| Background:Prostatic diseases were common in male. It's about 70% of men above 50 years old suffering from anguish of prostatic diseases. As we found in a long term clinical practice, prostatic tissues may exist some certain constructions to shield harmful factors in blood vessels and prevent drugs enter prostatic tissues.At present researchers consider that the fibromuscular interstitial tissue,lipid of glandular epithelium and etc are main structures of blood-prostate barrier. It may prevent drugs enter prostatic tissue and cause great waste in common treatment. Our main subject is to find out a specific and harmless method to open blood-prostate barrier.Objective:To prove the feasibility of noninvasive defining parameters ultround can open the blood-prostate barrier in presence of ultrasound contrast agent.To find out the condition and phase of blood-prostate barrier induced low-frequency pulsed ultrasonic energy plus ultrasond contrast agent.And to explore the impacts of different conditions upon apoptosis expression in prostate cells.Methods:40 ripe male newzealand white rabbits were divided into two groups randomly.Each group contained 20 rabbits. Rabbits in group 1 were divided into four small groups:①US,②MB,③US+MB,④Control(CO). Sliced off abdomen and exposed spermatophores in front of prostate. 2%Evans Blue were injected into ear veins, and then injected microbubbles and made ultrasonic wave irradiated the prostate through spermatophores at the same time.Some time later made aorta abdominalis perfused and removed the prostate. Observed the effusion of Evans Blue in the Evans Blue fluorescence microscopy method. Detected the peak value of absorbance through a full wavelength scan with Du-800UV/Visible spectrophotometer and concluded a formula between EB concentration and OD. Extracted Evans Blue in the prostate with formylamine and examined changes of permeability of blood-prostate barrier in different conditions.Rabbits in group 2 were divided into four groups as well as in group 1, and the processing methods were similar with group 1 except injecting Evans Blue, and perfusing heparinized nomal saline either. Took prostatectomy and observed the opening condition of blood-prostate barrier after HE staining. Observed the Ultrastructural changes under the electron microscope and estimated apoptosis index (AI) with TUNEL method. Results:Group1:Red fluorescence of Evans Blue could be found all in group US,MB and US+MB. After staining with haematoxylin, red fluorescence was recognised both in fibromuscular tissues and gland cavities in group US+MB ,nevertheless red fluorescence could only be found in fibromuscular tissues in group US and MB.We found that the EB solution made a peak value of absorbance while the wavelength was 625nm. The formula we regressed was y=12.569X+0.120(axis y for EB concentration, axis x for OD). The average concentration of Evans Blue in group US+MB (10.385±0.790μg/g) was obvious different from group US(6.706±0.312μg/g),MB (6.258±0.352μg/g) and CO(6.099±0.508μg/g) , it was markly higher than other three groups (P<0.01). There was no significant difference among the other three groups in Evans Blue average concentration (P>0.05).Group2:There was no significant change in prostatic tissues among group US,MB and CO under the microscope. Cytoplasm and nucleoli were stained equably, cells of glandular epithelium were intact and formed orderly. Glandular cavities in these two group were change very slightly. Glandular epithelium cells of Group US+MB were organized mussily under the optical microscope, and there was a mass of eosinophilic liquid in some glandular cavities. The average AI of group MB was 6.420±2.454%,5.800±1.241% in group CO,30.780±4.634% in group US and 42.636±2.430%in group US+MB. AIs in group US and group US+MB were markly higher than other two groups(P<0.01). AI of group US+MB was markly higher than in group US.There was no significant change in AI between group MB and CO. There were a great deal of secretory granules both in gland cells and glandular cavities in group MB and group CO ,and swollen mitochondria could be found under the eletron microscope. On the other hand , secretory granules reduced markedly in group US, tight junctions among gland cells were opened. A great deal of cells were necrotic and disaggregating in group US+MB.Conclusion:1.Pulsed ultrasonic energy may cause cavitation effect and open blood-prostate barriers.2.Cavitation effect that caused by ultrasonic energy could be strengthened markedly while ultrasound contrast agents exist.3.The main mechanisms of opening blood-prostate barriers:①ultrasound cause cavitation effects of microbubbles and make vessel wall full of sound pores;②endothelial cells shrink after suffering from mechanical influence that caused by shock waves and tight junctions are exploded.4.Pulsed ultrasonic energy may increase the expression of apoptosis in cavitation way. This capability may be strengthened while microbubbles exist.
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