“尿道滴白”的原因探讨
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摘要
背景及目的
慢性前列腺炎是泌尿外科最常见而又充满困惑的一种疾病,多发于成年男性,发病率约为9-16%,患者占泌尿外科门诊病人的25-33%,复发率为25%-50%。大约50%的男性在一生中的不同时期曾有过慢性前列腺炎症状。该病常表现为局部疼痛,排尿异常、尿道滴白,性功能障碍以及全身症状如精神症状等,可导致男性不育,是50岁以下男性人群泌尿外科就诊的最常见原因之一。目前,由于其病因复杂,症状多变,病程迁延,缺乏诊断的金标准和有效的治疗方法,无论是泌尿外科医生,还是患者对其治疗效果均不满意。
近年来国内外对慢性前列腺炎的研究取得了较大的进展,由于前列腺炎症状的复杂多变,许多学者对其产生机制也做了深入的研究,但截止目前,仍无法用单一机制对前列腺炎复杂多变的临床现象进行解释,而且各学者之间意见也不尽一致。
“尿道滴白”是泌尿外科门诊患者常见的症状之一,多数学者认为“尿道滴白”为慢性前列腺炎患者前列腺液分泌过多或排除不畅时“满则溢”所致,因而又被称为“前列腺溢液”。然而持此观点者缺乏相应的临床和动物实验支持,且部分慢性前列腺炎患者给予持续性的药物治疗后前列腺炎症好转或消失(EPS中白细胞和/或脓细胞减少、消失)而尿道滴白的临床症状却无明显好转或持续存在。因此,尿道滴白是否另有来源?尿道腺分布于尿道粘膜下层,具有粘液的高分泌功能,且受神经和周围理化因素的影响,是否存在某种神经机制导致尿道腺分泌功能异常而产生尿道滴白?现有文献未见相关的研究报道。
现已有不少学者发现在内脏器官与内脏器官之间、内脏器官与躯体某些部位间存在神经反射,通过一个器官或躯体某部位的刺激可影响与之相应的另一器官功能,其中与前列腺炎有关的神经反射也有报道。我们前期研究显示,当前列腺受到炎症刺激后可通过神经反射引起多种会阴及盆腔脏器功能改变,如尿频,疼痛,前列腺炎患者尿道滴白是否也是这一组盆腔脏器神经反射所致?本课题从以下三方面入手展开研究:1.尿道滴白液是否是前列腺液?课题通过尿道滴白患者尿道分泌物与前列腺液进行对比研究;2.前列腺炎会否使尿道腺体分泌功能改变;3,尿道腺体的植物神经受体分布;通过研究,有望证实前列腺炎导致尿道滴白症状的神经机制,并为从神经调控入手治疗尿道滴白提供理论依据。
方法:
1.对有“尿道滴白”症状的患者留取其尿道分泌物及前列腺液作酸性磷酸酶活性检测,结果采用统计学方法测定“尿道滴白”患者尿道分泌物与前列腺液中酸性磷酸酶活性及其95%可信区间是否一致,明确尿道滴白是否来自前列腺液
2.采用健康的成年雄性SD大鼠为研究对象,分别用弗氏完全佐剂和0.9%的生理盐水构建前列腺炎模型和模型对照,造模成功后分别检测尿道腺单细胞粘液的面积、直径和光密度,探讨前列腺炎对尿道腺粘液产生的作用;进一步对前列腺炎造模成功后大鼠和对照组大鼠行电刺激,收集尿道腺的分泌液,测定比较其分泌量及分泌的蛋白浓度,探讨前列腺炎对尿道腺粘液分泌的作用。
3.神经受体拮抗剂阻滞相应的受体后给予电刺激,收集尿道腺的分泌液分别测定其分泌量及分泌的蛋白浓度,同时,检测刺激后的尿道腺单细胞残余粘液的面积、直径、光密度。以探讨支配尿道腺分泌的神经受体及其在炎症等伤害刺激下的变化。
主要结果:
1.对有“尿道滴白”症状的患者进行临床调查结果是:纳入调查的31例病例中,有1例患者的尿道分泌物和前列腺液酸性磷酸酶活性近似,可能为前列腺液溢出所致,占调查总数的3.2%;余患者尿道分泌物与前列腺液酸性磷酸酶活性差异显著,且其95%可信区间无重叠,由此得出,尿道滴白液体主要不是来源于前列腺液,而是另有来源。
2.大鼠在前列腺炎造模成功后,与对照组相比,尿道腺单细胞粘液的面积、直径和光密度结果均差异非常显著。进一步给予电刺激,收集并比较尿道腺分泌的粘液量和粘液蛋白浓度,结果差异显著。证实前列腺受到伤害性刺激时可以引起尿道腺合成和分泌功能的改变,为尿道滴白症状的产生机制和来源途径提供动物实验依据。
3.在前列腺炎组大鼠中,药物阻滞后,电刺激前列腺后外侧的神经血管束,收集并比较尿道腺分泌的液体量,结果提示M受体受阻滞后,其分泌量显著下降,且差异显著,但分泌的蛋白浓度却显著上升,具体机制有待进一步实验研究。进一步比较尿道腺残余的粘液面积、直径、光密度,结果M受体受刺激组残余量最低且差异显著。证实支配前列腺炎模型大鼠尿道腺分泌的神经受体是M受体。在对照组大鼠中,采用上述方法进行实验,结果证实M受体也是主要的支配神经受体。为尿道滴白症状的药物治疗提供理论依据。
结论及展望:
1.慢性前列腺炎患者的尿道滴白主要不是来源于前列腺液,而是另有来源。
2.慢性前列腺炎所致的尿道腺体分泌功能增强是尿道滴白的主要原因。
3.调控尿道腺体分泌的植物神经受体为M受体,且调控作用受炎症等伤害性刺激的影响而易化。神经调控,对抗植物神经受体治疗是减少尿道滴白的可选方法,应进行深入的临床和基础研究。
Background and objectives:
Chronic prostatitis is the most common and confusing urological disease. Adult males are prone to have prostatitis. The incidence rate of chronic prostatitis is about 9-16%, and accounted for 25-33% of outpatient urological patients and the recurrence rate is 25% to 50%. About 50% men have had symptoms of chronic prostatitis in different times in their lives. The disease usually manifests local pain, abnormal urination, urethra secretions, sexual dysfunction, and systemic symptoms such as psychiatric symptoms and can lead to male infertility, too. Meanwhile, as one of the most common cause, the male patients under 50 years old see a doctor for it. At present, because of its complex causes, variety of symptoms, a long course of disease, and lack of diagnostic gold standard and effective treatment, whether urology doctors or patients were dissatisfied with their treatment.
In recent years, great progress has been made on studies of chronic prostatitis at home and abroad. Due to the complexity of prostatitis symptom, many scholars have done deep research on their mechanism. Someone has made some progress, but can not use a single mechanism to explain the clinical phenomenon of prostatitis. Until now, scholars have various views.
Urethra secretions is a common symptom of chronic prostatitis, and most scholars believe that Urethra secretions for the excessive secretion of the prostate in patients with chronic prostatitis or because of prostatic fluid discharge poor, but have not clinical investigation and animal experiments to support their view. Symptoms of some patients with chronic prostatitis improved or disappeared because of drug adherence, but symptoms of urethral secretion did not significantly improve, therefore, the urethral secretion is from the other glands? Urethral glands are in the urethral submucosa with mucus secretion high, and are secreted by the nerves or by the surrounding physical and chemical factors. The existence of a neural mechanism leading to urethral gland dysfunction caused urethral secretion? None of the existing literature related to its further reports.
So far, many scholars have found that there are some neural reflexes existing among mutual viscera organs and between viscera organs and some part in the body. Stimulation on a viscera organ or some part of its body could affect another organs’related function. There are some reports of these neural reflexes related to prostatitis, too. Our preliminary study shows that a variety of perineal and pelvic organ dysfunction such as frequent urination and pain are achieved by reflex when the prostate can be stimulated by inflammation. So symptoms of urethral secretion are also due to pelvic organ reflex? The study of the subject will do research from the following three areas: 1, Whether Urethral discharge is from a prostate? 2, Can urethral gland secretion make changes by prostatitis? 3, How does the autonomic nerve receptors of urethral glands distribute? This study will concentrate on the neural mechanism of urethral secretion after chronic Prostatitis and suggest a potential neuromodulational therapy for urethral secretion of chronic Prostatitis.
Methods:
1, keep the urethral secretions and prostatic fluid from the patients who have urethral secretion Symptom for detecting acid phosphatase activity. Then, determine specific components of urethral secretions and prostatic fluid with t test, so as to confirm whether urethral secretion is from the prostate.
2, Use healthy adult male SD rats as experimental animals, injected Freund's complete adjuvant in prostate of animal models manufacturing Prostatitis at the same time, and injected 0.9% saline in prostate of another group rats as control. Then through detecting single-cell mucus area, diameter and optical density of their urathral gland, so as to probing prostatitis on the role of urethral glands produce mucus. Do electrical stimulation to the prostatitis rats and control rats, then collect the secretion of their urethral gland. At last, determine and compare its secretion and protein concentration so as to probing prostatitis on the role of urethral glands produce mucus
3, After neural antagonists completely blocking the corresponding receptor,electrical stimulusing the urethral gland, collect the secretion of urethral gland, then determine their fluid secretion and the secreted protein concentration. At the same time, respectively test their single-cell mucus area, diameter, optical density, so as to explore the neural receptors which control urethral gland secretions and their changes under noxious stimulation.
Results:
1,The laboratory test result is that in the 31 surveyed cases, only one patient whose acid phosphatase activity of urethral discharge and prostatic is the same. This phenomenon shows urethral secretions are from the prostate, but this only accounts for 3.2% of the total patients investigated. The others’urethral secretions and prostatic fluid acid phosphatase activity are significantly different. 95% confidence interval of acid phosphatase activity of patients who have urethral secretions symptom and 95% confidence interval of acid phosphatase of Prostatitis is no overlap. The result confirms that the urethral secretions is not a prostate fluid overflow.
2. Prostatitis rats made by Freund's complete adjuvant injected into the prostate Analog noxious stimulation. Compared with the controlled group, a single cell mucous area, diameter and optical density of urethral gland were very significant different. And do electrical stimulation on the prostatitis rats and control rats to collect the secretion of their urethral gland and determine and compare its secretion and its protein concentration. Results are significantly different. When prostate suffer the noxious stimulation, urethral glands and other organs functional change. These instructions create mechanisms and sources. Urethra secretions provide basis for animal experiments
3. In prostatitis rats, nerve receptors had completely blocked by drug when given to electrical stimulation of the neurovascular bundle which after the lateral prostate. Urethral gland secretion measurement results suggest that M receptors block behind, and its secretion is significantly decreased, but the secretion mucus protein concentration increased significantly, which specific mechanisms need to be further studied. Micro-urethral gland is measured residual mucus area, diameter, and optical density and compared. The residual amount of M receptor-stimulated group is the least. The result Confirmed M receptors is urethral gland of prostatitis rat play a dominant roles. In the control rats, using the above method, experimental results confirm that M receptor is still the main nerve receptors. This experiment provides a theoretical basis for drug treatment about the symptoms of urethral secretion
Conclusion and Outlook:
1. Urethral secretions of patients with chronic prostatitis are not primarily derived from the prostatic fluid, but are from another gland.
2. Chronic prostatitis caused by increased secretion of the urethral gland is the main reason of urethral secretion
3. M receptor is the major nerve receptors which dominate urethral gland secretion, and will change more efficiently because of such noxious stimulation by inflammatory. Against autonomic receptors is the alternative method for reducing urinaral secretion, and should be carried out in further clinical and basic research
慢性前列腺炎是泌尿外科最常见而又充满困惑的一种疾病,多发于成年男性,发病率约为9-16%,患者占泌尿外科门诊病人的25-33%,复发率为25%-50%。大约50%的男性在一生中的不同时期曾有过慢性前列腺炎症状。该病常表现为局部疼痛,排尿异常、尿道滴白,性功能障碍以及全身症状如精神症状等,可导致男性不育,是50岁以下男性人群泌尿外科就诊的最常见原因之一。目前,由于其病因复杂,症状多变,病程迁延,缺乏诊断的金标准和有效的治疗方法,无论是泌尿外科医生,还是患者对其治疗效果均不满意。
近年来国内外对慢性前列腺炎的研究取得了较大的进展,由于前列腺炎症状的复杂多变,许多学者对其产生机制也做了深入的研究,但截止目前,仍无法用单一机制对前列腺炎复杂多变的临床现象进行解释,而且各学者之间意见也不尽一致。
“尿道滴白”是泌尿外科门诊患者常见的症状之一,多数学者认为“尿道滴白”为慢性前列腺炎患者前列腺液分泌过多或排除不畅时“满则溢”所致,因而又被称为“前列腺溢液”。然而持此观点者缺乏相应的临床和动物实验支持,且部分慢性前列腺炎患者给予持续性的药物治疗后前列腺炎症好转或消失(EPS中白细胞和/或脓细胞减少、消失)而尿道滴白的临床症状却无明显好转或持续存在。因此,尿道滴白是否另有来源?尿道腺分布于尿道粘膜下层,具有粘液的高分泌功能,且受神经和周围理化因素的影响,是否存在某种神经机制导致尿道腺分泌功能异常而产生尿道滴白?现有文献未见相关的研究报道。
现已有不少学者发现在内脏器官与内脏器官之间、内脏器官与躯体某些部位间存在神经反射,通过一个器官或躯体某部位的刺激可影响与之相应的另一器官功能,其中与前列腺炎有关的神经反射也有报道。我们前期研究显示,当前列腺受到炎症刺激后可通过神经反射引起多种会阴及盆腔脏器功能改变,如尿频,疼痛,前列腺炎患者尿道滴白是否也是这一组盆腔脏器神经反射所致?本课题从以下三方面入手展开研究:1.尿道滴白液是否是前列腺液?课题通过尿道滴白患者尿道分泌物与前列腺液进行对比研究;2.前列腺炎会否使尿道腺体分泌功能改变;3,尿道腺体的植物神经受体分布;通过研究,有望证实前列腺炎导致尿道滴白症状的神经机制,并为从神经调控入手治疗尿道滴白提供理论依据。
方法:
1.对有“尿道滴白”症状的患者留取其尿道分泌物及前列腺液作酸性磷酸酶活性检测,结果采用统计学方法测定“尿道滴白”患者尿道分泌物与前列腺液中酸性磷酸酶活性及其95%可信区间是否一致,明确尿道滴白是否来自前列腺液
2.采用健康的成年雄性SD大鼠为研究对象,分别用弗氏完全佐剂和0.9%的生理盐水构建前列腺炎模型和模型对照,造模成功后分别检测尿道腺单细胞粘液的面积、直径和光密度,探讨前列腺炎对尿道腺粘液产生的作用;进一步对前列腺炎造模成功后大鼠和对照组大鼠行电刺激,收集尿道腺的分泌液,测定比较其分泌量及分泌的蛋白浓度,探讨前列腺炎对尿道腺粘液分泌的作用。
3.神经受体拮抗剂阻滞相应的受体后给予电刺激,收集尿道腺的分泌液分别测定其分泌量及分泌的蛋白浓度,同时,检测刺激后的尿道腺单细胞残余粘液的面积、直径、光密度。以探讨支配尿道腺分泌的神经受体及其在炎症等伤害刺激下的变化。
主要结果:
1.对有“尿道滴白”症状的患者进行临床调查结果是:纳入调查的31例病例中,有1例患者的尿道分泌物和前列腺液酸性磷酸酶活性近似,可能为前列腺液溢出所致,占调查总数的3.2%;余患者尿道分泌物与前列腺液酸性磷酸酶活性差异显著,且其95%可信区间无重叠,由此得出,尿道滴白液体主要不是来源于前列腺液,而是另有来源。
2.大鼠在前列腺炎造模成功后,与对照组相比,尿道腺单细胞粘液的面积、直径和光密度结果均差异非常显著。进一步给予电刺激,收集并比较尿道腺分泌的粘液量和粘液蛋白浓度,结果差异显著。证实前列腺受到伤害性刺激时可以引起尿道腺合成和分泌功能的改变,为尿道滴白症状的产生机制和来源途径提供动物实验依据。
3.在前列腺炎组大鼠中,药物阻滞后,电刺激前列腺后外侧的神经血管束,收集并比较尿道腺分泌的液体量,结果提示M受体受阻滞后,其分泌量显著下降,且差异显著,但分泌的蛋白浓度却显著上升,具体机制有待进一步实验研究。进一步比较尿道腺残余的粘液面积、直径、光密度,结果M受体受刺激组残余量最低且差异显著。证实支配前列腺炎模型大鼠尿道腺分泌的神经受体是M受体。在对照组大鼠中,采用上述方法进行实验,结果证实M受体也是主要的支配神经受体。为尿道滴白症状的药物治疗提供理论依据。
结论及展望:
1.慢性前列腺炎患者的尿道滴白主要不是来源于前列腺液,而是另有来源。
2.慢性前列腺炎所致的尿道腺体分泌功能增强是尿道滴白的主要原因。
3.调控尿道腺体分泌的植物神经受体为M受体,且调控作用受炎症等伤害性刺激的影响而易化。神经调控,对抗植物神经受体治疗是减少尿道滴白的可选方法,应进行深入的临床和基础研究。
Background and objectives:
Chronic prostatitis is the most common and confusing urological disease. Adult males are prone to have prostatitis. The incidence rate of chronic prostatitis is about 9-16%, and accounted for 25-33% of outpatient urological patients and the recurrence rate is 25% to 50%. About 50% men have had symptoms of chronic prostatitis in different times in their lives. The disease usually manifests local pain, abnormal urination, urethra secretions, sexual dysfunction, and systemic symptoms such as psychiatric symptoms and can lead to male infertility, too. Meanwhile, as one of the most common cause, the male patients under 50 years old see a doctor for it. At present, because of its complex causes, variety of symptoms, a long course of disease, and lack of diagnostic gold standard and effective treatment, whether urology doctors or patients were dissatisfied with their treatment.
In recent years, great progress has been made on studies of chronic prostatitis at home and abroad. Due to the complexity of prostatitis symptom, many scholars have done deep research on their mechanism. Someone has made some progress, but can not use a single mechanism to explain the clinical phenomenon of prostatitis. Until now, scholars have various views.
Urethra secretions is a common symptom of chronic prostatitis, and most scholars believe that Urethra secretions for the excessive secretion of the prostate in patients with chronic prostatitis or because of prostatic fluid discharge poor, but have not clinical investigation and animal experiments to support their view. Symptoms of some patients with chronic prostatitis improved or disappeared because of drug adherence, but symptoms of urethral secretion did not significantly improve, therefore, the urethral secretion is from the other glands? Urethral glands are in the urethral submucosa with mucus secretion high, and are secreted by the nerves or by the surrounding physical and chemical factors. The existence of a neural mechanism leading to urethral gland dysfunction caused urethral secretion? None of the existing literature related to its further reports.
So far, many scholars have found that there are some neural reflexes existing among mutual viscera organs and between viscera organs and some part in the body. Stimulation on a viscera organ or some part of its body could affect another organs’related function. There are some reports of these neural reflexes related to prostatitis, too. Our preliminary study shows that a variety of perineal and pelvic organ dysfunction such as frequent urination and pain are achieved by reflex when the prostate can be stimulated by inflammation. So symptoms of urethral secretion are also due to pelvic organ reflex? The study of the subject will do research from the following three areas: 1, Whether Urethral discharge is from a prostate? 2, Can urethral gland secretion make changes by prostatitis? 3, How does the autonomic nerve receptors of urethral glands distribute? This study will concentrate on the neural mechanism of urethral secretion after chronic Prostatitis and suggest a potential neuromodulational therapy for urethral secretion of chronic Prostatitis.
Methods:
1, keep the urethral secretions and prostatic fluid from the patients who have urethral secretion Symptom for detecting acid phosphatase activity. Then, determine specific components of urethral secretions and prostatic fluid with t test, so as to confirm whether urethral secretion is from the prostate.
2, Use healthy adult male SD rats as experimental animals, injected Freund's complete adjuvant in prostate of animal models manufacturing Prostatitis at the same time, and injected 0.9% saline in prostate of another group rats as control. Then through detecting single-cell mucus area, diameter and optical density of their urathral gland, so as to probing prostatitis on the role of urethral glands produce mucus. Do electrical stimulation to the prostatitis rats and control rats, then collect the secretion of their urethral gland. At last, determine and compare its secretion and protein concentration so as to probing prostatitis on the role of urethral glands produce mucus
3, After neural antagonists completely blocking the corresponding receptor,electrical stimulusing the urethral gland, collect the secretion of urethral gland, then determine their fluid secretion and the secreted protein concentration. At the same time, respectively test their single-cell mucus area, diameter, optical density, so as to explore the neural receptors which control urethral gland secretions and their changes under noxious stimulation.
Results:
1,The laboratory test result is that in the 31 surveyed cases, only one patient whose acid phosphatase activity of urethral discharge and prostatic is the same. This phenomenon shows urethral secretions are from the prostate, but this only accounts for 3.2% of the total patients investigated. The others’urethral secretions and prostatic fluid acid phosphatase activity are significantly different. 95% confidence interval of acid phosphatase activity of patients who have urethral secretions symptom and 95% confidence interval of acid phosphatase of Prostatitis is no overlap. The result confirms that the urethral secretions is not a prostate fluid overflow.
2. Prostatitis rats made by Freund's complete adjuvant injected into the prostate Analog noxious stimulation. Compared with the controlled group, a single cell mucous area, diameter and optical density of urethral gland were very significant different. And do electrical stimulation on the prostatitis rats and control rats to collect the secretion of their urethral gland and determine and compare its secretion and its protein concentration. Results are significantly different. When prostate suffer the noxious stimulation, urethral glands and other organs functional change. These instructions create mechanisms and sources. Urethra secretions provide basis for animal experiments
3. In prostatitis rats, nerve receptors had completely blocked by drug when given to electrical stimulation of the neurovascular bundle which after the lateral prostate. Urethral gland secretion measurement results suggest that M receptors block behind, and its secretion is significantly decreased, but the secretion mucus protein concentration increased significantly, which specific mechanisms need to be further studied. Micro-urethral gland is measured residual mucus area, diameter, and optical density and compared. The residual amount of M receptor-stimulated group is the least. The result Confirmed M receptors is urethral gland of prostatitis rat play a dominant roles. In the control rats, using the above method, experimental results confirm that M receptor is still the main nerve receptors. This experiment provides a theoretical basis for drug treatment about the symptoms of urethral secretion
Conclusion and Outlook:
1. Urethral secretions of patients with chronic prostatitis are not primarily derived from the prostatic fluid, but are from another gland.
2. Chronic prostatitis caused by increased secretion of the urethral gland is the main reason of urethral secretion
3. M receptor is the major nerve receptors which dominate urethral gland secretion, and will change more efficiently because of such noxious stimulation by inflammatory. Against autonomic receptors is the alternative method for reducing urinaral secretion, and should be carried out in further clinical and basic research
引文
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