本文選題：超聲 + 微泡��； 參考：《川北醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:1.模擬體外流動(dòng)模型,觀察超聲波輻照聯(lián)合微泡在血栓溶解中的作用,評估超聲波輻照增強(qiáng)血栓溶解效果。2.在體外實(shí)驗(yàn)中對比自制脂質(zhì)微泡(microbubbles,MBs)與Sono Vue的血栓溶解差異,觀察不同類型微泡對血栓溶解的影響。3.在體外實(shí)驗(yàn)中對比觀測37℃與41℃不同環(huán)境溫度的血栓溶解差異,了解溫度對體外血栓溶解的影響。4.在體外實(shí)驗(yàn)中對比新鮮血栓與回縮血凝塊的血栓溶解差異,了解超聲波輻照聯(lián)合微泡在不同栓齡血栓中的溶解作用。方法:1.脂質(zhì)微泡的制備:二棕櫚酰磷脂酰膽堿(DPPC)、聚乙二醇二硬脂酰磷脂酰乙胺(DSPE-PEG)、甘油、全氟丙烷,通過機(jī)械震蕩法制備脂質(zhì)微泡。2.血栓制備:1新鮮血栓:用枸櫞酸真空采血管抽取健康志愿者全血,氯化鈣溶液促進(jìn)血液凝固,放入37℃溫浴箱溫浴3h后,將血栓放入4℃冰箱儲(chǔ)存3h。2回縮血凝塊:用枸櫞酸真空采血管抽取健康志愿者全血,氯化鈣溶液促進(jìn)血液凝固,37℃溫浴箱溫浴3h后,在4℃冰箱儲(chǔ)存7d,7d后取出試管,將半透明的血清從血凝塊中分離,以獲得穩(wěn)定的回縮血凝塊。3.體外循環(huán)裝置:由密閉模擬血管管道、恒溫水浴箱、微量蠕動(dòng)泵、藥物注入通道組成。整個(gè)實(shí)驗(yàn)過程密閉管道置于恒溫水浴中,循環(huán)管道流速控制在4.5ml/s,超聲波輻照探頭置于血栓垂直正上方5cm處固定。4.實(shí)驗(yàn)分組:按超聲波輻照、微泡、尿激酶、環(huán)境溫度以及血栓栓齡的不同組合,隨機(jī)分為1個(gè)對照組、6個(gè)實(shí)驗(yàn)組,每組10個(gè)樣本,超聲波輻照參數(shù)統(tǒng)一設(shè)定為頻率1MHz,強(qiáng)度2w/cm2,占空比50%。A組:超聲波假輻照20min,生理鹽水2ml,水浴溫度37℃,新鮮血栓。B組:超聲波輻照20min,MBs 1ml,生理鹽水1ml,水浴溫度37℃,新鮮血栓。C組:超聲波輻照20min,尿激酶1ml,生理鹽水1ml,水浴溫度37℃,新鮮血栓。D組:超聲波輻照20min,MBs 1ml,尿激酶1ml,水浴溫度37℃,新鮮血栓。E組:超聲波輻照20min,Sono Vue 1ml,尿激酶1ml,水浴溫度37℃,新鮮血栓。F組:超聲波輻照20min,MBs 1ml,尿激酶1ml,水浴溫度41℃,新鮮血栓。G組:超聲波輻照20min,MBs 1ml,尿激酶1ml,水浴溫度37℃,回縮血凝塊。5.應(yīng)用西門子ACUSON SC2000超聲診斷儀和L9-1超聲探頭測量狹窄率和血栓面積。觀察指標(biāo):血栓溶解前后的血栓重量損失率、血栓溶解前后體外循環(huán)管道的血栓放置部位管腔狹窄率、血栓溶解前后的血栓最大長軸切面面積減少率。6.統(tǒng)計(jì)學(xué)處理:七組的測量數(shù)據(jù)經(jīng)正態(tài)性檢驗(yàn)均服從正態(tài)分布(P0.05),方差同質(zhì)性檢驗(yàn),方差齊(P0.05),七組的各變量均為連續(xù)性數(shù)值變量,各組變量以均值±標(biāo)準(zhǔn)差()表示,七組間整體比較采用單因素方差分析,評價(jià)七組血栓溶解效果的整體趨勢及差異;兩兩間比較采用LSD-t分析,進(jìn)行超聲波輻照聯(lián)合微泡、微泡類型、溫度、栓齡分別對血栓溶解作用的分析。均以P0.05為具有統(tǒng)計(jì)學(xué)意義。所有數(shù)據(jù)均采用SPSS 21.0統(tǒng)計(jì)軟件進(jìn)行分析。結(jié)果:1.七組血栓溶解前后重量損失率、面積減少率及管腔狹窄率改變,各組間整體比較,差異具有顯著統(tǒng)計(jì)學(xué)意義(P0.01)。2.A組與B組:血栓溶解前后重量損失率、面積減少率差異具有顯著統(tǒng)計(jì)學(xué)意義(P0.01),重量損失率從3%增加到10%,同比增高233%,面積減少率從2%增加到7%,同比增高250%,管腔狹窄率的比較無顯著統(tǒng)計(jì)學(xué)差異(P0.05)。3.C組與D組:血栓溶解前后重量損失率、面積減少率差異具有顯著統(tǒng)計(jì)學(xué)意義(P0.01),重量損失率從15%增加到16%,同比增高7%,面積減少率從10%增加到14%,同比增高40%,管腔狹窄率的比較無顯著統(tǒng)計(jì)學(xué)差異(P0.05)。4.D組與E組:血栓溶解前后重量損失率、面積減少率及管腔狹窄率差異均具有顯著統(tǒng)計(jì)學(xué)意義(P0.01),重量損失率從16%增加到21%,同比增高31%,面積減少率從14%增加到25%,同比增高79%,管腔狹窄率從6%增加到12%,同比增高100%。5.D組與F組:血栓溶解前后重量損失率、面積減少率及管腔狹窄率差異均具有顯著統(tǒng)計(jì)學(xué)意義(P0.01),重量損失率從16%增加到29%,同比增高81%,面積減少率從14%增加到31%,同比增高121%,管腔狹窄率從6%增加到13%,同比增高117%。6.G組與A組:血栓溶解前后重量損失率、面積減少率及管腔狹窄率無顯著統(tǒng)計(jì)學(xué)差異(P0.05)。7.G組與D組:血栓溶解前后重量損失率、面積減少率及管腔狹窄率差異均具有顯著統(tǒng)計(jì)學(xué)意義(P0.01),重量損失率從2%增加到16%,同比增高700%,面積減少率從2%增加到14%,同比增高600%,管腔狹窄率從3%增加到6%,同比增高200%。結(jié)論:1.本實(shí)驗(yàn)初步證明,在體外模擬血管血液流動(dòng)模型中,超聲波輻照(f=1MHz,P=2.0w/cm2,占空比50%)聯(lián)合微泡可促進(jìn)血栓溶解。2.Sono Vue與自制脂質(zhì)微泡均能增強(qiáng)血栓溶解,Sono Vue作用更為顯著。3.體外血栓溶解中,溫度的改變影響新鮮血栓溶解,溫度升高可顯著增強(qiáng)血栓溶解。4.微泡介導(dǎo)的超聲增強(qiáng)尿激酶溶栓,受栓齡的影響明顯,不能有效促進(jìn)回縮血凝塊溶解。
[Abstract]:Objective: 1. simulate the flow model in vitro, observe the effect of ultrasonic irradiation combined with microbubbles in thrombolysis and evaluate the difference of thrombolysis between microbubbles, MBs and Sono Vue by ultrasound irradiation enhanced thrombolytic effect in vitro, and observe the effect of different types of microbubbles on thrombolysis in vitro, and the effect of.3. on the thrombolysis in vitro is true in vitro. The difference of thrombolysis between 37 and 41 C was observed and the effect of temperature on thrombolytic dissolution in vitro.4. was compared in vitro to compare the difference of thrombolysis between fresh thrombus and retracted blood clot, and to understand the dissolution of ultrasonic irradiation combined with microbubbles in thrombolytic thrombus. Method: preparation of 1. lipid microbubbles: two Palmiyl phosphatidylcholine (DPPC), polyethylene glycol two stearyl phosphatidylethylamine (DSPE-PEG), glycerin, perfluoropropane, preparation of lipid microbubble.2. thrombus by mechanical shock: 1 fresh thrombus: extract healthy volunteers from healthy volunteers with citric acid vacuum blood vessel, calcium chloride solution to promote blood coagulation, and put blood in a warm bath for 3H in a warm bath box at 37 C The thrombus was placed in the refrigerator at 4 C to store 3h.2 retracted blood clot: the whole blood of healthy volunteers was extracted with citric acid vacuum extraction blood vessel, calcium chloride solution was used to promote blood coagulation, and after a warm bath of 37 centigrade temperature bath for 3h, 7d was stored in the refrigerator at 4 C, and the test tube was taken out after 7d to separate the semitransparent serum from the blood clot to obtain a stable.3. cardiopulmonary bypass device for retracted blood clot: The closed pipe, constant temperature water bath, microperistaltic pump, and drug injection channel were made up. The closed pipe was placed in a constant temperature water bath in the whole experimental process. The flow velocity of the circulating pipe was controlled at 4.5ml/s. The ultrasonic probe was placed at the vertical 5cm above the thrombus and fixed in the.4. experiment. The temperature was irradiated by ultrasound, microbubbles, urokinase, and ambient temperature. The different combinations of thrombus age were randomly divided into 1 control groups, 6 experimental groups, 10 samples in each group, and the ultrasonic irradiation parameters were set as frequency 1MHz, intensity 2w/cm2, duty ratio 50%.A group: ultrasonic false irradiation 20min, physiological saline 2ml, water bath temperature 37, and fresh blood suppository.B group: ultrasonic irradiation 20min, MBs 1ml, normal saline 1ml, water bath temperature Degree 37 C, fresh thrombus.C group: ultrasound irradiation of 20min, urokinase 1ml, physiological saline 1ml, water bath temperature 37,.D group of fresh thrombus: ultrasonic irradiation 20min, MBs 1ml, urokinase 1ml, water bath temperature 37 C, fresh thrombus.E group: ultrasonic irradiation 20min, urokinase, water bath temperature 37, fresh thrombus group: ultrasonic irradiation group: ultrasonic irradiation group 1ml, urokinase 1ml, water bath temperature 41 C, fresh thrombus.G group: ultrasound irradiation of 20min, MBs 1ml, urokinase 1ml, water bath temperature 37, and retracted blood clot.5. using SIEMENS ACUSON SC2000 ultrasound diagnostic instrument and L9-1 ultrasonic probe to measure the stenosis rate and thrombus area. The stenosis rate of the thrombus placement of the extracorporeal circulation pipeline and the reduction rate of the maximum axial section area of thrombus before and after thrombolytic dissolution were.6. statistically treated: the measured data of the seven groups were all subject to normal distribution (P0.05), the variance homogeneity test, Fang Chaqi (P0.05), and the variables of the seven groups were continuous numerical variables, each of the variables By means of mean mean standard deviation (), the overall trend and difference of seven groups of thrombolytic effects were evaluated by single factor variance analysis in the seven groups. The analysis of ultrasonic irradiation combined with microbubbles, microbubbles type, temperature and thrombolytic age in the seven groups was statistically significant for the analysis of thrombolytic effect of thrombolysis in the seven groups. All data were analyzed with SPSS 21 statistical software. Results: 1. seven groups of thrombolytic weight loss rate, area reduction rate and lumen stenosis rate were changed in seven groups. The difference between groups was statistically significant (P0.01).2.A group and B group: the weight loss rate before and after thrombolysis and the difference of area reduction rate were statistically significant Meaning (P0.01), the weight loss rate increased from 3% to 10%, increased by 233%, the area reduction rate increased from 2% to 7%, increased 250% from the same period, and there was no significant difference in the stenosis rate (P0.05).3.C group and D group: the weight loss rate before and after thrombolysis, the difference in area reduction rate had significant statistical significance (P0.01), and the weight loss rate increased from 15% to 15%. The increase was 16%, up 7%, the reduction rate of area increased from 10% to 14%, increased by 40%, and there was no significant statistical difference (P0.05) between group.4.D and E: the weight loss rate, area reduction rate and lumen stenosis rate before and after thrombolysis were statistically significant (P0.01), the weight loss rate increased from 16% to 21%, and increased from year to year. The high 31%, the area reduction rate increased from 14% to 25%, the increase of 79%, the stenosis rate of the lumen increased from 6% to 12%, the increase of the 100%.5.D group and the F group: the difference of the weight loss, the area reduction rate and the stenosis rate of the lumen before and after thrombolysis (P0.01), the weight loss rate from 16% to 29%, the increase of 81% and the reduction rate of the area compared to the same period. From 14% to 31%, the increase was 121%, the stenosis rate of the lumen increased from 6% to 13%, the 117%.6.G group and the A group were higher than the same period. There was no significant difference between the weight loss rate, the area reduction rate and the stenosis rate of the lumen before and after thrombolysis (P0.05) group.7.G and D group: the weight loss rate, the area reduction rate and the narrowing rate of the lumen before and after thrombolysis were both significant With statistical significance (P0.01), the weight loss rate increased from 2% to 16%, increased by 700%, the reduction rate of area increased from 2% to 14%, increased 600% from year to year, the stenosis rate of the lumen increased from 3% to 6%, and increased by 200%. conclusion: 1. in this experiment, in vitro simulated blood flow model, ultrasonic irradiation (f=1MHz, P=2.0w/cm2, duty ratio 50%) combined with f=1MHz, P=2.0w/cm2 and 50%) The microbubbles could promote thrombolytic dissolution of thrombolytic.2.Sono Vue and self-made lipid microbubbles, and the effect of Sono Vue was more significant in thrombolysis in.3. in vitro. The change of temperature affects the dissolution of fresh thrombus. The increase of temperature can significantly enhance thrombolytic dissolved.4. microbubbles mediated ultrasound enhanced urokinase thrombolysis. The effect of thrombolytic age is obvious. The effect promotes the retracted blood clot to dissolve.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R54;R743

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