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基于β-肾上腺素能受体探讨缩泉丸对衰老大鼠膀胱功能的影响。

Effect of Suo Quan Wan on the bladder function of aging rats based on the β-adrenoceptor.

作者信息

Xu Yi-Fei, Liang Zhi-Jian, Kuang Zhao-Jin, Chen Jie-Jun, Wu Jun, Lu Xiang-E, Jiang Wei-Wen, Fan Ping-Long, Tang Li-Yao, Li Yi-Tao, Huang Ping, Cao Hong-Ying

机构信息

Department of Chinese Medicine Pharmacology, School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.

Center for Drug Non-Clinical Evaluation and Research, Guangzhou General Pharmaceutical Research Institute, Guangzhou, Guangdong 510240, P.R. China.

出版信息

Exp Ther Med. 2017 Jun;13(6):3424-3432. doi: 10.3892/etm.2017.4394. Epub 2017 Apr 27.

Abstract

Suo Quan Wan (SQW) has been used to treat lower urinary tract symptoms (LUTS) in elderly patients for hundreds of years in China. β-adrenoceptors (β-ARs), particularly β-adrenoceptor (β-AR), was reported to be important in the bladder dysfunction of the elderly. The present study was conducted to explore the effect of β-AR, and particularly the β-adrenoceptor, in aging rat bladder function and to test the therapeutic effect of SQW on LUTS in an aging rat model based on the β-adrenoceptor. Briefly, the bladder detrusor muscles of young (age, 3 months) and aging (age, 15 months) female rats were separated. A β-AR non-selective agonist, isoprenaline (ISO), subtype β-AR agonist (BRL37344A) and β-AR antagonist (SR59230A) were used to define the tension change of detrusor muscles between young and aging rats . For blank controls, 12 young rats were marked, and 48 aging female rats were randomly divided into four groups as follows: Model, SQW high, SQW middle and SQW low. Following oral administration of SQW for 6 weeks in aging rats, urodynamic and bladder detrusor tests were used to evaluate the therapeutic effect of SQW. The expression of β-AR mRNA was investigated using reverse transcription-quantitative polymerase chain reaction. Using ISO and BRL37344A , maximum relaxation (E), intrinsic activity (IA), and log (50% effective concentration) (PD) were significantly decreased in aging rats compared with that in young rats (P<0.05). Significant changes were also observed in the β-AR antagonist experiment, which blocked ISO-induced relaxation, with significant decreases observed in E, IA and PD, and a significant increase observed in PA for the aging rats compared with the young controls (P<0.05). SQW was demonstrated to enhance bladder control, storage and contraction ability. Furthermore, SQW was able to increase the sensitivity and expression of β-AR in an aging rat. In conclusion, the decrease in β-AR sensitivity in aging rats and the expression resulted in bladder detrusor dysfunction. In addition, the therapeutic effect of SQW against LUTS relies on the former's effect on the urethral sphincter, bladder detrusor and β-AR.

摘要

在中国,缩泉丸(SQW)已被用于治疗老年患者的下尿路症状(LUTS)数百年。据报道,β-肾上腺素能受体(β-ARs),尤其是β-肾上腺素受体(β-AR),在老年人膀胱功能障碍中起重要作用。本研究旨在探讨β-AR,特别是β-肾上腺素受体,在衰老大鼠膀胱功能中的作用,并基于β-肾上腺素受体测试缩泉丸对衰老大鼠模型中LUTS的治疗效果 。简要地说,分离了年轻(3个月龄)和衰老(15个月龄)雌性大鼠的膀胱逼尿肌。使用β-AR非选择性激动剂异丙肾上腺素(ISO)、β-AR亚型激动剂(BRL37344A)和β-AR拮抗剂(SR59230A)来确定年轻和衰老大鼠之间逼尿肌的张力变化。对于空白对照组,标记12只年轻大鼠,将48只衰老雌性大鼠随机分为四组:模型组、缩泉丸高剂量组、缩泉丸中剂量组和缩泉丸低剂量组。在衰老大鼠口服缩泉丸6周后,使用尿动力学和膀胱逼尿肌测试来评估缩泉丸的治疗效果。使用逆转录-定量聚合酶链反应研究β-AR mRNA的表达。与年轻大鼠相比,使用ISO和BRL37344A时,衰老大鼠的最大舒张(E)、内在活性(IA)和对数(50%有效浓度)(PD)显著降低(P<0.05)。在β-AR拮抗剂实验中也观察到显著变化,该实验阻断了ISO诱导的舒张,与年轻对照组相比,衰老大鼠的E、IA和PD显著降低,PA显著增加(P<0.05)。结果表明,缩泉丸可增强膀胱控制、储存和收缩能力。此外,缩泉丸能够增加衰老大鼠中β-AR的敏感性和表达。总之,衰老大鼠中β-AR敏感性和表达的降低导致膀胱逼尿肌功能障碍。此外,缩泉丸对LUTS的治疗效果依赖于其对尿道括约肌、膀胱逼尿肌和β-AR的作用。

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