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Paclitaxel-Carrying Liposome Microbubbles Combining With Low-Frequency Ultrasound Inhibits Neointimal Hyperplasia In A Rabbit Iliac Balloon Injury Model

Posted on:2013-01-18Degree:MasterType:Thesis
Country:ChinaCandidate:J GuoFull Text:PDF
GTID:2234330374977972Subject:Academy of Pediatrics
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OBJECTIVETo establish the model of iliac artery stenosis in young New Zealandrabbit by balloon expansion,and to analysis the value of ultrasoundtechnology in the evaluation of the model of iliac artery stenosis comparedwith the test results of pathology;To evaluate the effect ofpaclitaxel-carrying liposome microbubbles (PLM) combining withlow-frequency ultrasound on intervention vascular reconstruction;Toexplore the parameters of the low-frequency ultrasound on interveningvascular reconstruction,and to evaluate the effects on the liver and kidneyfunction in young rabbits by irradiating with different low-frequencyultrasound parameters.METHODS①70rabbits,aged (60±15) days,were randomly divided intooperated group, sham-operated group,and the nomal group.The vascularendothelial of the rabbits ’iliac artery in the operated group was injuried with balloon expansion through femeral artery. In sham-operated group, therabbits ’ femoral artery were exposed only.The lumen diameter,tunicaintima thickness and related hemodynamic parameters were calculated bythe ultrasound each week after the operation respectively.The stenosis ratehave been calculated,and compared with the pathology result.②25young New Zealand rabbits,with iliac stenosis by balloonexpansion through femeral artery,were randomly divided into5groups:group A:paclitaxel-carrying liposome microbubbles combining withlow-frequency focused ultrasound group,group B:liposome microbubblescombining with low-frequency focused ultrasound,group C:paclitaxelcombining with low-frequency focused ultrasound group,groupD:low-frequency focused ultrasound group,group E:blank controlgroup.All of the treatment were received after modeling3weeks.Taking thevascular after modeling4weeks.The area of lumen,lining endothelium andtunica media of the iliac artery was measured by HE Staining and ElasticTissue Staining,and the proliferation of the smooth muscle cell wasobserved by immunohistochemistry.③30Young New Zealand rabbits,aged (60±15) days,were randomlydivided into normal group,operation group and intervention group.Establishthe iliac artery stenosis model by balloon dilatation,and intervene the modelby PLM combining with different intensity and frequency low-frequencyultrasound3weeks later.The lumen area and tunica intima area were measured after1week of the intervention.The liver function and kidneyfunction were tested in all the group.RESULTS①The vascular cavity in the operation group was narrower than that in thenomal group after1week of the operation(stenosis rate as13.43%).Therewas a significant correlation between the stenosis rates calculated byultrasound and pathological after2weeks,3weeks and4weeks of theoperation (P<0.05).The tunica intima thickness was increased obviouslyin the operation group.The change of the flow velocity was consistent withthe change of the lumen area.The resistance index and the diastolic tosystolic velocity ratio were in contrast with the flow velocity and the lumenarea.There was no obvious statistical significance between thesham-operated group,and the nomal group (P>0.05).②The vascular structures reconstruction with the elastic fiberhyperplasia in the lining layer was observed obviously after3weeks of thesurgery.The intima area and the tunica media area were the largest in groupE (P<0.05).The lumen area was largest but the intima area and the tunicamedia area were the lowest in group A (P<0.05).The ratio of the intimaarea and tunica media area were reduced after the intervention (P<0.05),especially in group A (P<0.05).In group A,the positive cells wassignificantly Less than the other intervention groups (P<0.05).③In the operation group,the tunica intima area was magnified compared with normal group,when the stenosis rate was (80.22±6.7)%,with cells Disarranged,which was different from that in the nomalgroup (P<0.05).In the intervention groups,part of the intima wasthickened,with membrane cells arranged.The lumen area was enlarged inall the intervention groups (P<0.001),when the tunica intima area weredecreased(P<0.001)and the stenosis rate were reduced (P<0.001),butwas still narrower than the nomal group (P<0.05).The effect was obviousin the intervention group by irradiation conditions with the moderateintensity (1MHz,0.5W/cm2), in which the lumen area was largger thanany other group, and with the minimum tunica intima area (P<0.05),andthe stenosis rate was (16.17±10.45)%.CONCLUSIONSThe model of iliac artery stenosis in young New Zealand rabbits canbe established by balloon expansion through femeral artery,and beevaluated by high frequency vascellum ultrasound imaging technologynoninvasivly and dynamicly,which was consistent with pathologytesting;The hyperplasia of intima-media membrane was reduced by PLMcombining with low-frequency focused ultrasound,which can be used onthe intervention of vascular reconstruction;The vascular reconstruction canbe intervented by different parameters of the low-frequencyultrasound,especially in the intervention group by irradiation conditionswith the moderate intensity (1MHz,0.5W/cm2),without any significant side effects on the liver and kidney function.
Keywords/Search Tags:artery reconstruction, Young New Zealand rabbit, low-frequency ultrasound, paclitaxel, microbubbles
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