低功率超声联合微泡照影剂对慢性细菌性前列腺炎治疗效应的研究

发布时间：2018-05-15 00:07

本文选题：肠杆菌 + 大鼠模型　；参考：《第三军医大学》2014年硕士论文

【摘要】：研究背景：慢性细菌性前列腺炎常见于成年男性，是发病率较高的感染性疾病。目前针对慢性细菌性前列腺炎治疗以口服抗生素为主，但治疗效果并不令人满意。其原因可能是血前列腺屏障（blood prostate barrier, BPB）的存在所致。血前列腺屏障的存在使得前列腺免受有害因素的侵袭，但同时也使得药物难以进入前列腺腔隙。因此，增加前列腺药物通透性可能是影响前列腺炎治疗效果的关键。超声空化效应的发现可能为这一问题找到了解决方案，当微泡照影剂受到超声辐照时，发生内爆，其产生的物理射流可使细胞膜“打孔”，暂时性的提高细胞膜通透性。本研究拟使用低功率超声联合微泡照影剂开放大鼠血前列腺屏障，在大鼠慢性细菌性前列腺炎模型上起到促进疗效作用。第一部分：低浓度大肠埃希菌注射法制作大鼠慢性细菌性前列腺炎模型目的：寻找合适的大肠埃希菌浓度，，建立符合慢性前列腺炎病理特征的大鼠模型。方法：选用健康的成年远交群（Sprague Dawley，SD）大鼠36只，随机等分为对照组、低浓度组、高浓度组。采用前列腺内直接注射的方式建模，对照组注射生理盐水，低浓度组及高浓度组分别注射浓度为1.5×108CFU/ml、3×109CFU/ml的大肠埃希菌液，建模4周后处死大鼠，在光镜下观察大鼠前列腺的病理变化。结果：空白对照组大鼠前列腺无炎性表现，高浓度组大鼠前列腺炎症表现为急性化脓性感染，且死亡率较高，低浓度组大鼠前列腺在显微镜下成慢性增生性炎症，符合慢性前列腺炎病理表现。结论：采用浓度为1.5×108CFU/ml的大肠埃希菌液直接注射的方法成功建立大鼠模型。第二部分：低功率超声联合微泡照影剂开放血前列腺屏障的初步探讨目的：使用伊文思蓝（Evans Blue，EB）作为示踪剂，探讨低功率超声联合微泡造影剂对血前列腺屏障的开放作用。方法：选取成年雄性SD大鼠48只,随机分为4组。分别为对照组、EB组、即刻组、延迟组，均给予相同剂量的超声辐照5min，对照组给予生理盐水，伊文思蓝组按体重50mg/kg剂量给于伊文思蓝，微泡组以0.1ml/kg剂量给于微泡造影剂，即刻组尾静脉注射伊文思蓝-微泡混合液后前列腺局部间歇辐照5min，延迟组尾静脉注射微泡后用超声治疗仪前列腺局部间歇辐照5min，辐照结束后30分钟给予EB。实验结束后取前列腺组织观察，并检测前列腺内EB的浓度。结果：EB组前列腺组织中药物浓度较对照组高（P0.05），即刻组前列腺组织中药物浓度较EB组以及延迟组高（P0.05）。结论：低功率超声联合微泡造影剂可以开放血前列腺屏障，提高前列腺组织药物浓度，且有一定的时效性。第三部分：低功率超声联合微泡照影剂对慢性细菌性前列腺炎的疗效研究目的：在慢性细菌性前列腺炎大鼠模型上使用超声微泡开放血前列腺屏障，增加前列腺内药物浓度，达到治疗目的。方法：选已建立慢性细菌性前列腺炎模型的SD大鼠48只，随机分为4组。分为对照组、微泡组、药物组、药物+微泡组，均给与超声辐照5min，对照组按体重0.1ml/kg注射生理盐水，单纯微泡组按体重注射0.1ml/kg微泡造影剂，单纯药物组按体重0.1mg/kg给予左氧氟沙星，单纯药物+微泡组给予0.1ml/kg左氧氟沙星微泡混合液。每间隔1天行一次治疗，疗程8天。实验结束后观测大鼠前列腺病理组织变化并进行病理评分。结果：与药物组及微泡组相比，药物+微泡组前列腺腺体内炎性细胞侵润腺体明显减少，且有统计学意义（P＜0.05）。结论：低功率超声联合微泡造影剂能够增加腺体内部药物浓度，有效治疗腺体内感染。
[Abstract]:Background: chronic bacterial prostatitis is common in adult males and is an infectious disease with high incidence. Oral antibiotics are mainly used in the treatment of chronic bacterial prostatitis, but the effect is not satisfactory. The reason may be the presence of blood prostate barrier (BPB). The presence of the barrier makes the prostate free from harmful factors, but it also makes it difficult to enter the prostate lacunar. Therefore, increasing the permeability of the prostate may be the key to the effect of prostatitis.
The discovery of ultrasonic cavitation may find a solution to this problem. When the microbubble illuminant is irradiated by ultrasound, the internal detonation occurs. The physical jets can make the cell membrane "punch" and temporarily improve the permeability of the cell membrane. It plays an important role in the treatment of chronic bacterial prostatitis in rats.
Part I: a rat model of chronic bacterial prostatitis was injected with low concentration of Escherichia coli.
Objective: to find the suitable concentration of Escherichia coli and establish a rat model that accords with the pathological characteristics of chronic prostatitis.
Methods: 36 Sprague Dawley (SD) rats were randomly divided into the control group, the low concentration group and the high concentration group. The control group was modeled by the direct injection of the prostate, the control group was injected with saline, the low concentration group and the high concentration group were injected with the concentration of 1.5 x 108CFU/ml, 3 * 109CFU/ml of Escherichia coli, modeling 4. After death, rats were sacrificed and the pathological changes of the prostate were observed under light microscope.
Results: the prostatitis of the rats in the blank control group was not inflammatory. The prostatitis in the high concentration group showed acute suppurative infection and the mortality was higher. The prostate in the low concentration group was chronic hyperplastic inflammation under the microscope, which was in line with the pathological manifestation of chronic prostatitis.
Conclusion: the rat model was successfully established by direct injection of Escherichia coli with a concentration of 1.5 * 108CFU/ml.
The second part: preliminary study of opening the blood prostate barrier with low power ultrasound combined with microbubbles.
Objective: To explore the effect of low power ultrasound combined with microbubbles on the blood prostate barrier by using Evans Blue (EB) as a tracer.
Methods: 48 adult male SD rats were randomly divided into 4 groups, the control group, the EB group, the immediate group, the delayed group, the same dose of ultrasound irradiated 5min, the control group was given the saline, the Evans Blue Group
The dose of 50mg/kg was given to Evans blue, and the microbubble group was given a microbubble contrast agent at a dose of 0.1ml/kg, and immediately after the injection of Evans blue microbubble mixture in the tail vein, the prostate was irradiated locally intermittently after the injection of 5min. After the delayed injection of microbubbles in the tail vein, the local intermittent radiography of the prostate was 5min, and the EB. experimental knot was given 30 minutes after the end of irradiation. The prostate tissues were observed and the concentration of EB in the prostate was detected.
Results: the concentration of drug in prostate tissue of group EB was higher than that of control group (P0.05), and the concentration of drug in prostatic tissue was higher than that in group EB and delayed group (P0.05).
Conclusion: low power ultrasound combined with microbubbles can open the blood prostate barrier and improve the concentration of prostate tissue, and it has a certain timeliness.
The third part: the effect of low power ultrasound combined with microbubbles on chronic bacterial prostatitis.
Objective: to use ultrasound microbubbles to open blood prostate barrier in chronic bacterial prostatitis rats, and increase the concentration of drugs in the prostate to achieve the goal of treatment.
Methods: 48 SD rats were selected to establish a chronic bacterial prostatitis model. They were divided into 4 groups randomly. They were divided into control group, microbubble group, drug group, drug + microbubble group and irradiated 5min by ultrasonic irradiation. The control group was injected with physiological saline by weight 0.1ml/kg. The simple microbubble group was injected with 0.1ml/kg microbubble contrast agent by weight, and the pure drug group was 0.1mg/kg body weight 0.1mg/kg Levofloxacin was given, a single drug + microbubble group was given 0.1ml/kg levofloxacin microbubble mixture. A treatment was performed every 1 days at a interval of 8 days. After the experiment, the pathological changes of the prostate were observed and the pathological scores were observed.
Results: compared with the drug group and the microbubble group, the inflammatory cells infiltration glands in the prostate gland of the drug + microbubble group were significantly reduced, and there was statistical significance (P < 0.05).
Conclusion: low power ultrasound combined with microbubble contrast agent can increase drug concentration in glands and effectively treat intra gland infection.

【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R697.33

【参考文献】