Low Frequency Ultrasound Combined With Targeted Microbubbles In Thrombolytic Therapy Of Acute DVT In Rabbits

Objective:Using multimodal ultrasound to evaluate the model of venous thrombosis in the lower cavity of rabbit,and studying the biological effects of low-power focused ultrasound at different irradiation times,the optimal irradiation time was screened,and the treatment effect of single-cloned microfoules of single-cloned antibodies carrying tumor necrosis factor-α(TNF-α)was observed on the basis of urine kinase thrombosis.Methods:1.Japanese large-eared white rabbit 30,divided into two groups,thrombosis model group 15,low-frequency ultrasound group 15.Thrombosis model group:After the establishment of IVC thrombus model,3 doctors used different examination methods to observe the situation of 15 rabbits,Group A used 2D ultrasound examination,group B used 2D+CDFI examination,group C(multimodal ultrasound group)used 2D+CDFI+CEUS examination,and measured the extent of thrombosis.After the examination,the rabbits were killed to obtain the pathological results.Low-frequency ultrasonic irradiation group:The normal rabbit IVC segment is irradiated with low frequency ultrasound,which is divided into a,b,c 3 groups according to the irradiation time,each group of 5,group a:20min irradiated,group b:irradiated 35min,c group:irradiated 50min,Once a day for 3 days.Each group was treated for three days,once a day,and the rabbit was executed after the last treatment.2.Treatment of venous thrombosis in the lower cavity of rabbits:The 40 successful thrombosis rabbits were divided into 4 groups,us group,US+UK group,US+UK+MBN group,and US+UK+MBT group,each group of 10.US group:Use low-power focused ultrasonic irradiation.US+UK group:Use low-power focused ultrasonic irradiation+Intravenous urine kinase.US+UK+MBN group:Use low-power focused ultrasonic irradiation+Intravenous urine kinase+Intravenous non-Targeted microbubble.US+UK+MBT group:Use low-power focused ultrasonic irradiation+Intravenous urine kinase+ Intravenous TNF-α antibody targeted microbubble.3.Before molding,after molding,after irradiation to take the rabbit outer vein blood test clotting four,ELISA method to detect the content of TNF-α and D-dimer,rabbit under the cavity vein tissue HE staining,MSB staining examination,after irradiation using CEUS to observe the cavity vein retransformation,and calculate the retranscing rate of each group.Results:1.Multimodal ultrasound has the highest detection rate in the diagnosis of acute thrombosis,and CEUS has the most accurate detection range for blood clots.2.The biological effects of ultrasonic irradiation:Group a(irradiated 20min):rabbit Inferior vena cava endothorn cell morphology clear,flat arrangement,smooth pipe wall,clear structure;Group b(irradiated 35min):endothorn cells fall off,arrange disorders,and the mid-membrane structure is slightly edema;Group c(irradiated 50min):endothorn cells fall off,the endometrium breaks,red blood cells and inflammatory cells seep out of the inner membrane,tube wall structure disorders;3.Detection indexes of peripheral bloodComparison among groups:after irradiation,PT,APTT and TT in US+UK group,US+UK+MBN group and US+UK+MBT group were longer than those in US group(P<0.05),FIB and D-dimer contents were lower than those in US group(P<0.05),TNF-α content in US+UK+MBT group was significantly lower than that in US group,US+UK group and US+UK+MBN group(P<0.05).Pair comparison before modeling,after modeling and after irradiation in each group:The PT of US+UK group,US+UK+MBN group and US+UK+MBT group after irradiation was longer than that before modeling(P<0.05),APTT and TT in US+UK group,US+UK+MBN group and US+UK+MBT group were longer than before and after modeling(P<0.05),and the contents of Fib and D-dimer were lower than before and after modeling(P<0.05).After irradiation,TNF-α content decreased significantly only in the US+UK+MBT group,but increased in the other three groups as time went on.4.Evaluation of vascular patencyThe recanalization rate was 10%in US group,40%in US+UK group,60%in US+UK+MBN group and 70%in US+UK+MBT group.Fisher exact probability analysis showed that the recanalization rate of US+UK group,US+UK+MBN group and US+UK+MBT group was significantly higher than that of us group(P<0.05).The recanalization rate of US+UK+MBN group and US+UK+MBT group was significantly higher than that of US+UK group(P<0.05),but there was no significant difference between US+UK+MBT group and US+UK+MBN group(P>0.05)Conclusion:1.Multimodal ultrasound can significantly improve the detection rate of thrombosis,and CEUS is convenient and radiation free,which can be used as the"gold standard" for the diagnosis of deep vein thrombosis,and can be used to evaluate the efficacy of thrombosis.2.Low-power focused ultrasound irradiation of the inferior vena cava for 20 minutes showed no obvious damage to the lumen,slight damage to the lumen was observed after 35 minutes of irradiation,and severe damage to the lumen after 50 minutes of irradiation.Therefore,20 minutes of irradiation was selected as the condition for the next treatment of venous thrombosis.3.After the evaluation and analysis of the patency of the thrombus,it was found that the lumen recanalization rate of the US+UK+MBN group and the US+UK+MBT group was the highest,followed by the US+UK group and the US group.4.Low-frequency ultrasound combined with microvesicles and urokinase can significantly improve the dissolution rate of thrombus without increasing the risk of additional bleeding,while targeting microvesicles can not only improve the recanalization rate,but also reduce the inflammatory response of the body,providing a new idea and method for the diagnosis and treatment of thrombus in the future.