本文選題：腸桿菌 + 大鼠模型�。� 參考：《第三軍醫(yī)大學(xué)》2014年碩士論文

【摘要】：研究背景：慢性細(xì)菌性前列腺炎常見于成年男性，是發(fā)病率較高的感染性疾病。目前針對慢性細(xì)菌性前列腺炎治療以口服抗生素為主，但治療效果并不令人滿意。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襲，但同時也使得藥物難以進(jìn)入前列腺腔隙。因此，增加前列腺藥物通透性可能是影響前列腺炎治療效果的關(guān)鍵。 超聲空化效應(yīng)的發(fā)現(xiàn)可能為這一問題找到了解決方案，當(dāng)微泡照影劑受到超聲輻照時，發(fā)生內(nèi)爆，其產(chǎn)生的物理射流可使細(xì)胞膜“打孔”，暫時性的提高細(xì)胞膜通透性。本研究擬使用低功率超聲聯(lián)合微泡照影劑開放大鼠血前列腺屏障，在大鼠慢性細(xì)菌性前列腺炎模型上起到促進(jìn)療效作用。 第一部分：低濃度大腸埃希菌注射法制作大鼠慢性細(xì)菌性前列腺炎模型 目的：尋找合適的大腸埃希菌濃度，，建立符合慢性前列腺炎病理特征的大鼠模型。 方法：選用健康的成年遠(yuǎn)交群（Sprague Dawley，SD）大鼠36只，隨機(jī)等分為對照組、低濃度組、高濃度組。采用前列腺內(nèi)直接注射的方式建模，對照組注射生理鹽水，低濃度組及高濃度組分別注射濃度為1.5×108CFU/ml、3×109CFU/ml的大腸埃希菌液，建模4周后處死大鼠，在光鏡下觀察大鼠前列腺的病理變化。 結(jié)果：空白對照組大鼠前列腺無炎性表現(xiàn)，高濃度組大鼠前列腺炎癥表現(xiàn)為急性化膿性感染，且死亡率較高，低濃度組大鼠前列腺在顯微鏡下成慢性增生性炎癥，符合慢性前列腺炎病理表現(xiàn)。 結(jié)論：采用濃度為1.5×108CFU/ml的大腸埃希菌液直接注射的方法成功建立大鼠模型。 第二部分：低功率超聲聯(lián)合微泡照影劑開放血前列腺屏障的初步探討 目的：使用伊文思藍(lán)（Evans Blue，EB）作為示蹤劑，探討低功率超聲聯(lián)合微泡造影劑對血前列腺屏障的開放作用。 方法：選取成年雄性SD大鼠48只,隨機(jī)分為4組。分別為對照組、EB組、即刻組、延遲組，均給予相同劑量的超聲輻照5min，對照組給予生理鹽水，伊文思藍(lán)組按 體重50mg/kg劑量給于伊文思藍(lán)，微泡組以0.1ml/kg劑量給于微泡造影劑，即刻組尾靜脈注射伊文思藍(lán)-微泡混合液后前列腺局部間歇輻照5min，延遲組尾靜脈注射微泡后用超聲治療儀前列腺局部間歇輻照5min，輻照結(jié)束后30分鐘給予EB。實(shí)驗(yàn)結(jié)束后取前列腺組織觀察，并檢測前列腺內(nèi)EB的濃度。 結(jié)果：EB組前列腺組織中藥物濃度較對照組高（P0.05），即刻組前列腺組織中藥物濃度較EB組以及延遲組高（P0.05）。 結(jié)論：低功率超聲聯(lián)合微泡造影劑可以開放血前列腺屏障，提高前列腺組織藥物濃度，且有一定的時效性。 第三部分：低功率超聲聯(lián)合微泡照影劑對慢性細(xì)菌性前列腺炎的療效研究 目的：在慢性細(xì)菌性前列腺炎大鼠模型上使用超聲微泡開放血前列腺屏障，增加前列腺內(nèi)藥物濃度，達(dá)到治療目的。 方法：選已建立慢性細(xì)菌性前列腺炎模型的SD大鼠48只，隨機(jī)分為4組。分為對照組、微泡組、藥物組、藥物+微泡組，均給與超聲輻照5min，對照組按體重0.1ml/kg注射生理鹽水，單純微泡組按體重注射0.1ml/kg微泡造影劑，單純藥物組按體重0.1mg/kg給予左氧氟沙星，單純藥物+微泡組給予0.1ml/kg左氧氟沙星微泡混合液。每間隔1天行一次治療，療程8天。實(shí)驗(yàn)結(jié)束后觀測大鼠前列腺病理組織變化并進(jìn)行病理評分。 結(jié)果：與藥物組及微泡組相比，藥物+微泡組前列腺腺體內(nèi)炎性細(xì)胞侵潤腺體明顯減少，且有統(tǒng)計(jì)學(xué)意義（P＜0.05）。 結(jié)論：低功率超聲聯(lián)合微泡造影劑能夠增加腺體內(nèi)部藥物濃度，有效治療腺體內(nèi)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.

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R697.33

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