糖尿病膀胱功能障碍中逼尿肌时序性改变的机制研究进展

doi:10.3969/j.issn.1003-9198.2026.04.004

摘要/Abstract

摘要： 糖尿病膀胱功能障碍(diabetic bladder dysfunction,DBD)是糖尿病患者泌尿系统最常见的慢性并发症,大约40%~60%的糖尿病患者受DBD困扰,出现不同程度的下尿路症状,主要表现为膀胱充盈感减弱、逼尿肌收缩力障碍、膀胱容量增加及残余尿量增多,严重影响患者生活质量。DBD的病理生理涉及逼尿肌状态异常、尿路上皮功能障碍及神经病变。逼尿肌作为膀胱排空的结构基础,其结构与功能的改变是DBD发生发展的关键。本文聚焦DBD病程中逼尿肌的时序性改变,系统阐述逼尿肌从代偿性高活动到失代偿性低活动的动态演变规律,并深入剖析驱动转变的核心机制:早期表现为以神经递质释放增加、嘌呤能信号通路敏化及钙信号通路增强为主导的代偿;随着病程进展,胰岛素信号通路障碍与脂代谢紊乱驱动平滑肌表型转化;最终,氧化应激全面激活导致逼尿肌不可逆的结构破坏与功能衰竭。

关键词: 糖尿病, 糖尿病膀胱功能障碍, 逼尿肌, 发病机制, 动物模型

Abstract: Diabetic bladder dysfunction (DBD) is the most common chronic complication of diabetes mellitus in urology. Approximately 40%-60% of diabetic patients are troubled by DBD, presenting with varying degrees of lower urinary tract symptoms, mainly including reduced bladder filling sensation, detrusor contractile dysfunction, increased bladder capacity and elevated post-void residual urine volume, which seriously affect patients’ quality of life. The pathophysiology of DBD involves abnormal detrusor status, urothelial dysfunction, and neuropathy. As the structural basis for bladder emptying, changes in the structure and function of the detrusor are key to the occurrence and development of DBD. This review focuses on the time-dependent changes of the detrusor during the course of DBD, systematically expounds the dynamic evolution law from compensatory hyperactivity to decompensated hypoactivity, and deeply analyzes the core mechanisms driving the transition. In the early stage, compensation is dominated by increased neurotransmitter release, sensitization of purinergic signaling pathways and enhancement of calcium signaling pathways; With the progression of the disease, insulin signaling pathway disorders and lipid metabolism disorders drive smooth muscle phenotype transformation; Ultimately, comprehensive activation of oxidative stress leads to irreversible structural damage and functional failure of the detrusor.

Key words: diabetes mellitus, diabetic bladder dysfunction, detrusor, pathogenesis, animal models

中图分类号:

孟繁宇, 丁留成. 糖尿病膀胱功能障碍中逼尿肌时序性改变的机制研究进展[J]. 实用老年医学, 2026, 40(4): 344-349.

MENG Fanyu, DING Liucheng. Advances in the mechanisms of time-dependent changes in detrusor muscle in diabetic bladder dysfunction[J]. Practical Geriatrics, 2026, 40(4): 344-349.

参考文献

[1] MAGLIANO D J, BOYKO E J, IDF Diabetes Atlas Committee. Diabetes Atlas[EB]. 11th ed. Brussels:International Diabetes Federation, 2025.
[2] DANESHGARI F, LIU G, BIRDER L, et al. Diabetic bladder dysfunction:current translational knowledge[J]. J Urol, 2009, 182(6 Suppl):S18-S26.
[3] YU H J, LEE W C, LIU S P, et al. Unrecognized voiding difficulty in female type 2 diabetic patients in the diabetes clinic:a prospective case-control study[J]. Diabetes Care, 2004, 27(4):988-989.
[4] HAO F, LUO S, WANG Y, et al. Risk factors of diabetic bladder dysfunction in patients with type 2 diabetes mellitus:a case-control study in Shenzhen, China[J]. Int Urogynecol J, 2025. DOI:10.1007/s00192-025-06282-z.
[5] POWELL C, GEHRING V. Mechanisms of action for diabetic bladder dysfunction:state of the art[J]. Curr Bladder Dysfunct Rep, 2023, 18(2):173-182.
[6] CHEN H, WU A, ZEIDEL M L, et al. Smooth muscle insulin receptor deletion causes voiding dysfunction:a mechanism for diabetic bladder dysfunction[J]. Diabetes, 2022, 71(10):2197-2208.
[7] LIU G, DANESHGARI F. Diabetic bladder dysfunction[J]. Chin Med J:Engl, 2014,127(7):1357-1364.
[8] LEE W C, WU H P, TAI T Y, et al. Effects of diabetes on female voiding behavior[J]. J Urol, 2004, 172(3):989-992.
[9] LEE W C, WU C C, WU H P, et al. Lower urinary tract symptoms and uroflowmetry in women with type 2 diabetes mellitus with and without bladder dysfunction[J]. Urology, 2007, 69(4):685-690.
[10] LIFFORD K L, CURHAN G C, HU F B, et al. Type 2 diabetes mellitus and risk of developing urinary incontinence[J]. J Am Geriatr Soc, 2005, 53(11):1851-1857.
[11] KLEE N S, MORELAND R S, KENDIG D M. Detrusor contractility to parasympathetic mediators is differentially altered in the compensated and decompensated states of diabetic bladder dysfunction[J]. Am J Physiol Renal Physiol, 2019, 317(2):F388-F398.
[12] DANESHGARI F, LIU G, IMREY P B. Time dependent changes in diabetic cystopathy in rats include compensated and decompensated bladder function[J]. J Urol, 2006, 176(1):380-386.
[13] IZUMI K, KAMIJO T C, OSHIRO T, et al. Time-dependent bladder activity changes in streptozotocin-induced female diabetic rats[J]. Physiol Rep, 2025, 13(4):e70220.
[14] YONO M, LATIFPOUR J, YOSHIDA M, et al. Age-related alterations in the biochemical and functional properties of the bladder in type 2 diabetic GK rats[J]. J Recept Signal Transduct Res, 2005, 25(3):147-157.
[15] YANG K, WANG Q. 50 week ultrasound imaging and ultrastructural abnormalities of bladder after sugar diuresis and diabetes mellitus in rats[J]. Int Urol Nephrol, 2021, 53(10):1995-2005.
[16] 任帅, 于普光, 王强强, 等. 糖尿病大鼠膀胱时间依赖性功能和形态学变化[J]. 中国病理生理杂志, 2023, 39(4):632-638.
[17] 王新民, 薛萌, 赵雷. 糖尿病大鼠膀胱病理变化及胰岛素治疗的影响[J]. 临床与实验病理学杂志, 2009, 25(5):531-534.
[18] CAO N, LV R, GOTOH D, et al. Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment[J]. Int J Med Sci, 2024, 21(6):1144-1154.
[19] 郭文敏, 孙李斌, 王东文. 糖尿病膀胱研究进展[J]. 中国全科医学, 2020, 23(17):2095-2101.
[20] SONG Q X, SUN Y, DENG K, et al. Potential role of oxidative stress in the pathogenesis of diabetic bladder dysfunction[J]. Nat Rev Urol, 2022, 19(10):581-596.
[21] ZHANG Y, ZHANG J, LIU J, et al. Imbalance of bladder neurohomeostasis by Myosin 5a aggravates diabetic cystopathy[J]. Mol Med, 2025, 31(1):91.
[22] KENDIG D M, ETS H K, MORELAND R S. Effect of type II diabetes on male rat bladder contractility[J]. Am J Physiol Renal Physiol, 2016, 310(9):F909-F922.
[23] LEIRIA L O, SOLLON C, CALIXTO M C, et al. Role of PKC and CaV₁_.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice[J]. PLoS One, 2012, 7(11):e48507.
[24] MCKENNEY-DRAKE M L, RODENBECK S D, OWEN M K, et al. Biphasic alterations in coronary smooth muscle Ca²⁺ regulation in a repeat cross-sectional study of coronary artery disease severity in metabolic syndrome[J]. Atherosclerosis, 2016, 249:1-9.
[25] 杨森. 钙库操控的钙离子通道在糖尿病大鼠膀胱收缩功能中作用的实验研究[D]. 太原:山西医科大学, 2017.
[26] 中华医学会糖尿病学分会代谢综合征研究协作组. 中华医学会糖尿病学分会关于代谢综合征的建议[J]. 中华糖尿病杂志, 2004, 12(3):156-161.
[27] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2020年版)(上)[J]. 中国实用内科杂志, 2021, 41(8):668-695.
[28] XIONG Y, ZHANG Y, TAN J, et al. The association between metabolic syndrome and lower urinary tract symptoms suggestive of benign prostatic hyperplasia in aging males:evidence based on propensity score matching[J]. Transl Androl Urol, 2021, 10(1):384-396.
[29] MAULDIN J P, NAGELIN M H, WOJCIK A J, et al. Reduced expression of ATP-binding cassette transporter G1 increases cholesterol accumulation in macrophages of patients with type 2 diabetes mellitus[J]. Circulation, 2008, 117(21):2785-2792.
[30] HALMOS B, LA ROSE A M, METHORST D, et al. SMC Abca1 and Abcg1 deficiency enhances urinary bladder distension but not atherosclerosis[J]. Circ Res, 2025, 136(5):491-507.
[31] WANG D, YUAN X, HU C, et al. Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats[J]. Neurourol Urodyn, 2017, 36(1):65-72.
[32] LUO Z, WU A, ROBSON S, et al. Adiponectin signaling regulates urinary bladder function by blunting smooth muscle purinergic contractility[J]. JCI Insight, 2025, 10(4):e188780.
[33] XUE B, KADEERHAN G, SUN L B, et al. Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy[J]. Sci Rep, 2024, 14(1):837.
[34] ELRASHIDY R A, LIU G. Long-term diabetes causes molecular alterations related to fibrosis and apoptosis in rat urinary bladder[J]. Exp Mol Pathol, 2019, 111:104304.
[35] XUE J, LIU Y, ZHANG S, et al. CGRP protects bladder smooth muscle cells stimulated by high glucose through inhibiting p38 MAPK pathway in vitro[J]. Sci Rep, 2021, 11(1):7643.