Abstract
Previous studies observed have reported that electroacupuncture (EA) is effective in relieving diabetic bladder dysfunction (DBD); however, little is known about the mechanism. Therefore, we explored the effects and mechanisms of EA on DBD in streptozotocin–high-fat diet- (STZ–HFD-) induced diabetic rats. The Sprague-Dawley male rats were divided randomly into four groups: normal group, diabetes mellitus group (DM group), DM with EA treatment group (EA group), and DM with sham EA treatment group (sham EA group). After 8 weeks of EA treatment, the body weight, serum glucose, bladder weight, and cystometrogram were evaluated. The bladder wall thickness was examined by abdominal ultrasound imaging. After the transabdominal ultrasound measurements, hematoxylin-eosin (HE) staining was used to observe the bladder mucosa layer. The bladder detrusor smooth muscle cells (SMCs) and fibroblasts were observed under transmission electron microscopy (TEM). The phospho-myosin light chain (p-MLC), phospho-myosin light chain kinase (p-MLCK), and phospho-myosin phosphatase target subunit 1 (p-MYPT1) levels in the bladder were examined using Western blot. The bladder weight, serum glucose, bladder wall thickness, volume threshold for micturition, and postvoid residual (PVR) volume in the diabetic rats were significantly higher than those in the control animals. EA treatment significantly reduced the bladder weight, bladder wall thickness, volume threshold for micturition, and PVR volume in diabetic rats. EA caused a significant increase in the MLC dephosphorylation and MLCK phosphorylation levels in the group compared to the sham EA and model groups. EA reduced the infiltration of inflammatory cells in the bladder mucosa layer of diabetic rats. In addition, EA repaired the damaged bladder detrusor muscle of diabetic rats by reducing mitochondrial damage of the SMCs and fibroblasts. Therefore, EA could reduce the bladder hypertrophy to ameliorate DBD by reversing the impairment in the mucosa layer and detrusor SMCs, which might be mainly mediated by the regulation of p-MLC and p-MLCK levels.
Highlights
Diabetes mellitus (DM) as a metabolic disease has reached epidemic proportions worldwide and is associated with various complications, including retinopathy, neuropathy, and nephropathy [1]. e global prevalence of diabetes in adults has reached 9.3%; that is, there are already 463 million adult diabetic patients worldwide [2]
Myosin light chain phosphatase (MLCP) activity is associated with mammalian bladder function, and it is speculated that a change in MLC may play an important role in the nervous and myogenic control of the bladder [7]. e function of striated or smooth muscle is regulated by the balance of myosin light chain kinase (MLCK) and MLCP activity
The bladder weight of diabetic rats in the EA group significantly decreased compared to the sham EA group (P < 0.05). ere was no significant difference between the sham EA group and the DM group
Summary
Diabetes mellitus (DM) as a metabolic disease has reached epidemic proportions worldwide and is associated with various complications, including retinopathy, neuropathy, and nephropathy [1]. e global prevalence of diabetes in adults has reached 9.3%; that is, there are already 463 million adult diabetic patients worldwide [2]. Multiple lines of evidence imply that MYPT1 may regulate the biochemical activity of MLCP through multiple mechanisms, thereby regulating MLC phosphorylation and affecting bladder smooth muscle detrusor contraction [14]. Previous studies have revealed the advantages of acupuncture in the treatment of bladder dysfunction, which includes alleviation of symptoms (improvement of chronic urinary retention and incontinence), improvement in the quality of life of patients, and delayed progression of DBD [17]. A related animal study has shown that a 2-Hz EA stimulation at BL33 can enhance the detrusor smooth muscle contraction and improve voiding dysfunction [18]. We propose a hypothesis that the mechanism of EA in the treatment of DBD may be attributed to the regulation of the bladder contraction element and MLC phosphorylation levels to promote detrusor relaxation and improve bladder function. Comprehensive application of cystometrogram, transabdominal ultrasound measurement, hematoxylineosin (HE) staining, transmission electron microscopy (TEM) examination, and Western blot was used to explore the effect of EA on DBD and its possible biological mechanism from different levels of function, morphology, and molecule
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