pulmonary vascular endothelium by depressing activation the PKC. Objective To observe the effect of serum containing safflor injection on P-selectin and ICAM- 1 in pulmonary vascular endothelium during hypoxia and reoxygenation and discuss the regulation of NF- κB pathway on P-selectin and ICAM-1. To analysis the mechanism of pulmonary ischemic/reperfusion injury after thromblytic in pulmonary thrombembolism.Methods Take rat umbilical pulmonary artery endothelial cell as study object, observe the expression of P-selectin and ICAM-1 mRNA by cell culture, RT-PCR, Western blot, Chinese herb serum experiment and cell chemistry staining method in immunofluorescence during normoxia, hypoxia and reoxygenation respectively and the effect of serum safflor injection on the expression of P-selectin and ICAM-1 mRNA after reoxygenation.Result The expressions of P-selectin and ICAM-1 mRNA in culure cell in normoxia group were not obviously difference (P<0.05) at each time point. In hypoxia group, they are increased, but compared with the normoxia group, were not obviously difference. The expression of mRNA and protein of P-selectin and ICAM-1 were all increased significantly in 1 , 6, 12 hour after reoxygenation, and the expression of NF-κ B protein was increased significantly too. Adding the saffflor injection after reoxygenation, the expression of P-selectin , ICAM-1 mRNA and NF- κ B protein were all decreased significantly at each time point , compared with normoxia and reoxygenation group, were obviously different(P 均≤0.01).Conclusion The expression of P-selectin and ICAM-1 in rat pulmonary artery endothelium during hypoxia was not changed obviously. The overexpressions of P-selectin and ICAM-1 during reoxygenation may participate the pathogenesis of ischemic/reperfusion injury after thromblytic in pulmonary thrombembolism. Salffor injection may protect the ischemic/reperfusion injury by suppressing NF- κ B.
Keywords/Search Tags:Pulmonary thromboembolism, urokinase, Adhension molecule, thromblytic-therapy, Nitric oxide, Safflor infection Protein kinase C, P-selectin, intercellular adhesion-1, pulmonary artery endothelium
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