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방광근 수축기전에 관한 실험적 연구

Other Titles
 Experimental study on the contractile mechanism of the urinary bladder 
Issue Date
1977
Description
의학과/박사
Abstract
[한글] 방광은 요(尿)의 저장과 배출에 관여하는 장기이나 방광기능 이상(異常)은 그 영향이 곧 상부요로에 미치게 되므로 임상적 의의는 매우 크다. 대부분의 상부요로 감염이 방광기능부전으로 병발되는 예가 많고 하부요로의 감염도 방광기능 저하로 조직 저항력이 약 화되어 나타나는 수가 적지 않다. 방광의 배뇨활동에 관여하는 주된 운동신경은 골반신경으로 그 충격전파인자는 acetylcholine으로 알려져 있다. 그러나 골반신경자극 또는 nicotine성 신경절흥분약물에 의한 방광수축이 atropine 저항하는 것으로 보아 골반신경의 일부가 비콜린성 (non-cholinergi c)섬유일 가능성을 주장하게 되었고, acetylcholine 이외에 다른 전파인자의 가능성을 모색하였으나 아직도 진성전파인자는 찾지 못하고 있는 실정이다. 또한 배뇨작용에 대한 교감신경인 하복신경의 역할도 확실치 않다. 하복신경을 절단하여도 배뇨자체에는 큰 지장 없고 빈뇨(頻尿)만 초래된다고 보고되고 있다. 최근 방광의 자율신경지배, 각 receptors, 전파인자, 배뇨시 교감 및 부교감신경의 상호 작용에 대한 연구가 적지 않으나 아직도 이론 (異論)이 많다. 이에 본 실험은 수종동물을 사용하여 생체내에서 골반신경자극 및 자율신경계 약물에 대한 방광내압의 변화와 적출 방광근 표본에서 방광근 receptor 태도 및 수축기전을 검색하였다. 실험방법: 흰쥐, 고양이, 개, 토끼 및 인체의 방광에서 dome과 trigone으로부터 1.5cm 정도의 절편표본을 만들었다. 방광근절편의 운동은 force displacement transducer를 통해 Grass polygraph model 7에 묘사하였다. 토끼와 고양이에서는 생체내에서 골반신경자극 및 기타 약물을 적용하여 방광내압의 변화를 관찰하였다. 이상의 실험결과를 요약하면 다음과 같다. 1. 토끼, 개, 흰쥐, 고양이 및 인체의 방광근절편은 자발수축운동을 나타내고 그 수축강도는 동물에 따라 차이가 있었다. 2. Catecholamine적용에 의한 배뇨근 억제반응은 propranolol로 봉쇄되었으며 흰쥐 및 고양이에서는 봉쇄효과 뿐 아니라 수축항진도 초래되었다. 3. Catecholamine적용에 의한 삼각근의 수축항진은 phenoxybenzamine으로 봉쇄되고 이완현상까지도 나타냈으나 이 이완현상은 propranolol 첨가로 소실되었다. 4. 부교감신경계약물 및 신경절흥분약물은 토끼 및 고양이 배뇨근 수축을 항진시키고 대량의 atropine 및 buscopan 투여는 그 효과를 봉쇄하였으나 소량의 atropine에서는 TMA의 효과는 봉쇄되지 않았다. 5. 4℃의 Tyrode액에 2주간 보관한 토끼 방광근절편은 약물 반응에 큰 차이 없고 조직상에도 큰 변화는 없었다. 그러나 개, 고양이 및 인체의 방광근절편은 2일 이상 보존하기 어려웠다. 6. 생체내에서 골반신경자극 및 신경절흥분약물에 대한 방광수축은 atropine으로 부분봉쇄를, hexamethonium으로 완전봉쇄를 나타냈다. 7. Serotonin은 개와 흰쥐 방광근절편에서 예민한 수축항진반응을, prostaglandin E^^2 및 F^^2α는 토끼 방광근절편에 미약한 항진반응을, imipramine은 토끼 방광근절편에 완만간 그러나 오래 지속되는 억제효과를 나타냈다. 이상의 결과로 보아 방광근에 cholinergic receptor는 고르게 분포되고 토끼 및 고양이 신경절에는 nicotinic receptor 이외에 muscarinic receptor가, 개와 흰쥐에는 serotonin receptor가 관여할 것으로 생각된다. Adrenergic receptor는 동물에 따라 근소한 차이 는 있으나 전방광근에 분포되고 배뇨근에는 수축억제 반응을 나타내는 βreceptor가, 삼각근 및 방광경부에는 수축항진 반응을 나타내는 α receptor가 우세하였다. Atropine-resistance현상은 in vivo 및 in vitro에서 볼 수 있어 일부 신경섬유가 noncholinergic일 가능성을 시사해 준다. Experimental Study on the Contractile Mechanism of the Urinary Bladder Hyung Ki Choi Department of Medical Science, The Graduate School, Yonsei University (Directed by Profs. Chong Soon Wang and Sa Suk Hong) A large portion of upper urinary tract infections are usually secondary to dysfunction of the bladder or urinary sphincter. In addition many lower urinary tract infections are directly related to decreased resistance of bladder tissue due to its abnormal bladder function. A knowledge of the mechanism of normal micturition and recognition of the aberrations is essential for accurate diagnosis and appropriate treatment. Though the pelvic nerve is the main motor innervation of the urinary bladder, contraction of the bladder by pelvic nerve stimulation or nicotinic ganglion stimulation is highly resistant to blockade by antimuscarinic agents. Concerning these atropine-resistant phenomena, there are two diametrically opposed points of view. One view insists that acetylcholine is the true transmitter agent and atropine-resistance is caused by the close adherence of motor nerve endings to the individual muscle cell or by a sufficiently high concentrations of acetylcholine released to overcome atropine black. The other is that acetylcholine is not the transmitter agent released at motor nerve endings. Rather, the true agent is unknown. The functional significance of the sympathetic bladder innervation is not clear. From previous and recent experiments it is known that an apparantly normal micturition also takes place in the absence of sympathetic nerves, although the volume is decreased. In sprite of remarkable advances in the fields of neuroanatomy and neuropharmacology, there still remain many controversial debates on the autonomic nerve control of the bladder, receptors, transmitters and the mutual interaction of autonomic nerves in micturition. The present study was designed to determine the contractile mechanism of the urinary bladder, e.g., the character of receptors to autonomic drugs and related agents in vivo and in vitro. Bladder muscle strips about 1.5cm in length were carefully isolated from the dome and trigone of the rat, cat, dog, rabbit and human. They were suspended in a muscle chamber containing 100ml of Tyrode solution maintained at a constant temperature of 38℃. The chamber was aerated with 95% oxygen and 5% carbondioxide bubbling through the bathing fluid by messrs of sintered glass plate at the bottom. The bladder strip was attached to the Grass force displacement transducer and the motility and tonus were recorded on a Grass model 7 polygraph. Being left in fresh Tyrode solution, the bladder strip attained a spontaneous motility and tonus. Then several drugs were added to the muscle chamber and the changes of motility of the strips were observed. In the cat and rabbit changes of intravesical pressure were recorded on a Grass model 7 polygraph by Statham P23 transducer after stimulation of the pelvic nerve and infusion of some drugs in situ. The results obtained were as follows. 1. Spontaneous rhythmic activity was observed in rat, cat, rabbit, dog and human bladder muscle strips. It was noted that there were some species differences in intensity of motility and generally the motility of detrusor strips was active, while the motility of trigone strips was weak and insignificant. 2. The inhibitory response of the detrusor strip to catecholamine was abolished by propranolol. 3. The excitatory response of the trigone strip to catecholamine was abolished and converted to relaxation by pretreatment with phenoxybenzamine and relaxation was abolished by propranolol. 4. In cat and rabbit, the increased contraction responses of detrusor strips were followed by the cholinergic and ganglionic stimulating agents and the effects were abolished by atropine, but the effect of TMA was only partially blocked by atropine. 5. In rabbit detrusor stored at 4℃ Tyrode solution for 2 weeks, there were no significant changes in motility or in histologic findings, but motility was difficult to preserve more than 2 days in detrusor strips of cat, dog and man. 6. Bladder contraction by pelvic nerve stimulation in situ wag partially blocked by atropine and was completely blocked by hexamethonium concomitantly. 7. Serotonin induced a remarkable contraction response in rat and dog detrusor strips. Prostaglandin E^^2 and F^^2α produced delayed and sluggish contractions, while imipramine produced delayed and long-lasting relaxation in rabbit detrusor strips. From the above results, it is suggested that cholinergic receptors are scattered throughout the entire bladder muscle. The parasympathetic ganglia of the rabbit and cat possess excitatory muscarinic receptors distinct from nicotinic and the vesical ganglia of the rat and dog may possess specific receptors for 5-HT. Adrenergic receptors, even though there were some species differences, are distributed throng hout whole bladder muscle and inhibitory β receptors are predominant in detrusor muscle, while excitatory α receptors are predominant in the trigone and bladder neck. The results of observation of the phenomena of atropine-resistance in vivo and in vitro state, strongly suggested that the atropine-resistant portion of the bladder might be mediated through non-cholinergic fibers.
[영문] A large portion of upper urinary tract infections are usually secondary to dysfunction of the bladder or urinary sphincter. In addition many lower urinary tract infections are directly related to decreased resistance of bladder tissue due to its abnormal bladder function. A knowledge of the mechanism of normal micturition and recognition of the aberrations is essential for accurate diagnosis and appropriate treatment. Though the pelvic nerve is the main motor innervation of the urinary bladder, contraction of the bladder by pelvic nerve stimulation or nicotinic ganglion stimulation is highly resistant to blockade by antimuscarinic agents. Concerning these atropine-resistant phenomena, there are two diametrically opposed points of view. One view insists that acetylcholine is the true transmitter agent and atropine-resistance is caused by the close adherence of motor nerve endings to the individual muscle cell or by a sufficiently high concentrations of acetylcholine released to overcome atropine black. The other is that acetylcholine is not the transmitter agent released at motor nerve endings. Rather, the true agent is unknown. The functional significance of the sympathetic bladder innervation is not clear. From previous and recent experiments it is known that an apparantly normal micturition also takes place in the absence of sympathetic nerves, although the volume is decreased. In sprite of remarkable advances in the fields of neuroanatomy and neuropharmacology, there still remain many controversial debates on the autonomic nerve control of the bladder, receptors, transmitters and the mutual interaction of autonomic nerves in micturition. The present study was designed to determine the contractile mechanism of the urinary bladder, e.g., the character of receptors to autonomic drugs and related agents in vivo and in vitro. Bladder muscle strips about 1.5cm in length were carefully isolated from the dome and trigone of the rat, cat, dog, rabbit and human. They were suspended in a muscle chamber containing 100ml of Tyrode solution maintained at a constant temperature of 38℃. The chamber was aerated with 95% oxygen and 5% carbondioxide bubbling through the bathing fluid by messrs of sintered glass plate at the bottom. The bladder strip was attached to the Grass force displacement transducer and the motility and tonus were recorded on a Grass model 7 polygraph. Being left in fresh Tyrode solution, the bladder strip attained a spontaneous motility and tonus. Then several drugs were added to the muscle chamber and the changes of motility of the strips were observed. In the cat and rabbit changes of intravesical pressure were recorded on a Grass model 7 polygraph by Statham P23 transducer after stimulation of the pelvic nerve and infusion of some drugs in situ. The results obtained were as follows. 1. Spontaneous rhythmic activity was observed in rat, cat, rabbit, dog and human bladder muscle strips. It was noted that there were some species differences in intensity of motility and generally the motility of detrusor strips was active, while the motility of trigone strips was weak and insignificant. 2. The inhibitory response of the detrusor strip to catecholamine was abolished by propranolol. 3. The excitatory response of the trigone strip to catecholamine was abolished and converted to relaxation by pretreatment with phenoxybenzamine and relaxation was abolished by propranolol. 4. In cat and rabbit, the increased contraction responses of detrusor strips were followed by the cholinergic and ganglionic stimulating agents and the effects were abolished by atropine, but the effect of TMA was only partially blocked by atropine. 5. In rabbit detrusor stored at 4℃ Tyrode solution for 2 weeks, there were no significant changes in motility or in histologic findings, but motility was difficult to preserve more than 2 days in detrusor strips of cat, dog and man. 6. Bladder contraction by pelvic nerve stimulation in situ wag partially blocked by atropine and was completely blocked by hexamethonium concomitantly. 7. Serotonin induced a remarkable contraction response in rat and dog detrusor strips. Prostaglandin E^^2 and F^^2α produced delayed and sluggish contractions, while imipramine produced delayed and long-lasting relaxation in rabbit detrusor strips. From the above results, it is suggested that cholinergic receptors are scattered throughout the entire bladder muscle. The parasympathetic ganglia of the rabbit and cat possess excitatory muscarinic receptors distinct from nicotinic and the vesical ganglia of the rat and dog may possess specific receptors for 5-HT. Adrenergic receptors, even though there were some species differences, are distributed throng hout whole bladder muscle and inhibitory β receptors are predominant in detrusor muscle, while excitatory α receptors are predominant in the trigone and bladder neck. The results of observation of the phenomena of atropine-resistance in vivo and in vitro state, strongly suggested that the atropine-resistant portion of the bladder might be mediated through non-cholinergic fibers.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/117267
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2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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