基于逼尿肌胶原蛋白及神经受体探讨缩泉丸作用机制
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摘要
中医认为,“肾主开阖”,具有主持和调节人体津液代谢的功能,尿的排泄,虽在膀胱,但要依赖肾阳的气化。若肾气充足,则能温煦膀胱,使之固摄有权、开阖有度,维持水液的正常代谢;若肾气不固,则致封藏失职,膀胱失约,出现多尿、遗尿、甚则小便失禁。机体的衰老状态被认为属于生理性肾虚的范畴,即老年人肾元亏虚,遇夜间阴盛阳衰,膀胱摄纳无权,易出现的夜尿、遗尿、尿急等症状。缩泉丸出自《校注妇人良方》,由乌药、益智仁、山药组成,具有温肾祛寒,缩尿止遗的功效,主治膀胱虚寒证,小便频数、遗尿不止等,现代临床被常用于夜尿、遗尿、尿频、尿急、尿失禁等老年下尿路功能症状等的治疗,其显著的临床疗效和治疗优势得到临床医师及病患的首肯。为了进一步阐明中医“温肾缩尿”理论,本课题组开展了一系列探索缩泉丸”缩尿”功效及关键作用靶点的研究,为中医经典理论的现代研究和缩泉丸的深层次研发奠定基础。
夜尿、尿频、遗尿、尿失禁等下尿路功能症状(LTUS)在老年人群中的发生率日趋增高,成为继心脑血管系统疾病后的又一大严重影响老年人身心健康和生活质量的重要因素。针对老年LTUS虽有包括行为矫正、神经调节、外科手术、针炙等疗法,但效果不甚理想,存在副作用大,复发率高,患者依从性较差等问题。近年来,关于老年LTUS的发病机制研究取得了较大进展,已证实引发老年LTUS的因素除神经、血管系统病变和膀胱流出道梗阻等尿道因素外,老龄本身对膀胱功能改变的影响也是重要因素之一。衰老的膀胱逼尿肌发生肌源性和神经源性的改变,导致逼尿肌舒缩功能障碍,出现储尿及排尿功能异常是引发老年LTUS的主要原因。
鉴于缩泉丸通过温补肾阳、温化肾气,达到“温肾缩尿”功效的治疗特色与现代医学所提及的通过调整膀胱逼尿肌功能状态失常治疗老年LTUS具有内在相关性,本研究以此为切入点,以中医传统古方缩泉丸为研究对象,并在成功复制衰老“多尿”动物模型并初步探讨其“多尿”机制的基础上,围绕缩泉丸干预调节尿液生成的相关因素和膀胱逼尿肌舒缩功能状态,对老年LTUS发病链上与尿液生成、排泄相关的各指标参数进行分析测定,并从对膀胱逼尿肌胶原蛋白、神经受体相关基因、蛋白表达调控的影响入手,从分子机制及“多尿”发生发展的重要环节探索缩泉丸“缩尿”作用机制和关键作用靶点,为进一步阐明中医“温肾缩尿”经典理论的现代医学内涵奠定基础。
衰老“多尿”动物模型的研究结果表明:
D-gal致亚急性衰老动物出现24h总尿量增加及水负荷后6h排尿潜伏期缩短、排尿次数增多,但总尿量没有明显改变的“多尿”症状。其多尿“机理”包括:(1)神经内分泌系统功能失调导致抗利尿激素(ADH)、醛固酮(ALD)合成与分泌减少,心钠素(ANP)分泌增加,尿液中水通道蛋白-2(AQP-2)浓度降低;肾脏病理形态学改变,包括肾单位数量减少,肾小管萎缩,近曲小管玻璃样变性等可能是模型动物24h总尿量增加的主要原因。(2)逼尿肌功能、组织酶学及病理形态学异常可能是模型动物排尿次数增多的主要原因。在组织酶学方面:逼尿肌丙二醛(MDA)含量增加,超氧化物歧化酶(SOD)、ATP酶(ATPase)、线粒体琥珀酸脱氢酶(SDH)活性降低;在功能改变方面:逼尿肌兴奋性增强,膀胱顺应性、弹性降低;对ATP敏感性增强的同时对ISO敏感性降低;在病理形态学方面:膀胱肌层肌纤维排列紊乱,血管壁纤维化,胶原纤维占肌层比例增加等。
缩泉丸“缩尿”功效的研究结果表明:
缩泉丸可减少亚急性衰老动物24h总尿量及水负荷后6h内排尿次数,延长排尿潜伏期。缩泉丸在减少动物尿液Na~+、Cl~-排出量的同时增加K~+排出量,说明药物具有保钠排钾的作用。缩泉丸可能通过恢复神经内分泌系统功能增加血中ALD、ADH,尿中AQP-2浓度及减少ANP的分泌及改善模型动物肾小球萎缩、硬化,肾小球基底膜增厚,入球血管硬化及肾小管萎缩等达到减少24h尿量的作用。缩泉丸可改善逼尿肌的衰老状态,使MDA含量降低,SOD活性增强,药物可能通过降低逼尿肌兴奋性及对ATP敏感性;增强Na~+-k~+-ATPase、Ca~(2+)-Mg~(2+)-ATPase,线粒体SDH活性,膀胱顺应性、弹性,对ISO敏感性及减轻逼尿肌肌层胶原纤维的增生,改善肌层肌纤维排列紊乱、增粗及肌纤维断裂等发挥延长水负荷后排尿潜伏期、减少排尿次数的作用。
缩泉丸对逼尿肌胶原蛋白及神经受体的影响研究结果表明:
缩泉丸可以从肌源性和神经源性两个角度调节逼尿肌胶原蛋白及神经受体的表达,恢复逼尿肌舒缩功能。从肌源性角度出发,缩泉丸可使衰老“多尿”大鼠膀胱逼尿肌collagenⅠ、collagenⅢmRNA及蛋白的表达显著降低,使动物由于衰老而异常沉积的胶原蛋白减少,增加了膀胱的顺应性及弹性,减轻衰老逼尿肌纤维化趋势;从神经源性角度,缩泉丸在降低介导逼尿肌收缩的P2X_2受体mRNA及蛋白的同时显著提高介导其舒张的β_3-AR mRNA及蛋白的表达,使两者保持动态平衡,恢复逼尿肌的正常舒缩功能。
亚急性衰老“多尿”动物模型的成功复制为本课题的研究提供了可靠的动物模型。缩泉丸通过影响尿液生成和排泄的多个环节发挥“缩尿”功效。药物可使老化逼尿肌舒缩功能恢复正常,这种作用与上调逼尿肌β_3-AR mRNA及蛋白的表达和下调collagenⅠ、collagenⅢ、P2X_2受体mRNA及蛋白的表达有关。缩泉丸”缩尿”功效的发挥与改善衰老“多尿”动物机体状态,调节神经-内分泌-免疫网络系统功能有关,充分体现中药复方多成分、多靶点、整体调节的作用特点及优势。
The low-tract urinary symptoms(LTUS) like nocturia、urinary frequency、enuresis、urinary incontinence,etc have a highly incidence rate in the elder people.Substituted heart and cerebrovascular system,it become the critical reason to effect physical and mental health and life quality of the aged people. According study,we find out the cause of the LTUS in the aged people not only the reason of urethra,like nerve system dysfunction,blood-vascular system affection and bladder outflow obstruction,but also the age itself.The function of capsular bladder is to urinate and store.This physiological function depend detrusor of bladder,a kind of main smooth muscle of bladder, to contract and relax.Because of physical and neurogenic changes,the senescent detrusor muscle occur functional impairment of contraction and relaxation.This is the main cause of elder LTUS.The formula of Suoquanwan(SQW) is recorded in a Chinese medicine book named Furenliangfang,which collected hundreds of formulas of Chinese medicine combinations.SQW consists of three herb medicines,Radix Linderae,Radix dioscoreae,and alpinia oxyphylla Miq. The function of SQW is to warm kidney,stop polyuria and hold excessive urination.This research duplicate the animal model of senile hyperdiuresis and observes the effect of arresting polyuria,collagen protein of musculus detrusor vesicae,neuroceptor related gene and regulatory protein related expression.This study from different Angles,like the molecular mechanism and the occurrence and development of polyuria,search for the mechanism of the formula SQW.
Objective:
On the basis of duplicating D-galactose mimetic aging animal model and exploring its mechanism of hyperdiuresis,observed the pharmacological action and molecular mechanism of SQW.
Methods:
Investigated the urination of D-galactose mimetic aging animal model, including total volume and ionic concentration of urine during 24h;We also observed the incubation period and frequency of urine within 6h after water load.The pharmacological mechanisms of SQW were investigated in following aspects:Investigated the hormones(including:ADH,ALD,ANP) and enzymes (including:ATPase,SDH) which influence the production and excretion of urine;the detrusor strips of each rat was suspended in a thermostatically controlled organ bath.And their spontaneous contraction frequency,reaction tension to stress and response intensity to electric stimuli were determined and statistically analyzed;The reactivity of urinary detrusor strips of each rat to different concentrations of ISO and ATP was measured respectively using an in vitro tissue bath technique;The pathological changes of kidney and bladder in rats were observed with HE,Masson,PAS dying method before and after SQW administration.The influence of SQW on expression of collagenⅠmRNA,collagenⅢmRNA,P2X_2 mRNA,β_3-AR mRNA in urinary detrusor strips of O-galactose mimetic aging animal model by RT-PCR;The influence of SQW on the in situ and protein expressions of collagenⅠ,collagenⅢ,P2X_2,β_3-AR in urinary detrusor strips of polyuria model by immunohistochemistry method.
Results:
1、The mechanism of polyuria for D-galactose mimetic aging model
The animal models have characteristics of polyuria.Total volume of urine during 24h increased.The incubation periods shorten and the frequency of urine increased within 6h after water load.There are about some reasons that caused these symptoms.(1) The synthesis and externalization of ADH and ALD decreased, at the same time,the level of ANP and AQP-2 increased.(2) The activities of SOD,Na~+-k~+-ATPase、Ca~(2+)-Mg~(2+)-ATPase and SDH in urinary detrusor strips are reduced.The frequency of spontaneous contraction was elevated significantly; The complaisance and elasticity of bladder were both attenuated.Compared with the young adult rats,significantly decreased relaxation response to high concentration of ISO and increased contractile response to ATP were found in aged model.Some histological changes were observed in aging model:the quantity of nephron was decreased,such as nephric tubule;glassy degeneration appeared in proximal convoluted tubule;the alinement of muscle fiber which in tunica muscularis vesicae urinariae was chaotic;fibrosis for vessel wall; the percentage of collagen fibers are increased.
2、The pharmacologic action of SQW
The results show that SQW reduce significantly the urine and the concentration of sodium,chlorine in urine,and elevate the excretion of urine potassium in aging rats.It also can improve the frequency of urine and extend incubation period of urine.SQW can increase the releasing of ALD,ADH and the concentration of AQP-2 in urine,meanwhile,it can reduce the content of ANP.SQW can delay the proceeding of aging in detrusor muscle.The activity of SOD,Na~+-k~+-ATPase,Ca~(2+)-Mg~(2+)-ATPase,SDH and complaisance and elasticity of bladder increased after SQW administration in aging rats.The frequency of spontaneous contraction was cut down significantly.The decreased relaxation response to ISO and increased contractile response to ATP were also changed after SQW administration.The pathological characteristics of kidney and bladder function were switched:nephric tubule analosis was improved;the hyperplasia of collagen fibers which in tunica muscularis vesicae urinariae and thickening,chaotic muscle fiber was decreased.
3、The molecular pharmacology mechanism of SQW
The results showed that both mRNA and protein expressions of collagenⅠ, collagenⅢ,P2X_2 were decreased and mRNA and protein expressions ofβ_3-AR was increased in D-galactose mimetic aging model with polyuria afer SQW administration.SQW can recover the normal physiologic function of detrusor of bladder by myogenic and neurogenic ways.
Conclusion:
Sucessful duplication of subacute aging animal model with polyuria provided a reliable and effective model for our study.SQW reduced significantly the urine through effecting the production and excretion of urine;it can recover the normal physiologic function of detrusor of bladder. This recovery might be through up-regulatingβ3-AR mRNA and its protein expression and down-regulating collagenⅠ,collagenⅢ,P2X2 mRNA and their protein expression.
夜尿、尿频、遗尿、尿失禁等下尿路功能症状(LTUS)在老年人群中的发生率日趋增高,成为继心脑血管系统疾病后的又一大严重影响老年人身心健康和生活质量的重要因素。针对老年LTUS虽有包括行为矫正、神经调节、外科手术、针炙等疗法,但效果不甚理想,存在副作用大,复发率高,患者依从性较差等问题。近年来,关于老年LTUS的发病机制研究取得了较大进展,已证实引发老年LTUS的因素除神经、血管系统病变和膀胱流出道梗阻等尿道因素外,老龄本身对膀胱功能改变的影响也是重要因素之一。衰老的膀胱逼尿肌发生肌源性和神经源性的改变,导致逼尿肌舒缩功能障碍,出现储尿及排尿功能异常是引发老年LTUS的主要原因。
鉴于缩泉丸通过温补肾阳、温化肾气,达到“温肾缩尿”功效的治疗特色与现代医学所提及的通过调整膀胱逼尿肌功能状态失常治疗老年LTUS具有内在相关性,本研究以此为切入点,以中医传统古方缩泉丸为研究对象,并在成功复制衰老“多尿”动物模型并初步探讨其“多尿”机制的基础上,围绕缩泉丸干预调节尿液生成的相关因素和膀胱逼尿肌舒缩功能状态,对老年LTUS发病链上与尿液生成、排泄相关的各指标参数进行分析测定,并从对膀胱逼尿肌胶原蛋白、神经受体相关基因、蛋白表达调控的影响入手,从分子机制及“多尿”发生发展的重要环节探索缩泉丸“缩尿”作用机制和关键作用靶点,为进一步阐明中医“温肾缩尿”经典理论的现代医学内涵奠定基础。
衰老“多尿”动物模型的研究结果表明:
D-gal致亚急性衰老动物出现24h总尿量增加及水负荷后6h排尿潜伏期缩短、排尿次数增多,但总尿量没有明显改变的“多尿”症状。其多尿“机理”包括:(1)神经内分泌系统功能失调导致抗利尿激素(ADH)、醛固酮(ALD)合成与分泌减少,心钠素(ANP)分泌增加,尿液中水通道蛋白-2(AQP-2)浓度降低;肾脏病理形态学改变,包括肾单位数量减少,肾小管萎缩,近曲小管玻璃样变性等可能是模型动物24h总尿量增加的主要原因。(2)逼尿肌功能、组织酶学及病理形态学异常可能是模型动物排尿次数增多的主要原因。在组织酶学方面:逼尿肌丙二醛(MDA)含量增加,超氧化物歧化酶(SOD)、ATP酶(ATPase)、线粒体琥珀酸脱氢酶(SDH)活性降低;在功能改变方面:逼尿肌兴奋性增强,膀胱顺应性、弹性降低;对ATP敏感性增强的同时对ISO敏感性降低;在病理形态学方面:膀胱肌层肌纤维排列紊乱,血管壁纤维化,胶原纤维占肌层比例增加等。
缩泉丸“缩尿”功效的研究结果表明:
缩泉丸可减少亚急性衰老动物24h总尿量及水负荷后6h内排尿次数,延长排尿潜伏期。缩泉丸在减少动物尿液Na~+、Cl~-排出量的同时增加K~+排出量,说明药物具有保钠排钾的作用。缩泉丸可能通过恢复神经内分泌系统功能增加血中ALD、ADH,尿中AQP-2浓度及减少ANP的分泌及改善模型动物肾小球萎缩、硬化,肾小球基底膜增厚,入球血管硬化及肾小管萎缩等达到减少24h尿量的作用。缩泉丸可改善逼尿肌的衰老状态,使MDA含量降低,SOD活性增强,药物可能通过降低逼尿肌兴奋性及对ATP敏感性;增强Na~+-k~+-ATPase、Ca~(2+)-Mg~(2+)-ATPase,线粒体SDH活性,膀胱顺应性、弹性,对ISO敏感性及减轻逼尿肌肌层胶原纤维的增生,改善肌层肌纤维排列紊乱、增粗及肌纤维断裂等发挥延长水负荷后排尿潜伏期、减少排尿次数的作用。
缩泉丸对逼尿肌胶原蛋白及神经受体的影响研究结果表明:
缩泉丸可以从肌源性和神经源性两个角度调节逼尿肌胶原蛋白及神经受体的表达,恢复逼尿肌舒缩功能。从肌源性角度出发,缩泉丸可使衰老“多尿”大鼠膀胱逼尿肌collagenⅠ、collagenⅢmRNA及蛋白的表达显著降低,使动物由于衰老而异常沉积的胶原蛋白减少,增加了膀胱的顺应性及弹性,减轻衰老逼尿肌纤维化趋势;从神经源性角度,缩泉丸在降低介导逼尿肌收缩的P2X_2受体mRNA及蛋白的同时显著提高介导其舒张的β_3-AR mRNA及蛋白的表达,使两者保持动态平衡,恢复逼尿肌的正常舒缩功能。
亚急性衰老“多尿”动物模型的成功复制为本课题的研究提供了可靠的动物模型。缩泉丸通过影响尿液生成和排泄的多个环节发挥“缩尿”功效。药物可使老化逼尿肌舒缩功能恢复正常,这种作用与上调逼尿肌β_3-AR mRNA及蛋白的表达和下调collagenⅠ、collagenⅢ、P2X_2受体mRNA及蛋白的表达有关。缩泉丸”缩尿”功效的发挥与改善衰老“多尿”动物机体状态,调节神经-内分泌-免疫网络系统功能有关,充分体现中药复方多成分、多靶点、整体调节的作用特点及优势。
The low-tract urinary symptoms(LTUS) like nocturia、urinary frequency、enuresis、urinary incontinence,etc have a highly incidence rate in the elder people.Substituted heart and cerebrovascular system,it become the critical reason to effect physical and mental health and life quality of the aged people. According study,we find out the cause of the LTUS in the aged people not only the reason of urethra,like nerve system dysfunction,blood-vascular system affection and bladder outflow obstruction,but also the age itself.The function of capsular bladder is to urinate and store.This physiological function depend detrusor of bladder,a kind of main smooth muscle of bladder, to contract and relax.Because of physical and neurogenic changes,the senescent detrusor muscle occur functional impairment of contraction and relaxation.This is the main cause of elder LTUS.The formula of Suoquanwan(SQW) is recorded in a Chinese medicine book named Furenliangfang,which collected hundreds of formulas of Chinese medicine combinations.SQW consists of three herb medicines,Radix Linderae,Radix dioscoreae,and alpinia oxyphylla Miq. The function of SQW is to warm kidney,stop polyuria and hold excessive urination.This research duplicate the animal model of senile hyperdiuresis and observes the effect of arresting polyuria,collagen protein of musculus detrusor vesicae,neuroceptor related gene and regulatory protein related expression.This study from different Angles,like the molecular mechanism and the occurrence and development of polyuria,search for the mechanism of the formula SQW.
Objective:
On the basis of duplicating D-galactose mimetic aging animal model and exploring its mechanism of hyperdiuresis,observed the pharmacological action and molecular mechanism of SQW.
Methods:
Investigated the urination of D-galactose mimetic aging animal model, including total volume and ionic concentration of urine during 24h;We also observed the incubation period and frequency of urine within 6h after water load.The pharmacological mechanisms of SQW were investigated in following aspects:Investigated the hormones(including:ADH,ALD,ANP) and enzymes (including:ATPase,SDH) which influence the production and excretion of urine;the detrusor strips of each rat was suspended in a thermostatically controlled organ bath.And their spontaneous contraction frequency,reaction tension to stress and response intensity to electric stimuli were determined and statistically analyzed;The reactivity of urinary detrusor strips of each rat to different concentrations of ISO and ATP was measured respectively using an in vitro tissue bath technique;The pathological changes of kidney and bladder in rats were observed with HE,Masson,PAS dying method before and after SQW administration.The influence of SQW on expression of collagenⅠmRNA,collagenⅢmRNA,P2X_2 mRNA,β_3-AR mRNA in urinary detrusor strips of O-galactose mimetic aging animal model by RT-PCR;The influence of SQW on the in situ and protein expressions of collagenⅠ,collagenⅢ,P2X_2,β_3-AR in urinary detrusor strips of polyuria model by immunohistochemistry method.
Results:
1、The mechanism of polyuria for D-galactose mimetic aging model
The animal models have characteristics of polyuria.Total volume of urine during 24h increased.The incubation periods shorten and the frequency of urine increased within 6h after water load.There are about some reasons that caused these symptoms.(1) The synthesis and externalization of ADH and ALD decreased, at the same time,the level of ANP and AQP-2 increased.(2) The activities of SOD,Na~+-k~+-ATPase、Ca~(2+)-Mg~(2+)-ATPase and SDH in urinary detrusor strips are reduced.The frequency of spontaneous contraction was elevated significantly; The complaisance and elasticity of bladder were both attenuated.Compared with the young adult rats,significantly decreased relaxation response to high concentration of ISO and increased contractile response to ATP were found in aged model.Some histological changes were observed in aging model:the quantity of nephron was decreased,such as nephric tubule;glassy degeneration appeared in proximal convoluted tubule;the alinement of muscle fiber which in tunica muscularis vesicae urinariae was chaotic;fibrosis for vessel wall; the percentage of collagen fibers are increased.
2、The pharmacologic action of SQW
The results show that SQW reduce significantly the urine and the concentration of sodium,chlorine in urine,and elevate the excretion of urine potassium in aging rats.It also can improve the frequency of urine and extend incubation period of urine.SQW can increase the releasing of ALD,ADH and the concentration of AQP-2 in urine,meanwhile,it can reduce the content of ANP.SQW can delay the proceeding of aging in detrusor muscle.The activity of SOD,Na~+-k~+-ATPase,Ca~(2+)-Mg~(2+)-ATPase,SDH and complaisance and elasticity of bladder increased after SQW administration in aging rats.The frequency of spontaneous contraction was cut down significantly.The decreased relaxation response to ISO and increased contractile response to ATP were also changed after SQW administration.The pathological characteristics of kidney and bladder function were switched:nephric tubule analosis was improved;the hyperplasia of collagen fibers which in tunica muscularis vesicae urinariae and thickening,chaotic muscle fiber was decreased.
3、The molecular pharmacology mechanism of SQW
The results showed that both mRNA and protein expressions of collagenⅠ, collagenⅢ,P2X_2 were decreased and mRNA and protein expressions ofβ_3-AR was increased in D-galactose mimetic aging model with polyuria afer SQW administration.SQW can recover the normal physiologic function of detrusor of bladder by myogenic and neurogenic ways.
Conclusion:
Sucessful duplication of subacute aging animal model with polyuria provided a reliable and effective model for our study.SQW reduced significantly the urine through effecting the production and excretion of urine;it can recover the normal physiologic function of detrusor of bladder. This recovery might be through up-regulatingβ3-AR mRNA and its protein expression and down-regulating collagenⅠ,collagenⅢ,P2X2 mRNA and their protein expression.
引文
[1]李仪奎主编.中药药理实验方法学[M].上海:上海科学技术出版社,2006年,第二版:992.
[2]Aston RA.Rat diuretic screening procedure[J].Toxicology and Applied Pharmacology,1959;1(3):277-282.
[3]王蕾,姚东云,马红梅.中药利尿药理实验动物筛选方法探讨[J].中国比较医学杂志,2006;16(11):694-695.
[4]Song X,Bao M,Li D,etal.Advanced glycation in D-galactose induced mouse aging model[J].Mech Aging Dev,1999;108(3):239.
[5]Zhang Q,Huang YG,Li XK,et al.GMlganglioside preven-ted the decline Of hippocampal neurogenesis associated with D-galactose[J].Neuropharmaeol and Neurotoxicol,2005;16(12):1297。
[6]朱亚珍,朱虹光.D-半乳糖致衰老动物模型的建立及其检测方法[J].复旦学报(医学版),2007;34(4):617-619.
[7]徐叔云,卞如濂,陈修主编.药理实验方法学[M].北京:人民卫生出版社,1985年,第一版:788.
[8]原文鹏,张硕峰,沈欣等.尿频康对大、小鼠排尿的抑制作用及药动学实验[J].中国实验方剂学杂志,2000,6(6):18.
[9]赵新鸿,宋波,熊恩庆,邱建宏.老龄大鼠膀胱生理特性改变的实验研究[J].华北国防医药,2005;17(6):387-390.
[10]邱功阔,宋波,金锡御等.膀胱出口梗阻对逼尿肌兴奋性、收缩性及顺应性影响的实验研究[J].中华泌尿外科杂志,2000;21(7):421-423.
[11]Waring JV,Wendt IR.Effects of streptozotocin-induced diabetes mellitus on intracellular calcium and contraction of longitudinal smooth muscle from rat urinary bladder[J].The Journal of Urology 2000;163(1):323-330.
[12]宋波.充盈性膀胱压力测定.金锡御,宋波主编.临床尿动力学[M].北京:人民卫生出版社,2002年,第一版:52-69.
[13]李云,杨素青,张军.急性致衰老动物模型的探讨[J],卫生研究,2002;31(4):290-291.
[14]徐敝本.D-半乳糖的亚急性毒性[C].第二届国际衰老研究会议,1985年,中国:哈尔滨.
[15]Sohal RS,Donato H.Eeffct of experimental prolongation of life Span on Lipofuscin content and lysomomal enzyme actively in the brain of housefly,Musca doestica[J].Georntol,19?9;34:489-496.
[16]刘汇波,邢善田.淫羊霍对抗D-半乳糖衰老模型的研究[J].中药药理与临床.1990;6(2):18-20.
[17]刘天培.人参与三七总皂苷对抗D-半乳糖所致小鼠虚损的研究[J].老年学杂志,1993;12(1):3-5.
[18]邢善田.D-半乳糖老化模型的研究及淫羊霍有效成分和枸杞多糖延缓衰老的作用.周金黄主编.中药免疫药理学[M].北京:人民军医出版社,1994:50-62.
[19]Benjumea D,Abdala S,Hernandez-Luis F,et al.Diuretic activity of Artemisia thuscula,an endemic Canary species[J].J Ethnopharmacol,2005;100(1-2):205-209.
[20]Taufiq-Ur-Rahman M,Shilpi JA,Ahmed M,et al.Preliminary pharmacological studies on Piper chaba stem bark[J].J Ethnopharmacol,2005:99(2):203-209.
[21]Johnson PB,Abdurahman EM,Tiam EA,et al.Euphorbia hirta leaf extracts increase urine output and electrolytes in rats [J].Ethnopharmacol,1999;65(1):63-69.
[22]徐智,吴国明,钱桂生.大鼠衰老模型的初步建立[J].第三军医大学学报,2003;25(4):312-315.
[23]Zhang Q,Huang YG,Li XK,et al.GMlganglioside prevented the decline of hippocampal neurogenesis associated with D-galactose[J].Neuropharmacol and Neurotoxicol,2005;16(12):1297.
[24]韩志涛,黄福南,房征宇等.D-半乳糖拟衰老模型大鼠的神经递质受体机制[J].中国临床康复,2006,;10(30):98-100.
[25]朱庆磊,薛桥,马路等.D-半乳糖催老大鼠氧化水平和抗氧化能力的变化[J].中国老年心血管杂志,2006;4(6):411-413.
[26]姚泰.生理学[M].北京:人民卫生出版社,2001年8月第一版.
[27]刘令梅.多尿[J].社区医学杂志,2006;4(10):16-17.
[28]Terris J,Ecelbarger CA,Nielsen S,et al.Long-term regulation of four renal aquaporins in rats[J].AmJ Physiol Renal Physiol,2000;278(4):F620-F627.
[29]Caldwell HK,Young WS "Oxytocin and Vasopressin:Genetics and Behavioral Implications",Handbook of Neurochemistry and Molecular Neurobiology[M],2006;3rd edition,Berlin:Springer,pages 573-607.
[30]Udo Hasler,David Mordasini,Matthieu Bianchi,et al.Dual Influence of Aldosterone on AQP2 Expression in Cultured Renal Collecting Duct Principal Cells.The Journal of Biological Chemistry,2003;(24):21639-21648.
[31]钟远,唐令诠.水通道蛋白的研究进展[J].《国外医学》泌尿系统分册,1999;19(4):178-180
[32]陈赘,孙则禹,朱伟东.醛固酮增多症的诊治[J].现代泌尿外科杂志,2007;12(3):207-211.
[33]张秀珍.内分泌代谢疾病与肾脏[M].上海:复旦大学出版社,2004,第一版
[34]Slight SH,Joseph J,Fanjam VK,et al.Extra-adrenal mineralocorticoid and cardiovascular tissue[J].J Am Mol Cell Cardiol,1999;31:1175-1184.
[35]Fakitsas P,Adam G,Daidie D,et al.Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation[J].Soc Nephrol,2007:18:1084-1092.
[36]高波,魏丛军.纤溶酶原激活物/I型纤溶酶原激活物抑制物的失衡在大鼠肾脏衰老过程中的意义[J].实用临床医药杂志,2004;8(4):17-21.
[37]都占陶,杨丽彩,危北海.补肾通络方对老龄大鼠肾功能的影响[J].中国中医基础医学杂志,2004;10(10):6-8.
[38]尹彤,徐斌,朱庆磊等.自然衰老与半乳糖催老小鼠重要脏器的形态学差异[J].中国临床康复,2004;8(36):8248-8251.
[39]鲁家才,库宝庆,莫扬.四项生化指标在肾功能损伤中的意义和临床评价[J].国际检验学杂志,2006;27(9):841-842.
[40]龚茜玲主编.人体解剖生理学[M].北京:人民卫生出版社,2004年,第四版:432.
[41]宋波,金锡御.尿动力学.李炎唐主编:泌尿外科高科技[M].北京:军事医学科学出版社,1998年,第一版:159.
[42]赵新鸿,宋波,熊恩庆,邱建宏.老龄大鼠膀胱生理特性改变的实验研究[J].华北国防医药,2005;17(6):387-390.
[43]廖利民,石炳毅,梁春泉.前列腺增生患者逼尿肌收缩力的定量判断与分级[J].中华外科杂志,1997:35:173-175.
[44]章振保,张时春,周芳坚.逼尿肌等容收缩实验[J].中华泌尿外科杂志.1998.19:309-311.
[45]成令忠.组织学与胚胎学[M].北京:人民卫生出版社,1978年,第一版:212-213.
[46]李新,宋波,李益人等.M受体及其亚型与逼尿肌功能的关系研究[M].第三军 医大学学报,2002;24(2):164-166.
[47]Grover A K.Calcium-handling studies using isolated smooth muscle membranes.In:Grover A K Daniel E E.Calcium and contractility,smooth muscle.Humana,Clifton,New Jersey,1985;245-269.
[48]Nordling J.The aging bladder-a significant but underestimated role in the development of lower urinary tract symptoms[J].Exp Gerontol.2002.37:991-999.
[49]Anderson KE.Clinical relevance of some findings in neuro-anatomy and neurophysiology of the lower urinary tract[J].Cli Sci.1986;70(suppl 14):21-32.
[50]Nordling J.The aging bladder-a significant but underestimated role in the development of lower urinary tract symptoms[J].Exp Gerontol,2002:37:991-999.
[51]Mastrigt RV.Age dependence of urinary bladder contractility[J].Neurourol Urodyn,1992:11:315.
[52]Melchior H.Disorders of bladder function in the elderly[J].Urologe A,1995:34:329-333.
[53]Gosling JA:Modification of bladder structure in response to outflow obstruction and ageing[J].Eur Urol,1997;32(Suppl1):9-14.
[54]Corns RA,Boolaky UV,Santer RM.Decreased calbindin-D28k immunoreactivity in aged rat sympathetic pelvic ganglionic neurons [J].Neurosci Lett,2000;292(2):91-94.
[55]Venegas JA.Viscoelostic properties of the contracting detrusor Ⅰ:theoretical basis[J].Am J physiol.1991.261:355-363.
[56]Yanmastrig TR,Tauechio EA.Series elastic properties of strips of smooth muscle for bladder[J].Med Biol Eng Comp,1992;20:585-594.
[57]Chun AL,Wallace LJ,Gerald MC,et al.Effects of age on urinary bladder function in the male rat[J].J Uroi,1989;141(1):170-173.
[58]Lluel P,Duquenne C,Martin D.Experimental bladder instability following bladder outlet obstruction in the female rat[J].Urol,1998;160:2253-2257.
[59]邱功阔,宋波,金锡御等.膀胱出口梗阻对逼尿肌兴奋性、收缩性及顺应性影响的实验研究[J].中华泌尿外科杂志,2000:21(7):421-423.
[60]吴阶平主编.泌尿外科[M].济南:山东科学技术出版社,1993年,第一版:801-831.
[61]吴阶平,马永江主编.实用泌尿外科学[M].北京:人民军医出版社,1991年,第一版:358-392.
[62]Jluel P,Palea S,Barras M,et al.Functional and morphological modifications of the uirnary bladder in aging female rats[J].Am J Physilo Regul Integr Comp Physiol,2000:278(4):964-972.
[63]Yamanishi T,Christopher R,Yoshida.K et al.The role of beta(3)-adreno receptors in mediating relaxation of porcine detrusor muscle[J].Br-J-Pharmacol,2002:135(1):129-34.
[64]Igawa Y,Takeda H,Yamazaki Y,et al.Function and molecule or biological evidence for possible β3-adrenoceptor in the human detrusor muscle[J].Br J Pharmacol,1999,126:819-825.
[65]刘建华,常波,史冀鹏.过度训练对大鼠心肌线粒体膜上功能性酶活性的影响[J].河北体育学院学报,2007;21(2):86-88.
[66]彭松林,顾玺,黄勇等.参附注射液对大鼠肝缺血再灌注SOD,GSH及ATP 酶的影响[J].广东医学,2007;28(1):24-25.
[67]赵云瞿,徐建兴.线粒体、活性氧和细胞凋亡[J].生物化学与生物物理进展,2001:28(2):169-173.
[68]Berridge M.Capacitative calcium entry[J].Biochemical Journal,1995:3(12):1.
[69]Levy J,Gavin J R,Sowers J R.Diabetes Mellitus:A disease of abnormal cellular calcium metabolism?[J]American Journal of Medical,1994:96(3):260.
[70]韩贻仁主编.分子细胞生物学[M].北京:科学出版社,2001.
[71]Comellas A P,Dada L A,Lecuona E,et al.Hypoxia—mediated degradation of Na,K—ATPase viamitochondrial reactive oxygenspecies and the ubiquitin-conjugating system[J].CircRes,2006;98(10):1314-1316.
[72]金惠铭主编.病理生理学[M].北京:人民卫生出版社,1999.
[73]王镜岩,朱圣庚,徐长法.生物化学[M].北京:高等教育出版社,2002,第一版.
[74]辛明秀,周培瑾.冷活性琥珀酸脱氢酶的特性[J].北京师范大学学报,2004;40(1):108-113
[75]Beckman KB,Ames BN.The free radical theory of aging mature[J].Physiology Review.1999:78(2):547-581.
[76]赵新鸿.膀胱逼尿肌结构功能变化的老龄相关性影响研究进展[J].国外医学泌尿系统分册,2003;23(3):277-280.
[77]吕圭源主编.药理学[M].北京:中国中医药出版社,2003年2月,第一版.
[78]郭红,张文博,李翠香.充血性心力衰竭治疗的新靶点-醛固酮受体[J].滨州医学院学报,2004:27(5):356-357
[79]张秀珍.内分泌代谢疾病与肾脏[M].上海:复旦大学出版社,2004年,第一版
[80]Slight SH,Joseph J,Fanjam VK,et al.Extra-adrenal mineral ocorticoidsand cardiovascular tissue[J].Mol Cell Cardiol,1999;31(3):1175-1184.
[81]Seldin,D.W,Giedich G.The Kidney,Physiology and Pathophysiology.Lippincott,Williams and Wilkins,Philadelphia,PA 2000;3rd Ed,pp.1009-1471.
[82]丁原全,于天晓,赵楠.肾虚与衰老关系探要[J].实用中医内科杂志,2008,22(2):33-34.
[83]MeitesJ.Neuroendoerinology of aging[M].NewYork and London:Pleunm press,2003,23(1):349.
[84]沈自尹,王文健,张玲娟.从肾阳虚和老年人的不同反馈模式讨论阴阳学说[J].中西医结合杂志,1996;6(10):628.
[85]Ishunina TA,Swaah DF.Vasopressin and oxytocin neurons of thehuman supraoptic and paraventricular nucleus:size changes in relation to age and sex[J].J Clin Endocrinol Metab 1999;84(12):4637-4644.
[86]Dent GW,Okimoto DK,Smith MA,et al.Tress-induced alterations in corticotropin—releasing hormone and vasopressin gene expression in the paraventricular nucleus during ontogeny[J].Neuroendocrinology,2000;71(6):333-342.
[87]Knepper MA.Am J Physiol,1997;72:F3-F12.
[88]Lee MD,King LS,Agre P[M].Medicine,1997;76:141-156.
[89]Ishibashi K,Sasaki S,Fushimi K,et al.Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells[J].Proc Natl Acad Sci U S A,1994;91(14):6269-6273.
[90]King LS,Yasui M,Agre P.Molecul Med Today,2000;6:60-65.
[91]Frokiaer J,Marple D,Knepper MA,et al.Am J MedSci,1998;316:291-299.
[92]Marples D,Christensen S,Christensen EI et al.Lithium-induced down-regulation of aquaporin2 water channel expression in rat kidney medulla[J].Clin Invest,1995;95:1838.
[93]Sands J M,Naruse M,Jacobs JD et al.Changes in aquaporin2 protein contribute to the urine concentrating defect in rats fed a low protein diet[J].ClinInvest,1996;97:2807.
[94]Marples D,Frokiaer J,Dorup J et al.Hypokalemia- induced down regulation of aquaporin2 water channel expression in rat kidney medulla and cortex[J].ClinInvest,1996;97:1960.
[95]Deen P M,Verdijk M A,Knoers N V et al.Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine[J].Science,1994;264:92.
[96]邓英姿,许顶立,张远慧.尿液中水孔蛋白22的检测及其与肾组织中表达的相关性[J].肾脏病与透析肾移植杂志,1999;8(4):312-314.
[97]Watters JJ,Poulin P,Doras,DM,et al.Sterio hormone regulation of vasopresginergic neurotransmission in the central nervous system[J].Prog Brain Res,1998;119:247-261.
[98]Gabrielsen A,Warberg J.Christensen NJ,et al.Arterial pulsepressure and vasopressin release graded water immersion in humans[J].Am J Physiol Regul Integr Comp Physiol,2000;278(6):1583-1588.
[99]Gulati K,Lall SB.Angiotensin Ⅱ-receptor subtypes characterization and pathophysiological implications[J].Exp Biol,1996;34(2):91-97.
[100]Van de Heijining BJ,Maigret C,Koekkoek-van den herik I,et al.Dynorphin-A and vasopressin release in the rat:a structure-activity study[J].Neuropeptides,1994;(26):371-378.
[101]DeM GW,OKimoto DK.Smith MA,et al.Stress-induced alterations in cortieotropin-releasing honnone and vasopressin gene expression in the paraventricular nucleus during ontogeny[5].Neuroendocrinology,2000;71(6):333-342.
[102]宋波.有关逼尿肌功能的理解和研究[J].临床泌尿外科杂志,2004;19(11):641-642.
[103]吴博威.第二章细胞的基本功能.姚泰.主编.生理学(七年制临床医学等专业用)[M]北京:人民卫生出版社,2001年.
[104]宋波.逼尿肌兴奋性及逼尿肌不稳定[J].第三军医大学学报,2003,25(22)1969-1971
[105]Abrams P.Urodynamics[M].London:Spriger Verlag London Limited,1997;233-246.
[106]Groat WC.Anatomy of the central neural pathways controlling the lower urinary tract[J].Eur Urol,1998,34(Suppl 1):2-5.
[107]何地英,瞿颂义.药物对膀胱逼尿肌的影响[J].兰州医学院学报,1996;22(1):27-28.
[108]Bayliss M,Wu C,Newgreen D,et al.A quantitative study of atropine resistant contractile responses in human detrusor smooth muscle,from stable,unstable and obstructed bladders[J].Urol,1999;162(5):1833-1839.
[109]Zhakh BS,Burnstock G,Kennedy C,et al.International union of pharmacology.ⅩⅩⅣ.Current status of the nomenclature and properties of P2X receptors and their subunits[J].Pharmacol Rev,2001,53(1):107-18.
[110]North RA.Molecular physiology of P2X receptors[J].Physiol Rev,2002;82(4):1013-67.
[111]Longhurst P A,Eika B,Leggett R E,et al.Comparison of urinary bladder function in 6 and 24 month male and female rats[J]Urol,1992;148(5):1615-1620.
[112]Gosling J A.Modification of bladder structure in response to outflow obstruction and ageing[J].Eur Urol,1997;32(Suppl 1):9-14.
[113]Nishimoto T,Latifpour J,Wheeler M A,et al.Age-dependent alterationsin beta-adrenergic responsiveness of rat detrusor smooth muscle[J].Urol,1995;153(5):1701-1705.
[114]Saito M,Kondo A,Gotoh M,et al.Age-related changes in the response of the rat urinary bladder to neurotransmitters[J].Neurourol Urodyn,1993;12(2):191-200.
[115]Kageyama S,Fujita K,Suzuki K,et al.Effect of age on the responses of rat bladder detrusor strips to adenosine triphosphate[J].BJU Int,2000:85(7):899-904.
[116]龚国清.小鼠衰老模型研究[J].中国药科大报,1991,22(2):101.
[117]樊新荣,黄贵华,朱文锋.太阴病脾虚寒湿证大鼠模型的建立与机理探讨[J].中华中医药学刊,2008;26(1):58-60.
[118]Somlyo A P,Somlyo A V.Signal transduction and regulation in smooth muscle[J].Nature,1994:372(1):231.
[119]Berridge M.Capacitative calcium entry[J].Biochemical Journal,1995;3(12):1.
[120]Fuller W,Parmar V,Eaton P,et al.Cardiac isehemia causes inhibition of the Na/K ATPase by a labile cytosolic compound whose Production is linked to oxidant stress[J].Cardiovasc Res,2003;57(4):i044-i049.
[121]卢圣栋主编.现代分子生物学实验技术[M].北京:高等教育出版社,1993年。
[122]Landau E H,Jayanthi V R,Oatadaill BM,et al.Loss of elasticity in dysfunctional bladders urodynamic and histochmaical correlation[J].Urol,1994;152(2):702-705.
[123]Ewalt D H,Howard P S,Blyth B,et al.Is lamina propria matrix responsible for normal bladder compliance?[J].Urol,1992;148(2):544-549.
[124]Tekgul S,Yashino K Bagli D et al.Collagen types Ⅰ and Ⅲlocalization by in hybridization and immunohistochemistry in the partially obstruction young rabbit bladder[J].Urol,1996:156(2):582-586.
[125]Ewalt D H,Constantinescn S C,Bellno G,et al.Increased collagen type Ⅲ in the neurogenic non-compliant bladdre[J].Urol,1992;147(2):438-452.
[126]Bylund D B,Eikenberg D C,Hieble J P,et al.International Union of Pharmacology nomenclature of adrenoceptors[J].Pharmacol-Rev,1994;46(2):121-136.
[127]Beech D J.Actions of neurotransmitters and other messengers on Ca2+channels and K+ channels in smooth muscle cells[J].Pharmacol Ther,1997;73(2):91-119.
[128]杨听,宋波,方强等.P2X受体亚型在大鼠逼尿肌不稳定中的作用研究.第三军医大学学报[J].2004;26(8):710-713.
[129]马琳,王伟,高红.P2X受体亚型在新生儿膀肤中的表达及其意义[J].中华小儿外科杂志,2007;3(28):164-165.
[130]董晓华,张丹参,武海霞.衰老动物模型的研究进展及评价[J].河北北方学院学报,2004;21(6):41-43.
[131]陈勤.抗衰老研究试验方法[M].北京:中国医药科技出版社,1996年,第一版.
[132]夏寿首.放射生物学[M].北京:军事医学出版社,1998年,第一版:22-44.
[133]陈友琴,胡新抿,刘鸿莲,幸浩洋.YN-PTOL对衰老模型自由基损伤的保 护作用[J].中国医学物理学杂志,2000;7(1):57-58.
[134]崔英俊,李庆章.滑菇多糖对衰老模型鼠不同时期免疫功能的影响[J].东北农业大学学报,2004;35(2):129-134.
[135]Minako K,Noboru M,Kohji K et al.Abnormal accumulation of luteal bodies in ovaries of the senescence accelerated mouse(SAM)[J].The Journal of Reproduction and Development,2001;47(3):153-164.
[136]Suganuma H,Kaburagi S,Inakuma T et al.Amelioratory effect of dietary ingestion of lycopene and tomato rich inlympene on learning impairment in senescence-accelerated mice(SAMP8)[J].Food science and technology research,2002;8(2),183-187.
[137]韩景献.快速老化模型小白鼠(SAM)的老化诸特征及脑老化研究.陈可冀主编,跨世纪脑科学-老年痴呆发病机理与诊治[M].北京:北京医科大学中国协和医科大学联合出版社,1998年12月.
[138]赵湘媛,张石宁,陈明.β-淀粉样蛋白致大鼠衰老模型及单胺类递质改变[J].脑与神经疾病杂志,2001;9(6):333-335.
[139]魏小龙,张永祥.老年性痴呆动物模型研究进展[J].中国药理学通报,2000;16(4):372-37.
[140]许东晖,黄世亮,梅雪婷等.海星甾醇对AlCl3致急性衰老小鼠记忆障碍的保护作用及其机制[J].中国药理学通报,2000,16(4):432-435.
[141]崔旭,李文彬,张炳烈等.D-半乳糖拟脑老化模型的脂质过氧化机理[J].中国老年学杂志,1998;18(1):38-40.
[142]Song X,Bao M,Ii D et al.Advanced glycation in D-galactose induced mouse aging model[J].Mechanisms of Ageing and Development,1999;108(3):239-251.
[143]马虹,徐镰,田苏平等.不同水温游泳对小鼠行为、记忆和脂质过氧化影响差异的研究[J].中国应用生理学杂志,1999;15(3):222-225.
[144]刘晓秋,李卫东,唐惠琼,连至诚.D-半乳糖衰老大鼠自由基代谢状况分析[J].中国老年学杂志,2001:21(6):456-458.
[145]姜招峰,周翔,杨翰仪.海马及皮层的氧自由基损伤与大鼠学习能力和记忆能力的关系[J].中国行为医学杂志,2001;10(4):286-288.
[146]龚锅清.小鼠衰老模型研究[J].中国药科大学学报.1991,22(2)101-103.
[147]李文彬,韦丰,范明等.D-半乳糖在小鼠上诱导的拟脑老化效应.[J].中国药理学与毒理学杂志,1995;9(2):93-95.
[148]钱小明.吴振国.施志明.等.衰老小鼠组织牛磺酸含量与脂质过氧化损伤 的关系[J].基础医学与临床.1995;15(7):390.
[149]王少康,孙桂菊,张建新等.亚急性衰老动物模型的建立及评价[J].东南大学学报(医学版),2002;21(3):217-220.
[150]原文鹏,张硕峰,沈欣等.尿频康对大、小鼠排尿的抑制作用及药动学实验[J].中国实验方剂学杂志,2000;6(6):18-20.
[151]沈自尹,王文建.中医虚证辩证参考标准[J].中西医结合杂志,1986;6:59.
[152]金锡御,宋波.临床尿动力学[M].北京:人民卫生出版社,2002年,第一版.
[153]何地英,瞿颂义.膀肌逼尿肌的组织及生理学概述[J].西北民族大学学报(自然科学版),2005;26(60):82-85.
[154]李新,宋波,李益人等.M受体及其亚型与逼尿肌功能的关系研究[J].第三军医大学学报,2002;24(2):164-166.
[155]刘南,宋波,金锡御.大鼠低顺应性膀胱中Ⅰ型和Ⅲ型胶原蛋白的基因表达[J].第三军医大学学报,2003;25(5):505-507.
[156]Jluel P,Palea S,Barras M,etal.Functional and morphological modifications of the uirnary bladder in aging female rats[J].Am J Physilo Regul Integr Comp Physiol,2000;278(4):984-972.
[157]Schwiebert E M,Zsembery A.Extracellular ATP as a sigma lingmole cule for epithelial cells[J].Biochim Biophys Acta,2003;1615(1-2):7-32.
[158]Boehm S.Signaling via nucleotide receptors in the sympathetic nervous system[J].Drug News Perspect,2003;16(3):141-148.
[159]North RA,Surprenant A.Pharmacology of cloned P2X receptors[J].Annuual Review of Pharmacology Toxicology,2000;40:563-580.
[160]Khakh B S,Burnstock G,Kennedy C,et al.International union of pharmacology.ⅩⅩⅣ.Current status of the nomenclature and properties of P2X receptors and their subunits[J].Pharmacol Rev,2001;53(1):107-118.
[161]李为兵,方强,杨听等.ATP对正常及DI大鼠离体逼尿肌肌条自发性收缩的影响[J].第三军医大学报,2005;27(14):1459-1462.
[162]李为兵.ATP及其受体P2X参与膀胱感觉的研究进展[J].国际泌尿系统杂志,2006;26(6):782-785.
[163]O'Reilly BA,Kosaka AH,Knight GF.P2X receptors and their role in female idiopathic detrusor instability[J].Urol,2002;167(1):157-164.
[164]Osamn Y.β3-adrenoceptors in human detrusor muscle[J].Urology, 2002;59(suppl 5A):25.
[165]Igawa Y,Takeda H,Yamazaki Yet al.Function and molecule or biological evidence for possible β3-adrenoceptor in the human detrusor muscle[J].Br J Pharmacol,1999,126:819.
[166]曹文峰,宋波,陈昭领等.β3-AR介导逼尿肌舒张信号转导机制的实验研究[J].解放军医学杂志,2004;29(6):516-518.
[167]Seguchi H,Nishimura J,Yinbi Zet al.Expression of β3-adrenoceptors in rat detrusor smooth muscle[J].J Urol,1998:159:2197.
[168]孙则禹.肾上腺素能受体与下尿路症状[J].江苏医药,2005;31(3):214-215.
[169]Krief S,Lonnqvist F,Raimbault S,et al.Tissue distribution of beta 3-adrenergic receptor mRNA in man[J].J CIin Invest,1993;91(1):344-349.
[170]Penelope A.Longhurst M.Pharmacological characterization of β-adreno ceptors mediating relaxation of the rat urinary bladder in vitro[J].Br J Pharmacol,1999;127:1744-1750.
[171]曹文峰,宋波,金锡御等.肾上腺素β受体在大鼠逼尿肌中的表达及功能[J].解放军医学杂志,2003;28(2):137-139.
[172]Nishimoto T,Latifpour J,Wheeler A M,et al.Age dependent alteration in β-adrenergic responsiveness of rat detrusor smooth muscle[J].J Urol,1995;153:1701-1705.
[2]Aston RA.Rat diuretic screening procedure[J].Toxicology and Applied Pharmacology,1959;1(3):277-282.
[3]王蕾,姚东云,马红梅.中药利尿药理实验动物筛选方法探讨[J].中国比较医学杂志,2006;16(11):694-695.
[4]Song X,Bao M,Li D,etal.Advanced glycation in D-galactose induced mouse aging model[J].Mech Aging Dev,1999;108(3):239.
[5]Zhang Q,Huang YG,Li XK,et al.GMlganglioside preven-ted the decline Of hippocampal neurogenesis associated with D-galactose[J].Neuropharmaeol and Neurotoxicol,2005;16(12):1297。
[6]朱亚珍,朱虹光.D-半乳糖致衰老动物模型的建立及其检测方法[J].复旦学报(医学版),2007;34(4):617-619.
[7]徐叔云,卞如濂,陈修主编.药理实验方法学[M].北京:人民卫生出版社,1985年,第一版:788.
[8]原文鹏,张硕峰,沈欣等.尿频康对大、小鼠排尿的抑制作用及药动学实验[J].中国实验方剂学杂志,2000,6(6):18.
[9]赵新鸿,宋波,熊恩庆,邱建宏.老龄大鼠膀胱生理特性改变的实验研究[J].华北国防医药,2005;17(6):387-390.
[10]邱功阔,宋波,金锡御等.膀胱出口梗阻对逼尿肌兴奋性、收缩性及顺应性影响的实验研究[J].中华泌尿外科杂志,2000;21(7):421-423.
[11]Waring JV,Wendt IR.Effects of streptozotocin-induced diabetes mellitus on intracellular calcium and contraction of longitudinal smooth muscle from rat urinary bladder[J].The Journal of Urology 2000;163(1):323-330.
[12]宋波.充盈性膀胱压力测定.金锡御,宋波主编.临床尿动力学[M].北京:人民卫生出版社,2002年,第一版:52-69.
[13]李云,杨素青,张军.急性致衰老动物模型的探讨[J],卫生研究,2002;31(4):290-291.
[14]徐敝本.D-半乳糖的亚急性毒性[C].第二届国际衰老研究会议,1985年,中国:哈尔滨.
[15]Sohal RS,Donato H.Eeffct of experimental prolongation of life Span on Lipofuscin content and lysomomal enzyme actively in the brain of housefly,Musca doestica[J].Georntol,19?9;34:489-496.
[16]刘汇波,邢善田.淫羊霍对抗D-半乳糖衰老模型的研究[J].中药药理与临床.1990;6(2):18-20.
[17]刘天培.人参与三七总皂苷对抗D-半乳糖所致小鼠虚损的研究[J].老年学杂志,1993;12(1):3-5.
[18]邢善田.D-半乳糖老化模型的研究及淫羊霍有效成分和枸杞多糖延缓衰老的作用.周金黄主编.中药免疫药理学[M].北京:人民军医出版社,1994:50-62.
[19]Benjumea D,Abdala S,Hernandez-Luis F,et al.Diuretic activity of Artemisia thuscula,an endemic Canary species[J].J Ethnopharmacol,2005;100(1-2):205-209.
[20]Taufiq-Ur-Rahman M,Shilpi JA,Ahmed M,et al.Preliminary pharmacological studies on Piper chaba stem bark[J].J Ethnopharmacol,2005:99(2):203-209.
[21]Johnson PB,Abdurahman EM,Tiam EA,et al.Euphorbia hirta leaf extracts increase urine output and electrolytes in rats [J].Ethnopharmacol,1999;65(1):63-69.
[22]徐智,吴国明,钱桂生.大鼠衰老模型的初步建立[J].第三军医大学学报,2003;25(4):312-315.
[23]Zhang Q,Huang YG,Li XK,et al.GMlganglioside prevented the decline of hippocampal neurogenesis associated with D-galactose[J].Neuropharmacol and Neurotoxicol,2005;16(12):1297.
[24]韩志涛,黄福南,房征宇等.D-半乳糖拟衰老模型大鼠的神经递质受体机制[J].中国临床康复,2006,;10(30):98-100.
[25]朱庆磊,薛桥,马路等.D-半乳糖催老大鼠氧化水平和抗氧化能力的变化[J].中国老年心血管杂志,2006;4(6):411-413.
[26]姚泰.生理学[M].北京:人民卫生出版社,2001年8月第一版.
[27]刘令梅.多尿[J].社区医学杂志,2006;4(10):16-17.
[28]Terris J,Ecelbarger CA,Nielsen S,et al.Long-term regulation of four renal aquaporins in rats[J].AmJ Physiol Renal Physiol,2000;278(4):F620-F627.
[29]Caldwell HK,Young WS "Oxytocin and Vasopressin:Genetics and Behavioral Implications",Handbook of Neurochemistry and Molecular Neurobiology[M],2006;3rd edition,Berlin:Springer,pages 573-607.
[30]Udo Hasler,David Mordasini,Matthieu Bianchi,et al.Dual Influence of Aldosterone on AQP2 Expression in Cultured Renal Collecting Duct Principal Cells.The Journal of Biological Chemistry,2003;(24):21639-21648.
[31]钟远,唐令诠.水通道蛋白的研究进展[J].《国外医学》泌尿系统分册,1999;19(4):178-180
[32]陈赘,孙则禹,朱伟东.醛固酮增多症的诊治[J].现代泌尿外科杂志,2007;12(3):207-211.
[33]张秀珍.内分泌代谢疾病与肾脏[M].上海:复旦大学出版社,2004,第一版
[34]Slight SH,Joseph J,Fanjam VK,et al.Extra-adrenal mineralocorticoid and cardiovascular tissue[J].J Am Mol Cell Cardiol,1999;31:1175-1184.
[35]Fakitsas P,Adam G,Daidie D,et al.Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation[J].Soc Nephrol,2007:18:1084-1092.
[36]高波,魏丛军.纤溶酶原激活物/I型纤溶酶原激活物抑制物的失衡在大鼠肾脏衰老过程中的意义[J].实用临床医药杂志,2004;8(4):17-21.
[37]都占陶,杨丽彩,危北海.补肾通络方对老龄大鼠肾功能的影响[J].中国中医基础医学杂志,2004;10(10):6-8.
[38]尹彤,徐斌,朱庆磊等.自然衰老与半乳糖催老小鼠重要脏器的形态学差异[J].中国临床康复,2004;8(36):8248-8251.
[39]鲁家才,库宝庆,莫扬.四项生化指标在肾功能损伤中的意义和临床评价[J].国际检验学杂志,2006;27(9):841-842.
[40]龚茜玲主编.人体解剖生理学[M].北京:人民卫生出版社,2004年,第四版:432.
[41]宋波,金锡御.尿动力学.李炎唐主编:泌尿外科高科技[M].北京:军事医学科学出版社,1998年,第一版:159.
[42]赵新鸿,宋波,熊恩庆,邱建宏.老龄大鼠膀胱生理特性改变的实验研究[J].华北国防医药,2005;17(6):387-390.
[43]廖利民,石炳毅,梁春泉.前列腺增生患者逼尿肌收缩力的定量判断与分级[J].中华外科杂志,1997:35:173-175.
[44]章振保,张时春,周芳坚.逼尿肌等容收缩实验[J].中华泌尿外科杂志.1998.19:309-311.
[45]成令忠.组织学与胚胎学[M].北京:人民卫生出版社,1978年,第一版:212-213.
[46]李新,宋波,李益人等.M受体及其亚型与逼尿肌功能的关系研究[M].第三军 医大学学报,2002;24(2):164-166.
[47]Grover A K.Calcium-handling studies using isolated smooth muscle membranes.In:Grover A K Daniel E E.Calcium and contractility,smooth muscle.Humana,Clifton,New Jersey,1985;245-269.
[48]Nordling J.The aging bladder-a significant but underestimated role in the development of lower urinary tract symptoms[J].Exp Gerontol.2002.37:991-999.
[49]Anderson KE.Clinical relevance of some findings in neuro-anatomy and neurophysiology of the lower urinary tract[J].Cli Sci.1986;70(suppl 14):21-32.
[50]Nordling J.The aging bladder-a significant but underestimated role in the development of lower urinary tract symptoms[J].Exp Gerontol,2002:37:991-999.
[51]Mastrigt RV.Age dependence of urinary bladder contractility[J].Neurourol Urodyn,1992:11:315.
[52]Melchior H.Disorders of bladder function in the elderly[J].Urologe A,1995:34:329-333.
[53]Gosling JA:Modification of bladder structure in response to outflow obstruction and ageing[J].Eur Urol,1997;32(Suppl1):9-14.
[54]Corns RA,Boolaky UV,Santer RM.Decreased calbindin-D28k immunoreactivity in aged rat sympathetic pelvic ganglionic neurons [J].Neurosci Lett,2000;292(2):91-94.
[55]Venegas JA.Viscoelostic properties of the contracting detrusor Ⅰ:theoretical basis[J].Am J physiol.1991.261:355-363.
[56]Yanmastrig TR,Tauechio EA.Series elastic properties of strips of smooth muscle for bladder[J].Med Biol Eng Comp,1992;20:585-594.
[57]Chun AL,Wallace LJ,Gerald MC,et al.Effects of age on urinary bladder function in the male rat[J].J Uroi,1989;141(1):170-173.
[58]Lluel P,Duquenne C,Martin D.Experimental bladder instability following bladder outlet obstruction in the female rat[J].Urol,1998;160:2253-2257.
[59]邱功阔,宋波,金锡御等.膀胱出口梗阻对逼尿肌兴奋性、收缩性及顺应性影响的实验研究[J].中华泌尿外科杂志,2000:21(7):421-423.
[60]吴阶平主编.泌尿外科[M].济南:山东科学技术出版社,1993年,第一版:801-831.
[61]吴阶平,马永江主编.实用泌尿外科学[M].北京:人民军医出版社,1991年,第一版:358-392.
[62]Jluel P,Palea S,Barras M,et al.Functional and morphological modifications of the uirnary bladder in aging female rats[J].Am J Physilo Regul Integr Comp Physiol,2000:278(4):964-972.
[63]Yamanishi T,Christopher R,Yoshida.K et al.The role of beta(3)-adreno receptors in mediating relaxation of porcine detrusor muscle[J].Br-J-Pharmacol,2002:135(1):129-34.
[64]Igawa Y,Takeda H,Yamazaki Y,et al.Function and molecule or biological evidence for possible β3-adrenoceptor in the human detrusor muscle[J].Br J Pharmacol,1999,126:819-825.
[65]刘建华,常波,史冀鹏.过度训练对大鼠心肌线粒体膜上功能性酶活性的影响[J].河北体育学院学报,2007;21(2):86-88.
[66]彭松林,顾玺,黄勇等.参附注射液对大鼠肝缺血再灌注SOD,GSH及ATP 酶的影响[J].广东医学,2007;28(1):24-25.
[67]赵云瞿,徐建兴.线粒体、活性氧和细胞凋亡[J].生物化学与生物物理进展,2001:28(2):169-173.
[68]Berridge M.Capacitative calcium entry[J].Biochemical Journal,1995:3(12):1.
[69]Levy J,Gavin J R,Sowers J R.Diabetes Mellitus:A disease of abnormal cellular calcium metabolism?[J]American Journal of Medical,1994:96(3):260.
[70]韩贻仁主编.分子细胞生物学[M].北京:科学出版社,2001.
[71]Comellas A P,Dada L A,Lecuona E,et al.Hypoxia—mediated degradation of Na,K—ATPase viamitochondrial reactive oxygenspecies and the ubiquitin-conjugating system[J].CircRes,2006;98(10):1314-1316.
[72]金惠铭主编.病理生理学[M].北京:人民卫生出版社,1999.
[73]王镜岩,朱圣庚,徐长法.生物化学[M].北京:高等教育出版社,2002,第一版.
[74]辛明秀,周培瑾.冷活性琥珀酸脱氢酶的特性[J].北京师范大学学报,2004;40(1):108-113
[75]Beckman KB,Ames BN.The free radical theory of aging mature[J].Physiology Review.1999:78(2):547-581.
[76]赵新鸿.膀胱逼尿肌结构功能变化的老龄相关性影响研究进展[J].国外医学泌尿系统分册,2003;23(3):277-280.
[77]吕圭源主编.药理学[M].北京:中国中医药出版社,2003年2月,第一版.
[78]郭红,张文博,李翠香.充血性心力衰竭治疗的新靶点-醛固酮受体[J].滨州医学院学报,2004:27(5):356-357
[79]张秀珍.内分泌代谢疾病与肾脏[M].上海:复旦大学出版社,2004年,第一版
[80]Slight SH,Joseph J,Fanjam VK,et al.Extra-adrenal mineral ocorticoidsand cardiovascular tissue[J].Mol Cell Cardiol,1999;31(3):1175-1184.
[81]Seldin,D.W,Giedich G.The Kidney,Physiology and Pathophysiology.Lippincott,Williams and Wilkins,Philadelphia,PA 2000;3rd Ed,pp.1009-1471.
[82]丁原全,于天晓,赵楠.肾虚与衰老关系探要[J].实用中医内科杂志,2008,22(2):33-34.
[83]MeitesJ.Neuroendoerinology of aging[M].NewYork and London:Pleunm press,2003,23(1):349.
[84]沈自尹,王文健,张玲娟.从肾阳虚和老年人的不同反馈模式讨论阴阳学说[J].中西医结合杂志,1996;6(10):628.
[85]Ishunina TA,Swaah DF.Vasopressin and oxytocin neurons of thehuman supraoptic and paraventricular nucleus:size changes in relation to age and sex[J].J Clin Endocrinol Metab 1999;84(12):4637-4644.
[86]Dent GW,Okimoto DK,Smith MA,et al.Tress-induced alterations in corticotropin—releasing hormone and vasopressin gene expression in the paraventricular nucleus during ontogeny[J].Neuroendocrinology,2000;71(6):333-342.
[87]Knepper MA.Am J Physiol,1997;72:F3-F12.
[88]Lee MD,King LS,Agre P[M].Medicine,1997;76:141-156.
[89]Ishibashi K,Sasaki S,Fushimi K,et al.Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells[J].Proc Natl Acad Sci U S A,1994;91(14):6269-6273.
[90]King LS,Yasui M,Agre P.Molecul Med Today,2000;6:60-65.
[91]Frokiaer J,Marple D,Knepper MA,et al.Am J MedSci,1998;316:291-299.
[92]Marples D,Christensen S,Christensen EI et al.Lithium-induced down-regulation of aquaporin2 water channel expression in rat kidney medulla[J].Clin Invest,1995;95:1838.
[93]Sands J M,Naruse M,Jacobs JD et al.Changes in aquaporin2 protein contribute to the urine concentrating defect in rats fed a low protein diet[J].ClinInvest,1996;97:2807.
[94]Marples D,Frokiaer J,Dorup J et al.Hypokalemia- induced down regulation of aquaporin2 water channel expression in rat kidney medulla and cortex[J].ClinInvest,1996;97:1960.
[95]Deen P M,Verdijk M A,Knoers N V et al.Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine[J].Science,1994;264:92.
[96]邓英姿,许顶立,张远慧.尿液中水孔蛋白22的检测及其与肾组织中表达的相关性[J].肾脏病与透析肾移植杂志,1999;8(4):312-314.
[97]Watters JJ,Poulin P,Doras,DM,et al.Sterio hormone regulation of vasopresginergic neurotransmission in the central nervous system[J].Prog Brain Res,1998;119:247-261.
[98]Gabrielsen A,Warberg J.Christensen NJ,et al.Arterial pulsepressure and vasopressin release graded water immersion in humans[J].Am J Physiol Regul Integr Comp Physiol,2000;278(6):1583-1588.
[99]Gulati K,Lall SB.Angiotensin Ⅱ-receptor subtypes characterization and pathophysiological implications[J].Exp Biol,1996;34(2):91-97.
[100]Van de Heijining BJ,Maigret C,Koekkoek-van den herik I,et al.Dynorphin-A and vasopressin release in the rat:a structure-activity study[J].Neuropeptides,1994;(26):371-378.
[101]DeM GW,OKimoto DK.Smith MA,et al.Stress-induced alterations in cortieotropin-releasing honnone and vasopressin gene expression in the paraventricular nucleus during ontogeny[5].Neuroendocrinology,2000;71(6):333-342.
[102]宋波.有关逼尿肌功能的理解和研究[J].临床泌尿外科杂志,2004;19(11):641-642.
[103]吴博威.第二章细胞的基本功能.姚泰.主编.生理学(七年制临床医学等专业用)[M]北京:人民卫生出版社,2001年.
[104]宋波.逼尿肌兴奋性及逼尿肌不稳定[J].第三军医大学学报,2003,25(22)1969-1971
[105]Abrams P.Urodynamics[M].London:Spriger Verlag London Limited,1997;233-246.
[106]Groat WC.Anatomy of the central neural pathways controlling the lower urinary tract[J].Eur Urol,1998,34(Suppl 1):2-5.
[107]何地英,瞿颂义.药物对膀胱逼尿肌的影响[J].兰州医学院学报,1996;22(1):27-28.
[108]Bayliss M,Wu C,Newgreen D,et al.A quantitative study of atropine resistant contractile responses in human detrusor smooth muscle,from stable,unstable and obstructed bladders[J].Urol,1999;162(5):1833-1839.
[109]Zhakh BS,Burnstock G,Kennedy C,et al.International union of pharmacology.ⅩⅩⅣ.Current status of the nomenclature and properties of P2X receptors and their subunits[J].Pharmacol Rev,2001,53(1):107-18.
[110]North RA.Molecular physiology of P2X receptors[J].Physiol Rev,2002;82(4):1013-67.
[111]Longhurst P A,Eika B,Leggett R E,et al.Comparison of urinary bladder function in 6 and 24 month male and female rats[J]Urol,1992;148(5):1615-1620.
[112]Gosling J A.Modification of bladder structure in response to outflow obstruction and ageing[J].Eur Urol,1997;32(Suppl 1):9-14.
[113]Nishimoto T,Latifpour J,Wheeler M A,et al.Age-dependent alterationsin beta-adrenergic responsiveness of rat detrusor smooth muscle[J].Urol,1995;153(5):1701-1705.
[114]Saito M,Kondo A,Gotoh M,et al.Age-related changes in the response of the rat urinary bladder to neurotransmitters[J].Neurourol Urodyn,1993;12(2):191-200.
[115]Kageyama S,Fujita K,Suzuki K,et al.Effect of age on the responses of rat bladder detrusor strips to adenosine triphosphate[J].BJU Int,2000:85(7):899-904.
[116]龚国清.小鼠衰老模型研究[J].中国药科大报,1991,22(2):101.
[117]樊新荣,黄贵华,朱文锋.太阴病脾虚寒湿证大鼠模型的建立与机理探讨[J].中华中医药学刊,2008;26(1):58-60.
[118]Somlyo A P,Somlyo A V.Signal transduction and regulation in smooth muscle[J].Nature,1994:372(1):231.
[119]Berridge M.Capacitative calcium entry[J].Biochemical Journal,1995;3(12):1.
[120]Fuller W,Parmar V,Eaton P,et al.Cardiac isehemia causes inhibition of the Na/K ATPase by a labile cytosolic compound whose Production is linked to oxidant stress[J].Cardiovasc Res,2003;57(4):i044-i049.
[121]卢圣栋主编.现代分子生物学实验技术[M].北京:高等教育出版社,1993年。
[122]Landau E H,Jayanthi V R,Oatadaill BM,et al.Loss of elasticity in dysfunctional bladders urodynamic and histochmaical correlation[J].Urol,1994;152(2):702-705.
[123]Ewalt D H,Howard P S,Blyth B,et al.Is lamina propria matrix responsible for normal bladder compliance?[J].Urol,1992;148(2):544-549.
[124]Tekgul S,Yashino K Bagli D et al.Collagen types Ⅰ and Ⅲlocalization by in hybridization and immunohistochemistry in the partially obstruction young rabbit bladder[J].Urol,1996:156(2):582-586.
[125]Ewalt D H,Constantinescn S C,Bellno G,et al.Increased collagen type Ⅲ in the neurogenic non-compliant bladdre[J].Urol,1992;147(2):438-452.
[126]Bylund D B,Eikenberg D C,Hieble J P,et al.International Union of Pharmacology nomenclature of adrenoceptors[J].Pharmacol-Rev,1994;46(2):121-136.
[127]Beech D J.Actions of neurotransmitters and other messengers on Ca2+channels and K+ channels in smooth muscle cells[J].Pharmacol Ther,1997;73(2):91-119.
[128]杨听,宋波,方强等.P2X受体亚型在大鼠逼尿肌不稳定中的作用研究.第三军医大学学报[J].2004;26(8):710-713.
[129]马琳,王伟,高红.P2X受体亚型在新生儿膀肤中的表达及其意义[J].中华小儿外科杂志,2007;3(28):164-165.
[130]董晓华,张丹参,武海霞.衰老动物模型的研究进展及评价[J].河北北方学院学报,2004;21(6):41-43.
[131]陈勤.抗衰老研究试验方法[M].北京:中国医药科技出版社,1996年,第一版.
[132]夏寿首.放射生物学[M].北京:军事医学出版社,1998年,第一版:22-44.
[133]陈友琴,胡新抿,刘鸿莲,幸浩洋.YN-PTOL对衰老模型自由基损伤的保 护作用[J].中国医学物理学杂志,2000;7(1):57-58.
[134]崔英俊,李庆章.滑菇多糖对衰老模型鼠不同时期免疫功能的影响[J].东北农业大学学报,2004;35(2):129-134.
[135]Minako K,Noboru M,Kohji K et al.Abnormal accumulation of luteal bodies in ovaries of the senescence accelerated mouse(SAM)[J].The Journal of Reproduction and Development,2001;47(3):153-164.
[136]Suganuma H,Kaburagi S,Inakuma T et al.Amelioratory effect of dietary ingestion of lycopene and tomato rich inlympene on learning impairment in senescence-accelerated mice(SAMP8)[J].Food science and technology research,2002;8(2),183-187.
[137]韩景献.快速老化模型小白鼠(SAM)的老化诸特征及脑老化研究.陈可冀主编,跨世纪脑科学-老年痴呆发病机理与诊治[M].北京:北京医科大学中国协和医科大学联合出版社,1998年12月.
[138]赵湘媛,张石宁,陈明.β-淀粉样蛋白致大鼠衰老模型及单胺类递质改变[J].脑与神经疾病杂志,2001;9(6):333-335.
[139]魏小龙,张永祥.老年性痴呆动物模型研究进展[J].中国药理学通报,2000;16(4):372-37.
[140]许东晖,黄世亮,梅雪婷等.海星甾醇对AlCl3致急性衰老小鼠记忆障碍的保护作用及其机制[J].中国药理学通报,2000,16(4):432-435.
[141]崔旭,李文彬,张炳烈等.D-半乳糖拟脑老化模型的脂质过氧化机理[J].中国老年学杂志,1998;18(1):38-40.
[142]Song X,Bao M,Ii D et al.Advanced glycation in D-galactose induced mouse aging model[J].Mechanisms of Ageing and Development,1999;108(3):239-251.
[143]马虹,徐镰,田苏平等.不同水温游泳对小鼠行为、记忆和脂质过氧化影响差异的研究[J].中国应用生理学杂志,1999;15(3):222-225.
[144]刘晓秋,李卫东,唐惠琼,连至诚.D-半乳糖衰老大鼠自由基代谢状况分析[J].中国老年学杂志,2001:21(6):456-458.
[145]姜招峰,周翔,杨翰仪.海马及皮层的氧自由基损伤与大鼠学习能力和记忆能力的关系[J].中国行为医学杂志,2001;10(4):286-288.
[146]龚锅清.小鼠衰老模型研究[J].中国药科大学学报.1991,22(2)101-103.
[147]李文彬,韦丰,范明等.D-半乳糖在小鼠上诱导的拟脑老化效应.[J].中国药理学与毒理学杂志,1995;9(2):93-95.
[148]钱小明.吴振国.施志明.等.衰老小鼠组织牛磺酸含量与脂质过氧化损伤 的关系[J].基础医学与临床.1995;15(7):390.
[149]王少康,孙桂菊,张建新等.亚急性衰老动物模型的建立及评价[J].东南大学学报(医学版),2002;21(3):217-220.
[150]原文鹏,张硕峰,沈欣等.尿频康对大、小鼠排尿的抑制作用及药动学实验[J].中国实验方剂学杂志,2000;6(6):18-20.
[151]沈自尹,王文建.中医虚证辩证参考标准[J].中西医结合杂志,1986;6:59.
[152]金锡御,宋波.临床尿动力学[M].北京:人民卫生出版社,2002年,第一版.
[153]何地英,瞿颂义.膀肌逼尿肌的组织及生理学概述[J].西北民族大学学报(自然科学版),2005;26(60):82-85.
[154]李新,宋波,李益人等.M受体及其亚型与逼尿肌功能的关系研究[J].第三军医大学学报,2002;24(2):164-166.
[155]刘南,宋波,金锡御.大鼠低顺应性膀胱中Ⅰ型和Ⅲ型胶原蛋白的基因表达[J].第三军医大学学报,2003;25(5):505-507.
[156]Jluel P,Palea S,Barras M,etal.Functional and morphological modifications of the uirnary bladder in aging female rats[J].Am J Physilo Regul Integr Comp Physiol,2000;278(4):984-972.
[157]Schwiebert E M,Zsembery A.Extracellular ATP as a sigma lingmole cule for epithelial cells[J].Biochim Biophys Acta,2003;1615(1-2):7-32.
[158]Boehm S.Signaling via nucleotide receptors in the sympathetic nervous system[J].Drug News Perspect,2003;16(3):141-148.
[159]North RA,Surprenant A.Pharmacology of cloned P2X receptors[J].Annuual Review of Pharmacology Toxicology,2000;40:563-580.
[160]Khakh B S,Burnstock G,Kennedy C,et al.International union of pharmacology.ⅩⅩⅣ.Current status of the nomenclature and properties of P2X receptors and their subunits[J].Pharmacol Rev,2001;53(1):107-118.
[161]李为兵,方强,杨听等.ATP对正常及DI大鼠离体逼尿肌肌条自发性收缩的影响[J].第三军医大学报,2005;27(14):1459-1462.
[162]李为兵.ATP及其受体P2X参与膀胱感觉的研究进展[J].国际泌尿系统杂志,2006;26(6):782-785.
[163]O'Reilly BA,Kosaka AH,Knight GF.P2X receptors and their role in female idiopathic detrusor instability[J].Urol,2002;167(1):157-164.
[164]Osamn Y.β3-adrenoceptors in human detrusor muscle[J].Urology, 2002;59(suppl 5A):25.
[165]Igawa Y,Takeda H,Yamazaki Yet al.Function and molecule or biological evidence for possible β3-adrenoceptor in the human detrusor muscle[J].Br J Pharmacol,1999,126:819.
[166]曹文峰,宋波,陈昭领等.β3-AR介导逼尿肌舒张信号转导机制的实验研究[J].解放军医学杂志,2004;29(6):516-518.
[167]Seguchi H,Nishimura J,Yinbi Zet al.Expression of β3-adrenoceptors in rat detrusor smooth muscle[J].J Urol,1998:159:2197.
[168]孙则禹.肾上腺素能受体与下尿路症状[J].江苏医药,2005;31(3):214-215.
[169]Krief S,Lonnqvist F,Raimbault S,et al.Tissue distribution of beta 3-adrenergic receptor mRNA in man[J].J CIin Invest,1993;91(1):344-349.
[170]Penelope A.Longhurst M.Pharmacological characterization of β-adreno ceptors mediating relaxation of the rat urinary bladder in vitro[J].Br J Pharmacol,1999;127:1744-1750.
[171]曹文峰,宋波,金锡御等.肾上腺素β受体在大鼠逼尿肌中的表达及功能[J].解放军医学杂志,2003;28(2):137-139.
[172]Nishimoto T,Latifpour J,Wheeler A M,et al.Age dependent alteration in β-adrenergic responsiveness of rat detrusor smooth muscle[J].J Urol,1995;153:1701-1705.