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The Yiqihuoxue Compound Of Rabbit Carotid Artery Balloon Injury Restenosis After Preventive And Therapeutic Effects Of Experimental Research

Posted on:2010-02-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:H W LiuFull Text:PDF
GTID:1114360278480997Subject:Chinese medical science
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Purpose:Observe the effects of Yiqihuoxuefufang(YQHXFF) on the model of vascular restenosis established by balloon injury of carotid arteries in cholesterol rabbits.Investigate and discuss the mechanisms of YQHXFF preventing restenosis on intima hyperplasia and vascular remodeling after balloon withdrawal injury of rabbit carotid artery.Material and method:The formulation of YQHXFF were consisted of Huangqi 25g, danshen 30g,renshen 30g,honghua 15g,yimucao 25g,sanqi 5g,chuanxiong 15g. Passing some steps such as boiling and so on.Craft to make into the powder. Their final concentrations were each gram contain the creude drug 4.8 grams.Choose 32 New Zealand white rabbits,weighing from(2.5±0.5)kg were used. Rabbits were randomly divided into 2 groups after adaptive feed for one week. Including control group and ballone injury group.The control group were fed with normal food,and the ballone injury group were fed with high cholesterol food.Then performed with balloon injury on carotid artery.After 4 weeks,the ballone injury group rabbits were randomly divided into 3 groups.Including model group,simvastatin group and YQHXFF group.The operation group was fed with drugs separately,group of simvastatin:fed simvastatin 5 mg/kg/day,group of YQHXFF: fed YQHXFF 1g creude drug/kg/day.The ballone injury group were fed with high cholesterol food and the control group were fed with normal food in whole times. Content:①Observed the pathologic alter and the pathomarphological changes under light and electron microscope at 8 weekends;②Measureses the level of TG,TC,HDL- C and LDL- C of plasma at 0,4 and 8 weekend;③Use spectrophotometer to measure the nitric oxide(NO) contents at 8 weekend in plasma;④Use the ELISA method to examination the level of endothelin-1(ET-I) at 8 weekend in plasma;⑤Adopt ELISA method to exam the each rabbit the level of tissue-type plasminogen activator(t-PA) and plasminogen activator inhibitor type-1(PAI-1) in plasma at 0 week,4 weekend and 8 weekend;⑥Measures the level of tissue factor(TF) in plasma at 0 week,4 weekend and 8 weekend with ELISA method;⑦The Nuclear factor kappa B(NF-κB) and vascular cell adhesion molecule-1(VCAM-1) mRNA were measured with reverse transcription polymerise chain reaction(RT-PCR) at 8 weekend;⑧At 8th weekend,the NF-κB and VCAM-1 pro were measured with immunohistochemistry;⑨At 8th weekend,the level of platelet derived growth factor(PDGF) and matrix metalloproteinase-2(MMP-2) mRNA were measured with RT-PCR.Results:1.Compared the YQHXFF intervention group with those in the model group,The intimal hyperplasia is markedly lighten.2.Compared the model group,the level of TC,TG,LDL- C in the YQHXff group and those in the simvastatin group were lower.At 8 weekend,the levle of TC,TG, LDL-C of YQHXFF group were decreased 53.36%,31%and 60%,increased the level of HDL-C 160%.simvastatin is better than YQHXFF at lowering the level of TC and LDL- C.(P<0.05) but YQHXFF is good at increase the level of HDL-C.There is noobvious differences in decreasing TG between the YQHXGG group and simvastatin group.(P>0.05).3.YQHXFF can increase the level of NO in blood and decrease the level of ET-1, is advantageous to the instauration NO/ET-1 enzyme equilibrium,have the function of protection the endothelial cell.①4 weeks after the ballon injury, the model group's plasma NO content is(46.004±3.125)μmol/ mL,much lower than control group(112.930±2.227)μmol/ mL(p<0.01).The plasma NO content in simvastatin and YQHXFF group is(77.001±5.902)μmol/mL and(123.373±7.180)μmol/mL,much higher than the model group(p<0.01);Among them,the YQHXFF group plasma NO level is higher than the simvastatin group.(p<0.01);②By ELISA method,the plasma ET-1 have a higher level in modelgroup.Compared with the model group,the level of plasma ET-1 in simvastatin group and YQHXFF group were lower obvious.(P<0.05),but the simvastatin group and YQHXFF group's plasma ET-1 level did not show the difference.(P>0.05) 4.YQHXFF can keep belance in PAS,decrease the expression of TF.①At 8 weekend, the YQHXFF and simvastatin group the level of t-PA in plasma is(0.238±0.061) IU/mL and(0.169±0.089)IU/mL,comparing the model group(0.103±0.076)IU/mL the difference obviously(P<0.05),the level of t-PA in YQHXFF group is much higher than that in the simvastatin group.(P<0.05);②By ELISA method,the plasma PAI-1 have a higher level in the model group.Compared with the model group,the level of plasma PAI-1 in simvastatin group and YQHXFF group were lower obvious.(P<0.05),but the simvastatin group and YQHXFF group's plasma PAT-1 level did not show the difference.(P>0.05);③At weekend,the plasma and carotid arteries TF have a higher level in the modelgroup.Compared with the model group, the level of TF in simvastatin group and YQHXFF group were lower obviously. (P<0.05),but the simvastatin group and YQHXFF group's TF level did not show the difference.(P>0.05)5.YQHXFF can inhibit.the expression of NF-κB and VCAM-1:①At 8 weekend,the NF-κB and VCAM-1 mRNA expression is higher in modelgroup than that in the other two groups by RT-PCR.Their expression in the YQHHFF and simvastatin group is no obvious differences;②By immunohistochemistry,the NF-κB and VCAM-1 pro expression is higher in model group than that in the other two groups.Their expression in the YQHHFF and simvastatin group is not show obvious differences.6.YQHXFF can inhibit the expression of PDGF and MMP-2:At 8th weekend,the PDGF and MMP-2 mRNA expression is higher in model group than that in the other two groups by RT-PCR.Their expression in the YQHHFF and simvastatin group is no obvious differences.Conclusion:1.YQHXFF can lighten the intimal hyperplasia after PTCA2.YQHXFF has effect of modulating blood lipid,and it can decrease the level of TC,LDL-C,TG and increasing the level of HDL-C,is good at rectify the disturbance of lipid metabolism.3.Both YQHXFF and simvastatin have there superiority on prevent restenosis after PTCA,but YQHXFF can avoid the side effect of simvastatin effectively.Such as rhabdomyolysis etc.4.YQHXFF inhibits restenosis atfer PTCA by complicated structure and various mechanisms.
Keywords/Search Tags:YQHXFF, PTCA, restenosis, ballone injury, atherosclerosis, simvastatin
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