Impact Of Microbubble Excited Ultrasound Cavitation On Prostate

Background:Benign prostate hyperplasia (BPH) is the common disease in the male elders. The incidence could be 50% in the male over 50 and could be 90% in the males over 80. BPH induced to the difficult to urinate, which impact on the quality of life seriously and damage the bladder and renal function.the treatment of BPH is short of the utility and intraumatic methods. At present,various kinds of methods of hot ablation and electrotomy,which is majority investigation and clinical application.however, all of methods on prostate is still the traumatic occlusion and complication.for instance, UA are blockaged by necrotic tissue,which happened to the retention of urine, bleeding, anischuria and infection. accordingly, it is extremely to research the utility and intraumatic methods to treatment BPH.Cavitation is another major nonthermal effect of ultrasound. It happens mainly with mechanical effects like shock wave, microstream, etc. The bioeffects of cavitation might include increased cell-membrane permeability (sonoporation), microvascular rupture and hemorrhage. This study is designed to investigate the mechanical damage of prostate by using ultrasound (US) excited microbubble (MB) cavitation, a potential new therapeutic method based on our previous study of cavitation.Objectives:1. To explore the possibility of prostate damage by US cavitation: two impact factors of ultrasound and microbubble were investigated in the cavitational damage of animal prostate by using gross, microscopy and ultramicroscopy.2. On the microvascular permeability of prostate: quantitative analysis of Evans blue dye as a tracer to estimate the changes of microvascular permeabiblity.3. Apoptosis of prostate. The apoptosis of prostate epithelial cells was assessed by the TUNEL. Methods:The first part1. Animal groups30 male New Zealand white rabbits were randomly divided into the US, the MB, and the US+MB groups.2. On the microvascular permeabilityThere were 5 male New Zealand white rabbits in each group. After anesthetized, the prostates of rabbits were surgically exposed behind spermatophore. The prostates were insonated through the spermatophores from the front, followed by intravenous injection of 2% Evans Blue dye (50mg/kg) and microbubbles (0.1ml/kg). The US group got only the same US exposure and the MB received only MB injection. Then the animal circulation was rinsing by heparin saline from aorta abdominalis. After the prostate harvested, Evans blue was extracted with formylamine for the permeability under different conditions.3. PathologyThere were 5 male New Zealand white rabbits in each group. The procedure was almost the same except no EB injection and no circulation rinsing. Then the prostates were surgical removed and were sent to microscopy and ultramicroscopy.4. ApoptosisThe apoptosis of prostate was estimated by counting the apoptosis index (AI) of every group by using the TUNEL method.The second part1. Animal groups 15 dogs were randomly divided into three groups for the factors of US+MB(n=9), US(n=3) and MB(n=3).2. After anesthetized with abdominal injection of phenobarbital at 1ml/kg, the prostates were surgically exposed and insonated 10 min directly by the US device, followed by intravenous injection of microbubbles suspension (0.1ml/kg). The US and the MB were treated as same as the first part. After the treatment, all prostates were immediately removed for further inspection.3. PathologyAll of the prostates were resected into 4mm slices for gross inspection. The US impacted sites were cut into related pieces, fixed and were sent to microscopy and ultramicoscopy.Results:The first partAccording to the regression equation (y=12.569X+0.120) made by the standard EB solution using optical density, the average EB concentration of the US+MB group (23.6±2.9μg/g) was much higher than that of the US (6.7±0.3μg/g) and the MB (6.2±0.3μg/g) group (P<0.01).Grossly, the prostates were significantly stained blue in the US+MB group, but no staining were found in the other two groups. Under microscopic examination, the glandular epithelial cells appeared to be in normal cubic shape, lined in tight, and there were no significant changes in prostatic tissues in the US and the MB groups. In the US+MB group, there were slightly dilatation of glandular cavities and disorganized epithelium, Massive eosinophilic staining was found in glandular cavities.Under the electronic microscopy, some disrupted cell apparatus and discontinuity of microvascular wall were found. No significant changes in the MB and the US group but some swollen mitochondria.TUNELThe average AI of the MB, the US and the US+MB group were 3.92±6.04%, 8.18±4.29% and 23.31±3.64% respectively. The AI of the US+MB was markly higher than other two groups (P<0.01). There was no significant AI change between the MB and the US group.The Second PartGrossly, severe hemorrhage and hematoma appeared to be the black stained region with clear or blurred boundary in the sections of the US+MB group. The prostates of the other two groups appeared to be in normal color but only minute petechia from operation.The hemorrhage and hematoma were proved in the microscopic examination together with ruptured vessel wall and disorganization of epithelium. No significant changes of the prostatic tissues were found in the US and the MB group.Under the electronic microscope, there were ruptured desmosomes and red blood cell leakage found in the US+MB group. Conclusion:1. US excited microbubble cavitation could significantly increase the vascular permeability of the prostate of rabbits, using EB as the tracer.2. US excited microbubble cavitation could significantly induce the of apoptosis of prostate epithelium.3. US excited microbubble cavitation could significantly make mechanical damage of dog prostate.