The Effect Of Different Injury Factor On Vascular Endothelial Cell Releasing VWF, PAI-1 And T-PA

PartⅠEffect of hyperlipedemis on vWF,PAI-1 and t-PA in ratsObjective:to observe the time course effect of the hyperlipedemis on the expression levels of blood plasma early metaphase markers such as vWF,PAl-1 and t-PA in rats,and compare the difference to identifying one or several highly sensitive and specific marker(s)for vascular endothelium injury.This will guide the clinical diagnosis and therapeutics of thrombus disease.Methods:60 male Sprague-dawley rats weighting about(200±20) g were randomly divided into 6 groups.30 were intragastric administrated with high fat composition for 7 weeks(group A7,n=10), 8weeks(group A8,n=10)and 9weeks(group A9,n=10)respectively.In the meantime,30 were randomly taken as control groups:common bait vessel feeding for the same time(group C7,group C8 and group C9, n=10).All the rats in group A were intragastric administrated with certain dose of high fat composition according to their own weight everyday as well as common bait vessel feeding for 7,8 or 9 weeks.All the rats in group A were weighted every week to adjust their intragastric administration doses.When reach the setting time,the rats were sacrificed and serum were separated to detect the blood-fat immediately. Meanwhile,the pathological sections of the rats aorta artery were prepared evaluate the endothelial injury degree.The blood plasma were separated and the levels of the blood plasma TM,PAl-1,t-PA and vWF were detected by ELISA assay and statistics analysis were performed to exam the significance.Results:①the levels of TG,TC and LDL of were all elevated in the rats administrated intragastricly with high fat composition than the corresponding control groups,and the increasing level of HDL were correlated with the duration of the treatment effect at the beginning.The HDL level decresed after 9 weeks treatment.②No lesions in aortic endothelium were observed in rats from all group C using optical microscope,while pathologic lesions in aortic endothelium in rats of all group A were observed.③The amount of vWF and PAI-1 were higher in Group A compared with the control groups,while the amount of t-PA were significantly lower than those of the control groups.④Significant correlation between the periods of time of administrating high fat composition and vWF,PAl-1,t-PA were observed(r=0.852, 0.953 and -0.948,p＜0.01)Conclusion:①with the increasing duration of intragastric administration,endodermis injuries were aggravated with increasing levels of blood fat in rats.②The amount of vWF and PAI-1 in rats plasma was were gradually increased,while the level of t-PA was decreased following high flat composition treatment.③PAI-1,t-PA and vWF can be used as molecular markers for vascular endothelial cell injury in distinguishing hyperlipemia in rats. PartⅡEffect of hypertension on vWF,PAI-1 and t-PA in ratsObjective:To observe the time course effect of hypertension on the plasma levels of von willebrand Factor(vWF)and PAl-1 and t-PA in rats and compare the changes among them in order to find one or several highly sensitive and specific marker(s)for vascular endothelium injury on different stages of EH,which will guide the clinical diagnosis and therapeutics of EH.Methods:30 male spontaneously hypertensive rats(SHR)weighting about(205±21)g were taken as EH groups.All rats in EH groups were divided into EH gradeⅠgroup(140 mmHg≤SBP＜160 mmHg, n=10),EH gradeⅡgroup(160 mmHg≤SBP＜180 mmHg,n=10)and EH gradeⅢgroup(SBP≥180 mmHg,n=10)according to their systolic pressure.At the meantime,10 male Sprague-dawley rats were taken as control group.When reach the setting time,the rats were sacrificed and the blood plasma were separated and the levels of the blood plasma TM, PAl-1,t-PA and vWF were detected by ELISA assay and statistical analyses were performed.Meanwhile,the pathological sections of the rats aorta arteriae were prepared to observe the endothelial injury degree..Results:①No lesions were observed in aortic endothelium in rats of all groups using optical microscope②Compared with the control group, the plasma levels of vWF and PAI-1 in EH gradeⅠ,ⅡandⅢgroups were elevated significantly(p＜0.01),while the amount of t-PA were decreased significantly(p＜0.01).③The correlation between the systolic pressure of essential hypertension and vWF,PAl-1,t-PA were at a high level of significance(r=0.911,0.962 and -0.935,p＜0.01)Conclusion:①The plasma levels of vWF and PAI-1 of spontaneously hypertensive rats(SHR)were increased dramatically,- while the amount of t-PA were decreased significantly.②The plasma levels of vWF,PAI-1 were correlated with the systolic pressure of the rats,while t-PA were negatively correlated with the systolic pressure of the rats. They can be used as indicators for the vascular endothelial injury or dysfunction in SHR. PartⅢEffect of radiation on vWF,PAI-1 and t-PA in ratsObjective:To identify the changes of plasma levels of von willebrand Factor(vWF),PAl-1 and t-PA in rats with vascular endothelium injury caused by different doses of radiation and compare the difference among them in order to find one or several highly sensitive and specific marker(s)for vascular endothelium injury at different stages of radiation injury,which will guide the clinical diagnosis and therapeutics of radiation injury.Methods:40 male Sprague-dawley rats weighting about 207±23 g were randomly divided into control group(n=10),radiation groupⅠ(n=10),radiation groupⅡ(n=10)and radiation groupⅢ(n=10).The radiation dosage for each group was 0 Gy,4 Gy,8 Gy and16 Gy respectively.The rats were sacrificed after radiation treatment for 24 h and the blood plasma were separated and the blood plasma levels of TM, PAl-1,t-PA and vWF were detected by ELISA assay and statistics were performed to evaluate the significance.Meanwhile,the pathological sections of the rats aorta arteriae were prepared to observe the endothelial injury degree.Results:①obvious lesions were observed in aortic endothelium in rats from both of control group and radiation groupⅠusing optical microscope.The aortic endothelium of radiation groupⅡrats were swollen and some of them were vacuole-like degeneration and desquamate The aortic endothelium of radiationⅢgroup rats were swollen and most of them were vacuole-like degeneration and desquamate.②Compared with the control group,The plasma levelds of vWF and PAI-1 from radiation group were elevated significantly(p＜0.01),while the plasma level of t-PA from of radiation group were decreased significantly(p＜0.01).③The correlation between the degree of the endothelial injury or dysfunction caused by radiation injury and vWF,PAl-1,t-PA were at a high level of significance(r=0.941, 0.933 and -0.903,p＜0.01)Conclusion:①Vascular endothelial injury or dysfunction were able to be observed following in radiation injury;The vascular endothelial injury or dysfunction was aggravated with the increased intensity of radiation injury②Radiation injury can increase the plasma levels of vWF, PAI-1 and decrease the plasma level of t-PA in rats.The plasma levels of vWF,PAI-1 and t-PA can reflect the vascular endothelial injury or dysfunction in radiation injury and can be used as molecular markers for of vascular endothelial cell injury or dysfunction after radiation injury.③The plasma levels of vWF,PAI-1 in rats were positively related to the degree endothelial injury or dysfunction after in radiation injury,while the plasma level of t-PA was negatively correlated to it.④The plasma levels of vWF,PAI-1 and t-PA can be used as molecular markers for vascular endothelial cell injury or dysfunction caused by radiation injury in rats.