Functional and Immunofluorescence Evaluations of Vascular and Neural Integrities in Urinary Bladder of Streptozotocin-Induced Diabetic Mice
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: To assess functional and structural changes in vascular and neural structures associated with diabetic bladder dysfunction (DBD) in the bladders of streptozotocin (STZ)-induced diabetic mice. Methods: Eight-week-old C57BL/6 mice were injected with STZ at 50 mg/kg daily for 5 consecutive days. Catheters were inserted 12 weeks later, and 5 days after catheter placement bladder functions were assessed by conscious cystometry. Neurovascular and extracellular matrix marker changes in harvested urinary bladders were investigated by immunofluorescent staining. Body weights and fasting and postprandial blood glucose levels were measured 12 weeks after STZ injection. Results: STZ-induced diabetic mice had significantly lower body weights and significantly higher blood glucose levels. Assessment of bladder function in STZ-induced diabetic mice revealed a nearly 3-fold increase in bladder capacity and intercontractile interval compared to controls. However, basal pressure, maximal bladder pressure, and threshold pressure were not significantly different. Morphological and structural analysis showed that STZ-induced diabetic mice had significantly reduced microvascular density in lamina propria (33% of the nondiabetic control values), and severely decreased nerve contents in the detrusor region (42% of the nondiabetic control values). Conclusions: STZ-induced diabetic mice exhibit functional and structural derangements in urinary bladder. The present study provides a foundation and describes a useful means of evaluating the efficacies of therapeutic targets and exploring the detailed mechanism of DBD.
Abstract
Purpose: To assess functional and structural changes in vascular and neural structures associated with diabetic bladder dysfunction (DBD) in the bladders of streptozotocin (STZ)-induced diabetic mice. Methods: Eight-week-old C57BL/6 mice were injected with STZ at 50 mg/kg daily for 5 consecutive days. Catheters were inserted 12 weeks later, and 5 days after catheter placement bladder functions were assessed by conscious cystometry. Neurovascular and extracellular matrix marker changes in harvested urinary bladders were investigated by immunofluorescent staining. Body weights and fasting and postprandial blood glucose levels were measured 12 weeks after STZ injection. Results: STZ-induced diabetic mice had significantly lower body weights and significantly higher blood glucose levels. Assessment of bladder function in STZ-induced diabetic mice revealed a nearly 3-fold increase in bladder capacity and intercontractile interval compared to controls. However, basal pressure, maximal bladder pressure, and threshold pressure were not significantly different. Morphological and structural analysis showed that STZ-induced diabetic mice had significantly reduced microvascular density in lamina propria (33% of the nondiabetic control values), and severely decreased nerve contents in the detrusor region (42% of the nondiabetic control values). Conclusions: STZ-induced diabetic mice exhibit functional and structural derangements in urinary bladder. The present study provides a foundation and describes a useful means of evaluating the efficacies of therapeutic targets and exploring the detailed mechanism of DBD.
참고문헌 (35)
- 유탁근, "The prevalence of lower urinary tract symptoms in population aged 40 years or over, in South Korea", Investigative and Clinical Urology, 59(3), pp.166~176 (2018), 대한비뇨의학회[DOI]
- Brown JS, "Urologic complications of diabetes", Diabetes Care, 28, pp.177~185 (2005)
- Abdulmaged M. Traish, "Impact of Testosterone Deficiency and Testosterone Therapy on Lower Urinary Tract Symptoms in Men with Metabolic Syndrome", The World Journal of Men's Health, 36(3), pp.199~222 (2018), 대한남성과학회
- Yuan Z, "Diabetic cystopathy : a review", J Diabetes, 7, pp.442~447 (2015)
- Daneshgari F, "Diabetic bladder dysfunction: current translational knowledge", J Urol, 182(6 Suppl), pp.S18~S26 (2009)
- Frimodt-Møller C, "Diabetic cystopathy: epidemiology and related disorders", Ann Intern Med, 92(2 Pt 2), pp.318~321 (1980)
- Liu G, "Diabetic bladder dysfunction", Chin Med J(Engl), 127, pp.1357~1364 (2014)
- Andersson KE, "Lamina propria: the functional center of the bladder?", Neurourol Urodyn, 33, pp.9~16 (2014)
- Cheng F, "Layer-dependent role of collagen recruitment during loading of the rat bladder wall", Biomech Model Mechanobiol, 17, pp.403~417 (2018)
- Nguyen Nhat Minh, "Three-Dimensional Reconstruction of Neurovascular Network in Whole Mount Preparations and Thick-Cut Transverse Sections of Mouse Urinary Bladder", The World Journal of Men's Health, 39(1), pp.131~138 (2021), 대한남성과학회[DOI]
- Han X, "Effect of electroacupuncture on bladder dysfunction via regulation of MLC and MLCK phosphorylation in a rat model of type 2 diabetes mellitus", Evid Based Complement Alternat Med, 2021, pp.5558890~ (2021)
- Brown JS, "Diabetic cystopathy--what does it mean", J Urol, 181, pp.13~14 (2009)
- Hindi EA, "Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder", Sci Rep, 11, pp.15529~ (2021)
- Yesilyurt ZE, "Urinary bladder weight and function in a rat model of mild hyperglycemia and its treatment with dapagliflozin", Front Pharmacol, 10, pp.911~ (2019)
- 윤국남, "Pericyte-derived heme-binding protein 1 promotes angiogenesis and improves erectile function in diabetic mice", Investigative and Clinical Urology, 63(4), pp.464~474 (2022), 대한비뇨의학회[DOI]
- Furman BL, "Streptozotocin-induced diabetic models in mice and rats", Curr Protoc, 1, pp.e78~ (2021)
- Jin HR, "Functional and morphologic characterizations of the diabetic mouse corpus cavernosum : comparison of a multiple low-dose and a single high-dose streptozotocin protocols", J Sex Med, 6, pp.3289~3304 (2009)
- Yin Guo Nan, "Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function", Experimental and Molecular Medicine, 54, pp.1~13 (2022), 생화학분자생물학회[DOI]
- Mann-Gow TK, "Evaluating the procedure for performing awake cystometry in a mouse model", J Vis Exp, (123), pp.55588~ (2017)
- Arioglu Inan E, "A systematic review of urinary bladder hypertrophy in experimental diabetes: Part I. streptozotocin-induced rat models", Neurourol Urodyn, 37, pp.1212~1219 (2018)
- Miodoński AJ, "Microvascular architecture of the human urinary bladder wall : a corrosion casting study", Anat Rec, 254, pp.375~381 (1999)
- Alfano M, "The interplay of extracellular matrix and microbiome in urothelial bladder cancer", Nat Rev Urol, 13, pp.77~90 (2016)
- Gabella G, "Lamina propria: the connective tissue of rat urinary bladder mucosa", Neurourol Urodyn, 38, pp.2093~2103 (2019)
- Mahajan PV, "Neurogenic bladder repair using autologous mesenchymal stem cells", Case Rep Urol, 2016, pp.2539320~ (2016)
- Wu L, "Functional and morphological alterations of the urinary bladder in type 2 diabetic FVB(db", db)mice, 2016, pp.30, 778~785
- Naoki Aizawa, "Pathophysiology of the underactive bladder", Investigative and Clinical Urology, 58, pp.82~89 (2017), 대한비뇨의학회[DOI]
- Shen JD, "Review of animal models to study urinary bladder function", Biology(Basel), 10, pp.1316~ (2021)
- Bryda EC, "The Mighty Mouse : the impact of rodents on advances in biomedical research", Mo Med, 110, pp.207~211 (2013)
- Rydell-Törmänen K, "The applicability of mouse models to the study of human disease", Methods Mol Biol, 1940, pp.3~22 (2019)
- Daneshgari F, "Time dependent changes in diabetic cystopathy in rats include compensated and decompensated bladder function", J Urol, 176, pp.380~386 (2006)
- Golbidi S, "Bladder dysfunction in diabetes mellitus", Front Pharmacol, 1, pp.136~ (2010)
- Yang XF, "Timedependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin-induced diabetic mice", Neurourol Urodyn, 38, pp.1266~1277 (2019)
- Yang X, "Effects of Radix Linderae extracts on a mouse model of diabetic bladder dysfunction in later decompensated phase", BMC Complement Altern Med, 19, pp.41~ (2019)
- Klee NS, "Urothelial senescence in the pathophysiology of diabetic bladder dysfunction-a novel hypothesis", Front Surg, 5, pp.72~ (2018)
- Fusco F, "Progressive bladder remodeling due to bladder outlet obstruction : a systematic review of morphological and molecular evidences in humans", BMC Urol, 18, pp.15~ (2018)