良性前列腺增生合并膀胱过度活动症患者膀胱黏膜毒蕈碱型胆碱能受体M_2、M_3亚型的表达及临床意义
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摘要
目的探讨良性前列腺增生(benign prostatic hyperplasia,BPH)合并膀胱过度活动症(overactive bladder,OAB)患者膀胱黏膜毒蕈碱型胆碱能受体(muscarinic cholinergic receptor,M受体)M2、M3亚型表达水平的变化及临床意义。方法分析2012年5月~2013年3月20例BPH患者的国际前列腺症状评分(international prostate syndrome scoring,IPSS)、生活质量评分(quality of life,QOL)、膀胱过度活动症症状评分(OAB syndrome scoring,OABSS)和尿动力学检查。根据OABSS评分结果将其分为BPH组(9例)及BPH并OAB组(11例)。2组均在膀胱镜下钳取膀胱黏膜,经逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)检测M受体M2、M3亚型mRNA的表达水平。M2、M3受体mRNA表达水平采用相对于内参基因mRNA表达的相对值ΔCt值表示。比较2组M2、M3受体表达水平及相关性。结果 M2、M3受体表达的ΔCt值BPH组明显低于BPH并OAB组(M2的ΔCt值:-0.154±0.641 vs.0.562±0.762,t=-2.241,P=0.038;M3的ΔCt值:2.534±0.816 vs.3.639±1.019,t=-2.630,P=0.017),说明BPH组M2、M3表达水平均高于BPH并OAB组。2组M2∶M3分别为中位数6.5206(2.35~17.33)和7.9447(2.10~23.83)(Z=-1.102,P=0.271)。同组比较,2组M2表达水平均高于M3(t=-7.776,P=0.000;t=-8.018,P=0.000)。M3表达水平与OABSS和QOL评分呈负相关(r=-0.466,P=0.039;r=-0.496,P=0.026)。结论 BPH合并OAB症状的患者,其膀胱黏膜M2、M3表达水平下降,且M2∶M3比例在合并OAB后有升高的趋势,在OAB发病中起一定作用。M3表达的下降,加重了OAB的程度,降低了患者的生活质量。
Objective To investigate the changes and significance of the expression of the M2 and M3receptors of the urinary bladder mucosa in patients with benign prostatic hyperplasia(BPH) and overactive bladder(OAB). Methods From May 2012 to February 2013,20 cases of BPH were studied on the International Prostate Syndrome Scoring(IPSS),Quality Of Life(QOL),OAB syndrome scoring(OABSS),and urodynamics. According to OABSS results,the patients were divided into either BPH group(n = 9)or BPH and OAB group(n = 11). Mucosa biopsies under the cystoscopy were performed in all the cases. The expression of M2& M3 receptors was assayed by reverse transcription-polymerase chain reaction( RT-PCR). The mRNA expression levels of M2& M3 receptors were indicated by the ΔCt values. Results The levels of ΔCt of M2& M3 receptors were significantly lower in the BPH group than those in the BPH + OAB group,respectively [M2:(-0.154 ±0.641) vs.(0.562 ±0.762),t =-2.241,P =0.038;M3:(2.534 ±0.816) vs.(3.639 ±1.019),t =-2.630,P =0.017],which implied that the expression of M2 and M3receptors was higher in the BPH group than that in the BPH + OAB group. The median ratios of M2∶ M3 in both groups were respectively 6. 5206(2.35-17.33) and 7.9447(2.10-23.83)(Z =-1.102,P =0.271). In the same group,the expression of M2 was higher than M3 in both groups(t =- 7. 776,P = 0. 000; t =- 8. 018,P = 0. 000). The expression of M3 receptors was negatively correlated to OABSS(r =- 0. 466,P = 0. 039) and QOL(r =- 0. 496,P = 0. 026). Conclusions The expression of M2 and M3receptors is decreased and the ratio of M2∶ M3 is increased in patients with BPH and OAB,which may play an important role in the development of OAB. The decreasing of expression of M3 receptor exacerbates the OAB degree and reduces the quality of patients' life.
Objective To investigate the changes and significance of the expression of the M2 and M3receptors of the urinary bladder mucosa in patients with benign prostatic hyperplasia(BPH) and overactive bladder(OAB). Methods From May 2012 to February 2013,20 cases of BPH were studied on the International Prostate Syndrome Scoring(IPSS),Quality Of Life(QOL),OAB syndrome scoring(OABSS),and urodynamics. According to OABSS results,the patients were divided into either BPH group(n = 9)or BPH and OAB group(n = 11). Mucosa biopsies under the cystoscopy were performed in all the cases. The expression of M2& M3 receptors was assayed by reverse transcription-polymerase chain reaction( RT-PCR). The mRNA expression levels of M2& M3 receptors were indicated by the ΔCt values. Results The levels of ΔCt of M2& M3 receptors were significantly lower in the BPH group than those in the BPH + OAB group,respectively [M2:(-0.154 ±0.641) vs.(0.562 ±0.762),t =-2.241,P =0.038;M3:(2.534 ±0.816) vs.(3.639 ±1.019),t =-2.630,P =0.017],which implied that the expression of M2 and M3receptors was higher in the BPH group than that in the BPH + OAB group. The median ratios of M2∶ M3 in both groups were respectively 6. 5206(2.35-17.33) and 7.9447(2.10-23.83)(Z =-1.102,P =0.271). In the same group,the expression of M2 was higher than M3 in both groups(t =- 7. 776,P = 0. 000; t =- 8. 018,P = 0. 000). The expression of M3 receptors was negatively correlated to OABSS(r =- 0. 466,P = 0. 039) and QOL(r =- 0. 496,P = 0. 026). Conclusions The expression of M2 and M3receptors is decreased and the ratio of M2∶ M3 is increased in patients with BPH and OAB,which may play an important role in the development of OAB. The decreasing of expression of M3 receptor exacerbates the OAB degree and reduces the quality of patients' life.
引文
1 Blaivas JG,Marks BK,Weiss JP,et al.Differential diagnosis of overactive bladder in men.J Urol,2009,182(6):2814-2817.
2 Cho MC,Kim HS,Lee CJ,et al.Influence of detrusor overactivity on storage symptoms following potassium-titanyl-phosphate photoselective vaporization of the prostate.Urology,2010,75(6):1460-1466.
3 Daniel G,Gunnar T.Muscarinic receptor subtypes in the lower urinary tract.Pharmacology.2009,83(5):259-269.
4 那彦群,叶章群,孙光,等.中国泌尿外科疾病诊断治疗指南.北京:人民卫生出版社,2011.122-124.
5 Homma Y,Yoshida M,Seki N,et al.Symptom assessment tool for overactive bladder syndrome Overactive bladder symptom score.Urology,2006,68(2):318-323.
6 Malaeb BS,Yu X,McBean AM,et al.National trends in surgical therapy for benign prostatic hyperplasia in the United States(2000-2008).Urology,2012,79(5):1111-1116.
7 Pinto F,Racioppi M,Sacco E,et al.Progression,risk factors and subsequent medical management of symptomatic benign prostatic hyperplasia.Arch Ital Urol ndrol,2009,81(1):1-8.
8 彭浩.前列腺电切术后膀胱过度活动症的药物疗效观察.中国实用医药,2011,6(1):69-70.
9 Michel MC.The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction alpha-blockers in the treatment of male voiding dysfunction-how do they work and why they differ in tolerability.J Pharmacol Sci,2010,112(1):151-157.
10 Andersson KE,Yoshida M.Antimuscarinics and the overactive detrusor-which is the main mechanism of action?Eur Urol,2003,43(1):1-5.
11 Bschleipfer T,Schukowski K,Weidner W,et al.Expression and distribution of cholinergic receptors in the human urothelium.Life Sci,2007,80(24-25):2303-2307.
12 Mansfield KJ,Liu L,Mitchelson FJ,et al.Muscarinic receptor subtypes in human bladder detrusor and mucosa,studied by radioligand binding and quantitative competitive RT-PCR:changes in ageing.Br J Pharmacol,2005,144(8):1089-1099.
13 Chaiyaprasithi B,Mang CF,Kilbinger H,et al.Inhibition of human detrusor contraction by a urothelium derived factor.J Urol,2003,170(5):1897-1900.
14 Andersson KE.Bladder activation:afferent mechanisms.Urology,2002,59(5 Suppl 1):43-50.
15 Matsumoto Y,Miyazato M,Furuta A,et al.Differential roles of M2and M3 muscarinic receptor subtypes in modulation of bladder activity in rats.Urology,2010,75(4):862-867.
16 Kullmann FA,Artim DE,Birder LA,et al.Activation of muscarinic receptors in rat bladder sensory pathways alters reflex bladder activity.J Neurosci,2008,28(8):1977-1987.
2 Cho MC,Kim HS,Lee CJ,et al.Influence of detrusor overactivity on storage symptoms following potassium-titanyl-phosphate photoselective vaporization of the prostate.Urology,2010,75(6):1460-1466.
3 Daniel G,Gunnar T.Muscarinic receptor subtypes in the lower urinary tract.Pharmacology.2009,83(5):259-269.
4 那彦群,叶章群,孙光,等.中国泌尿外科疾病诊断治疗指南.北京:人民卫生出版社,2011.122-124.
5 Homma Y,Yoshida M,Seki N,et al.Symptom assessment tool for overactive bladder syndrome Overactive bladder symptom score.Urology,2006,68(2):318-323.
6 Malaeb BS,Yu X,McBean AM,et al.National trends in surgical therapy for benign prostatic hyperplasia in the United States(2000-2008).Urology,2012,79(5):1111-1116.
7 Pinto F,Racioppi M,Sacco E,et al.Progression,risk factors and subsequent medical management of symptomatic benign prostatic hyperplasia.Arch Ital Urol ndrol,2009,81(1):1-8.
8 彭浩.前列腺电切术后膀胱过度活动症的药物疗效观察.中国实用医药,2011,6(1):69-70.
9 Michel MC.The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction alpha-blockers in the treatment of male voiding dysfunction-how do they work and why they differ in tolerability.J Pharmacol Sci,2010,112(1):151-157.
10 Andersson KE,Yoshida M.Antimuscarinics and the overactive detrusor-which is the main mechanism of action?Eur Urol,2003,43(1):1-5.
11 Bschleipfer T,Schukowski K,Weidner W,et al.Expression and distribution of cholinergic receptors in the human urothelium.Life Sci,2007,80(24-25):2303-2307.
12 Mansfield KJ,Liu L,Mitchelson FJ,et al.Muscarinic receptor subtypes in human bladder detrusor and mucosa,studied by radioligand binding and quantitative competitive RT-PCR:changes in ageing.Br J Pharmacol,2005,144(8):1089-1099.
13 Chaiyaprasithi B,Mang CF,Kilbinger H,et al.Inhibition of human detrusor contraction by a urothelium derived factor.J Urol,2003,170(5):1897-1900.
14 Andersson KE.Bladder activation:afferent mechanisms.Urology,2002,59(5 Suppl 1):43-50.
15 Matsumoto Y,Miyazato M,Furuta A,et al.Differential roles of M2and M3 muscarinic receptor subtypes in modulation of bladder activity in rats.Urology,2010,75(4):862-867.
16 Kullmann FA,Artim DE,Birder LA,et al.Activation of muscarinic receptors in rat bladder sensory pathways alters reflex bladder activity.J Neurosci,2008,28(8):1977-1987.