Effects of Low-Energy Shockwave Therapy on the Erectile Function and Tissue of a Diabetic Rat Model
Tóm tắt
Low-energy shockwave therapy (LESWT) has been shown to improve erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED). However, the underlying mechanism remains unknown.
The aim of this study is to investigate whether LESWT can ameliorate DM-associated ED in a rat model and examine the associated changes in the erectile tissues.
Newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) for the purpose of tracking endogenous mesenchymal stem cells (MSCs). Eight weeks later, eight of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group), whereas another eight rats were subject to shockwave (SW) treatment (DM+SW group). Each rat in the DM+SW group received 300 shocks at energy level of 0.1 mJ/mm2 and frequency of 120/minute. This procedure was repeated three times a week for 2 weeks. Another 2 weeks later, all 24 rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology.
Erectile function was measured by ICP. Neuronal nitric oxide synthase (nNOS)-positive nerves and the endothelium were examined by immunofluorescence staining. Smooth muscle and MSCs were examined by phalloidin and EdU staining, respectively.
STZ treatment caused a significant decrease in erectile function and in the number of nNOS-positive nerves and in endothelial and smooth muscle contents. These DM-associated deficits were all partially but significantly reversed by LESWT. MSCs (EdU-positive cells) were significantly more numerous in DM+SW than in DM rats.
LESWT can partially ameliorate DM-associated ED by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis. These beneficial effects appear to be mediated by recruitment of endogenous MSCs.
Từ khóa
Tài liệu tham khảo
Litwin, 1998, Health-related quality of life in men with erectile dysfunction, J Gen Intern Med, 13, 159, 10.1046/j.1525-1497.1998.00050.x
Dorsey, 2010, Phosphodiesterase type 5 (PDE5) inhibitors for the treatment of erectile dysfunction, Expert Opin Pharmacother, 11, 1109, 10.1517/14656561003698131
Gruenwald, 2012, Low-intensity extracorporeal shock wave therapy—A novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy, J Sex Med, 9, 259, 10.1111/j.1743-6109.2011.02498.x
Vardi, 2010, Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction, Eur Urol, 58, 243, 10.1016/j.eururo.2010.04.004
Vardi, 2012, Does low intensity extracorporeal shock wave therapy have a physiological effect on erectile function? Short-term results of a randomized, double-blind, sham controlled study, J Urol, 187, 1769, 10.1016/j.juro.2011.12.117
Zimpfer, 2009, Direct epicardial shock wave therapy improves ventricular function and induces angiogenesis in ischemic heart failure, J Thorac Cardiovasc Surg, 137, 963, 10.1016/j.jtcvs.2008.11.006
Fu, 2011, Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: Molecular-cellular and functional assessment, PLoS ONE, 6, e24342, 10.1371/journal.pone.0024342
Nishida, 2004, Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo, Circulation, 110, 3055, 10.1161/01.CIR.0000148849.51177.97
Mittermayr, 2011, Extracorporeal shock wave therapy (ESWT) minimizes ischemic tissue necrosis irrespective of application time and promotes tissue revascularization by stimulating angiogenesis, Ann Surg, 253, 1024, 10.1097/SLA.0b013e3182121d6e
Aicher, 2006, Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: A new modality to increase efficacy of cell therapy in chronic hind limb ischemia, Circulation, 114, 2823, 10.1161/CIRCULATIONAHA.106.628623
Chen, 2004, Recruitment of mesenchymal stem cells and expression of TGF-beta 1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats, J Orthop Res, 22, 526
Lee, 2002, The effect of vascular endothelial growth factor on a rat model of traumatic arteriogenic erectile dysfunction, J Urol, 167, 761, 10.1016/S0022-5347(01)69141-9
Lin, 2002, Intracavernosal injection of vascular endothelial growth factor induces nitric oxide synthase isoforms, BJU Int, 89, 955, 10.1046/j.1464-410X.2002.02792.x
Lin, 2004, Growth factor therapy and neuronal nitric oxide synthase, Int J Impot Res, 16, S38, 10.1038/sj.ijir.3901214
Lin, 2008, Recent advances in andrology-related stem cell research, Asian J Androl, 10, 171, 10.1111/j.1745-7262.2008.00389.x
Lin, 2012, Stem cell therapy for erectile dysfunction: A critical review, Stem Cells Dev, 21, 343, 10.1089/scd.2011.0303
Bickenbach, 1998, Selection and extended growth of murine epidermal stem cells in culture, Exp Cell Res, 244, 184, 10.1006/excr.1998.4163
Lin, 2009, Labeling and tracking of mesenchymal stromal cells with EdU, Cytotherapy, 11, 864, 10.3109/14653240903180084
Lin, 2012, Identification of active and quiescent adipose vascular stromal cells, Cytotherapy, 14, 240, 10.3109/14653249.2011.627918
Zhang, 2012, Label retaining and stem cell marker expression in the developing rat urinary bladder, Urology, 79, 746 e1, 10.1016/j.urology.2011.10.051
Qiu, 2011, Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats, J Sex Med, 8, 427, 10.1111/j.1743-6109.2010.02118.x
Zhou, 2012, Effects of icariside II on improving erectile function in rats with streptozotocin-induced diabetes, J Androl, 33, 832, 10.2164/jandrol.111.015172
Cellek, 2003, Two phases of nitrergic neuropathy in streptozotocin-induced diabetic rats, Diabetes, 52, 2353, 10.2337/diabetes.52.9.2353
Dashwood, 2011, Identification of neuronal nitric oxide synthase (nNOS) in human penis: A potential role of reduced neuronally-derived nitric oxide in erectile dysfunction, Curr Pharm Biotechnol, 12, 1316, 10.2174/138920111798280965
Thorve, 2011, Diabetes-induced erectile dysfunction: Epidemiology, pathophysiology and management, J Diabetes Complications, 25, 129, 10.1016/j.jdiacomp.2010.03.003
Albersen, 2011, Functional, metabolic, and morphologic characteristics of a novel rat model of type 2 diabetes-associated erectile dysfunction, Urology, 78, 476 e1, 10.1016/j.urology.2011.03.024