Effect Of QDTMT On LOX1,tPA,PAI-1,CD40mRNA Expression Of Athersclerosis Rat

Normally,the activity fibrinolysis in vivo is banlanced by tPA and PAI-1.There are two kinds of PAI-1.one is active ,the other is no activity.The frist one associsted with tPA will lose its activity.The banlance of tPA and PAI-1 decides the level of the activity of fibrinolysis. tPA can active P1g to Plm.This will lead to extracellular matrix degradation and fibrinolysis. Plm can active pro-TGF-B to active one too.The latter can inhibit the proliferation of smooth muscle cells. There is a report that expression of PAI-1 in athersclerotic vascular has a significant correlation with the degree of AS.Many experiments indicate that LDL, OX-LDL TG LPC and unsaturted fatty acids will demage endothelial cells.the increase of OX-LDL will high the receptor of LDL(LOX1) in endothelial cells.This may a main reason of endothelial cells lesion. Then the upregulation of PAI-1 will lead to thrombosis and the decrease of Plm.This will aggravate endothelial cells lesion and smoth muscle cells proliferation. So ,the decrease of fibrinolytic activity may play an important role in coronary diseases.Many evidences indicate that the interacion of many agents lead to AS. These agents include lipid metabolism, blood-cogulation factors, cellular factors, hemodynamics loading and soon.CD401igand is a important passway between immunologic cells.The interaction of CD40and CD40L regulates the imflamatory reaction from endothelial cells,smooth muscle cells and macrophage in atheromatous plaque. CD40 can make the imflamatory reacion severer, cause thrombosis and fibrosis.The combination of CD40 and CD40L in macrophage will upregulate ICAM-l,B7-l,B7-2 and MHC II .At meantime, this will accelerate the expression of CD40. Investigation of the change of CD40 make us know the lesion of AS partly. CD40 is expressed in endothelial cells,smooth muscle cells.Many cellular factors will regulate it and ICAM-1.In the first part of our experiments, 72 male SD rats were divided into six experimental groups(n=12).A:Control group; B:Model group; C:QDTMTmin group(0.36g/kg/d);D:QDTMTmid group (1.08g/kg/d);E: QDTMTmax group (3.24g/kg/d); F: Simvas-tatin group(4mg/kg/d).After 14 weeks,we assaied TC TG LDL the activity of tPA and PAI-1. we want to reveal the relationship of hyperlipemia and fibrinolysis.At meantime we estimated the influence of QDTMT on them.In the second part of our experiment , we observed the different level of the endothelial cell's lesion and the change of SOD. MDA.At the same time, the expression of tPA. PAI-1 LOX1 on aorta in every group was detected by reverse transcript polymerse chain reaction (RT-PCR). we want to reveal whether OX-LDL can cause the lesion of endothelial cells,increase LOXl and PAI-1mRNA.If QDTMT can relieve the lesion of endothelial cells, banlanc the fibribolytic system through reduction of LOX1 PAI-1mRNA.In the thrid part of our experiments, we detected the expression of CD40mRNA on aorta and monouncleus cells in every group.we want to learn the influence of QDTMTon CD40-CD40L signal system through immunoloregulation. The results were as follows:1. TC TG LDL of model group was higher than control group .TC TG LDLwere decreased when the rats were given QDTMT.The activity of PAI-1 was decreased,while tPA was increased. This tendency dependeds on dose.2. proliferation of the AS rats aorta and the lesion of endothelial cells were servere. The expression of LOX1 PAI-1 mRNA increased and the tPAmRNA have no transparent change.MDA in plasm was incresed ,while SOD was decresed. QDTMT can reduce the expression of LOX1 and PAI-1mRNA to downregulate the lesion of endothelial cells.At meantime, it can downregulate the MDA,upregulate the SOD to reduce the oxidation of LDL. This tendency dependeds on dose.3. The expression of CD40 on aorta and monouncleus cells in atherosclerosis rats was increased . QDTMT could reduce the expression of CD40. This tendency dependeds on dose.In our work,we want to...