| ObjectiveNeurogenic urinary tract dysfunction (NUTD) is a common urinary tract disorder, which is caused by neuropathic damage related to urinate. It is basic therapeutic principles that lasting effective protection of upper urinary tract function and improved quality of life. Traditional research shows upper urinary tract deterioration is likely to occur in patients with high urethral losing pressures or elevated intravesical pressures at the time of urethral urinary loss. The primary goal of bladder management in patients with NUTD is to achieve low urine storage pressure, in order to protect upper urinary tract function. Instituting clean intermittent catheterization and anticholinergic therapy or from surgical correction can effectively reduce the pressure within the bladder and improve the bladder capacity and compliance. However, the upper urinary tract deterioration still arose only by removing secondary urodynamic risk factors from lower urinary traction dysfunction, a condition that is poorly understood. Therefore, the NUTD upper urinary tract injury may be also related to primary dysfunction of ureteral after the loss of the neural control except the lower urinary tract secondary urodynamic risk factors. The purpose of this research is to evaluate the function of ureter in the rabbits with NUTD in order to know the primary urodynamic risk factors for reflux upper urinary tract deterioration. Moreover, it is to investigate the mRNA and protein expression of relative ion channel and receptor of calcium mobilization in ureteral smooth muscle cell (USMC) with NUTD by RT-PCR and Western blot including BKcaα and BKcaβ in order to know molecular mechanism of the USMC with NUTD and to provide a new therapeutic approach to effectively prevent reflux upper urinary tract deterioration.Methods1. Thirty healthy Japanese White Rabbits were randomly divided into three groups: Neuropathic Urinary Tract Dysfunction group (NUTD group,n=10), Experimental Control group (EC group, n=10) and Blank Control group (BC group,n=10). With a spinal cord transaction at the sixth lumbar level and the sacral cord destroyed, the NUTD group showed significant nerve damage, acontractile detrusor (ACD) and without vesicoureteral reflux (VUR) through spine MRI examination and video-urodynamic assessment after two weeks. Experimental group was only bite part of spinous process at the same position, exposed spinal cord but not given a transaction, and blank group without any operation.2. Video-urodynamic assessment、the observation of ureter function and morphology were performed at the second month after operation.3. The expression of mRNA and protein of BKca in ureter smooth muscle cell (USMC) were measured among three groups by real-time fluorescent quantitative PCR (RT-PCR) and Western blot after two months.Results1. Acontractile detrusor was still found in all animal models from NUTD group without vesicoureteral reflux. There was no significant difference in urine volume among the three groups[NUTD group:(18.5±3.7)ml,experimental control group: (19.5±2.4)ml,Blank control group:(17.8±3.2) ml].2. However, the peristalsis times of left ureteral in NUTD group (39.0±3.0) were significantly lower than that in experimental control group (44.0±5.0) and blank control group (46.0±4.0,P<0.05);3. There weren’t abnormal changes in ureteral lamina epithelialis、lamina propria and muscular layer under light microscope among NUTD group.4. Compared with blank control group (BKcaα mRNA:1.02±0.21,BKcaβ mRNA:1.03±0.28; BKcaα protein：0.89±0.10；BKcaβ protein：1.03±0.13), the mRNA expressions of BKcaα (2.89±0.67) and BKcaβ (4.59±1.22) were obviously rised in NUTD group (P<0.001), and expressions of BKcaα (1.35±0.32) and BKcaβ (1.47±0.10) protein also significantly increased (P<0.001).Conclusion1. In addition to secondary urodynamic risk factors, ureter primary dysfunction plays a role in its occurrence.2. The ureter dysfunction has been occurred before appearance of vesicoureteral reflux and the pathological abnormal changes under light microscope in the rabbits with NUTD.3. The increasing of expression of BKca level has inhibited the ureteral excitability and contractility, which may play an important role in upper urinary tract dysfunction of the rabbits with NUTD. |
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