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Objective:To investigate the changes in the morphology, structure and function of the bladders and their effects on the upper urinary tract dilatation(UUTD) after lumbosacral nerve transecting in rats.Methods:A total of 45 female SD rats were included, randomly divided into 3 groups with 15 rats in each group. Two groups were performed bilateral lumbar 6(L6) and cauda equina nerve shearing to establish neurogenic bladder(NB) model, which were nerve transected for 4 weeks(NB-4W) group and nerve transected for 12 weeks(NB-12W) group. Another group was performed bilateral L6 nerves and cauda equine exposing but not transecting, which was sham-operation (Sham) group. Cystometry and renal ultrasound examination were performed and rats in each group were killed to collect the kidney and bladder tissues in NB-4W group at 4 weeks, in Sham group and NB-12W group at 12 weeks after operation. HE, Masson staining, immunohistochemical staining and western blot were used to detect histological changes, expression of transforming growth factor-β1(TGF-β1) and α-smooth muscle actin(α-SMA).Results:All rats in NB-4W and NB-12W group showed acontractile detrusor. In the NB-4W and NB-12W group, the maximum cystometric capacity [(5.84±0.33) ml and (3.13±0.35) ml], the detrusor leak point pressure [(25.41±0.86) cm H 2O and (27.36±2.04) cm H 2O] (1 cm H 2O = 0.098 kPa), were significantly higher than those in the Sham group [(0.98±0.14) ml, (7.13±0.90) cm H 2O, both P<0.05]. Compliance in NB-4W group [(0.28±0.21) ml/cm H 2O] and NB-12W group [(0.17±0.12) ml/cm H 2O] were significantly lower than that of the Sham group [(0.34±0.26) ml/cm H 2O], and the compliance of NB-12W group was lower than that of NB-4W group significantly (all P<0.05). HE staining of the bladder showed that the inflammatory cell infiltration was obvious in the NB-4W and NB-12W group. Bladder collagen volume fractions in NB-4W group [(30.5±1.5) %] and NB-12W group [(45.2±3.8) %] were both higher than that of Sham group [(20.7±2.2) %, both P<0.05]. The expression of TGF-β1 and α-SMA in the bladder tissue of NB-4W group were higher than those of sham group, and that of NB-12W group were higher than NB-4W group. In NB-4W group and NB-12W group, 3 (20.0 %) and 7 (46.7 %) rats were found hydronephrosis, respectively. Additionally, HE staining showed that the degree of renal tubule injury and the number of inflammatory cell infiltration in the NB-4W and NB-12W group were higher than those in the Sham group. Masson staining showed that the volume fraction of collagen in kidneys of NB-4W and NB-12W group were (13.1±1.4) % and (21.6±1.9) %, respectively, which were significantly higher than that in sham operation group [(4.6±0.7) %, both P<0.05]. Conclusions:Bilateral L6 + cauda equina nerve transecting can induce NB with hydronephrosis in parts of rats. The degree of bladder fibrosis gradually increased with the time of nerve transection, and the incidence and severity of UUTD also increased with the time of nerve transection.
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Objective:To explore the urodynamic characteristics of bladder function in patients with abnormal urination after radical hysterectomy of cervical cancer.Methods:In a prospective self-controlled study, a total of 84 patients with cervical cancer and clinical stage of ⅠB to ⅡA, meeting the preoperative inclusion criteria in our hospital from January 2016 to June 2018 were enrolled.All patients were tested for urodynamic testing 1 week before and 6 months after surgery.Patient bladder function status was observed and evaluated before and after surgery and urodynamic examination results were analyzed.Results:Of 84 study cases, the 58 patients developed abnormal urination after radical surgery, there were no urination abnormalities in 26 cases.There was no significant difference in age, clinical stage and pathological diagnosis between patients with and without urination abnormalities.Abnormal urination after radical surgery included difficulty in urinating(55%), frequent urination with a feeling of urination not complete(34%), stress urinary incontinence(7%), and urinary incontinence(4%). Among the 26 patients without urination abnormalities after radical surgery, only one case showed an abnormal urodynamic examination(abnormal bladder sensation). In patients without abnormal urination after surgery, differences in the urodynamic examination findings between pre-and post-surgery were not statistically significant(all P> 0.05). At the same time, in all cases of abnormal urination after radical hysterectomy of cervical cancer, 43 patients(74%)with bladder dysfunction had normal urination pattern before operation, but after operation, the urination abnormality required abdominal pressure.Of the patients with bladder dysfunction after surgery, the maximum flow rate(Qmax)was(12.9±10.3)ml/s, the average flow rate(Qave)was(6.0±4.2)ml/s, the voided volume was(148.0±36.8)ml, voiding time was(32.9±22.1)s, maximum flow time was(11.4±5.0)s, postvoid residual urine was(260.2±219.2)ml, maximal detrusor pressure was(12.1±8.9)cmH 2O, bladder compliance was(16.1±4.3)ml/cmH 2O, normal desire to void was(354.5±204.3)ml, maximal capacity was(587.4±152.5)ml, maximum urethral pressure was(97.6±33.1)cmH 2O, maximum urethral closure pressure was(89.9±36.4)cmH 2O, and function urethral length was(29.6±6.5)mm; In comparison, the above indexes-corresponding values at 1 week before surgery were respectively as follows: the Qmax was(25.1±11.4)ml/s, the Qave was(11.4±6.6)ml/s, the voided volume was(318.6±96.4)ml, voiding time was(29.2±18.5)s, maximum flow time was(6.7±3.9)s, postvoid residual urine was(29.9±21.5)ml, maximal detrusor pressure was(31.9±21.4)cmH 2O, bladder compliance was(78.1±33.9)ml/cmH 2O, normal desire to void was(258.2±185.5)ml, maximal capacity was(335.1±124.9)ml, maximum urethral pressure was(96.4±33.9)cm H 2O, maximum urethral closure pressure was(88.5±35.2)cmH 2O, and function urethral length was(37.2±7.2)mm.It can be seen that Qmax, Qave, voided volume, maximum detrusor pressure, bladder compliance, and functional urethral length in patients with abnormal urination are significantly lower after radical hysterectomy of cervical cancer than before the surgery.While, normal desire to void, maximum capacity, maximum flow time, and postvoid residual urine volume were higher after radical hysterectomy than before surgery( P<0.05). In addition, there was no significant difference in voiding time, maximum urethral pressure and maximum urethral closure pressure between pre-and post-operation.Besides, it is worth noting that there was no significant difference in preoperative urodynamic test results between patients without abnormal urination versus patients with abnormal urination( P>0.05), and the difference in urodynamic test results between the two groups is statistically significant( P<0.05). There was no statistically significant difference in abnormal urination and in urodynamic test results between different clinical stages and between different pathological types( P>0.05). Conclusions:The characteristics of urinary dynamics in patients with abnormal urination after radical hysterectomy of cervical cancer are mainly manifested as decreased bladder sensory function and abnormal detrusor function.And the urodynamic test can provide objective clinical indicators for early diagnosis.
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Objective:To investigate changes in the bladder morphological structure and function and the expression of transforming growth factor-beta1 (TGF-β1) pathway-related proteins in the bilateral spinal nerve amputated neurogenic bladder(NB) rat.Methods:A total of 64 female SD rats were included, and 32 of them underwent bilateral spinal nerve L6+ S1 amputation to construct the NB model and the others were used as sham operation controls.Rats in both NB and control groups received bladder cystometry 3, 6, 12, 24 weeks after corresponding operation.Collagen fibers in their bladder tissues were detected by Masson staining and Sirius scarlet staining.TGF-β1, Smad2 and Smad6 proteins were checked by immunohistochemical staining.TGF-β1 receptor Ⅰ protein was measured by Western blot.Results:Bladders in the NB group were instable, with bladder leak point pressure(BLPP) and underactive voiding pressures.The basal pressure [(22.10±2.51), (18.20±1.52), (31.20±2.82), (41.10±3.41) cmH 2O(1 cmH 2O=0.098 kPa)] and bladder volume [(22.30±1.72), (49.10±5.54), (30.30±2.68), (13.50±1.52) mL] of the NB rats at 3, 6, 12 and 24 weeks were significantly higher than those of the sham operation controls[(3.51±0.45) cmH 2O and (0.52±0.04) mL], and the difference were significant(all P<0.05). The bladder size and thickness in the NB group firstly increased (3, 6 weeks) and then decreased (12, 24 weeks), but the bladder weight increased continuously.Masson staining showed disordered fibrous connective tissues, disintegrated layered bla-dder wall, hypertrophied smooth muscle tissues and deposited intramuscular collagen on the nerve-amputated bladder wall.Sirius scarlet staining suggested that 24 weeks after nerve amputation, collagen Ⅲ increased greatly, and the ratio of type Ⅲ/Ⅰ collagen fibers (3.14±0.71) was significantly higher than that in the sham group (0.88±0.21) ( t= 7.48, P<0.01). According to the immunohistochemical staining results, the expressions of TGF-1β and Smad2 increased while the pathway inhibitory protein Smad6 decreased with time in the NB group.Western blot showed that the expression of TGF-β1 receptor Ⅰ in the amputated bladder was 1.3 and 1.6 folds higher than that in the sham group 12 weeks and 24 weeks after operation( t=6.06, 14.45, all P<0.01). Conclusions:In NB rats with bilateral spinal nerve amputated, bladder contraction becomes paralysis, intravesical pressure increases, bladder normal structure disintegrates and the fibrosis pathway TGF-β1/Smads is activated.Therefore, the key step of development of pediatric NB is bladder fibrosis, which should be prevented as early as possibly in the clinical practice.