Urodynamics Variation And Nerve Growth Factor Expression In Patients Of Benign Prostatic Hyperplasia Complicating With Diabetes

Background and Objective:Benign prostatic hyperplasia (BPH) is one of the most commondiseases in aged male. Its incidence has been going up with advancing age.Two groups of clinical symptoms are caused by BPH-bladder irritative symptoms and obstructive symptoms .The bladder imitative symptoms include urinary frequency, urgency, nocturia and urge incontinence. Detrusor instability (DI) is one of major reasons which cause the imitative symptoms. The obstructive symptoms include urinary hesitancy, straining, decreased force of urination, dribbling, urinary retention and overflow incontinence. The damage of contractile function of detrusor muscle is the major reason of these symptoms. Prostatectomy is the main method for the treatment of BPH. Trans-urethra resectoscopy of prostatic(TURP) was more and more popular in abroad for it's slight trauma, easy recovery, and good curative effect . In our clinical practice, some patients symptoms were not erased satisfactorily after TURP . Lots of factors have been found that contribute to it, such as the obstruction of residue of prostatic, impaired detrusor contractility , et al. Within these factors, impaired detrusor contractility caused by BPH complicating with diabetes was concentrated on .Long-standing diabetes can cause bladder dysfunction, which involves autonomic neuropathy leading to functional parasympathetic and possibly sympathetic denervation of the detrusor. Impaired detrusor function results in a lower maximum flow rate for any given level of bladder outletresi stance and can increase post-void residual, even cause over flow .Nerve growth factor(NGF) is the first polypeptide growth factor that ever found. It correlates closely to the survival,transference,growth and differentiation of neurocyte, is one of the most important biotic activator in nervous system. The prima neurons that respond to NGF were sympathetic neuron, some sensory neuron and centre cholinergic neuron . NGF was generated by target tissues of these neurons, ingested by their axon endings, and was necessary for the survival of these neurons. It plays an important role in maintaining the autonomic innervation of many organs. When impairment proceeded in nerves, the average level of NGF and its mRNA in the remote of impairment could be found raising for several times. It is the same in detrusor denervation. There supposed to be a nutrition balance between neurons and the mussel they dominate to maintain the normal function of the mussel. When detrusor denervation proceeded, the balance was destructed, and a recover chain reaction will prim , and NGF is a part of the chain. The increase of NGF in detrusor enhances the sensitive and contractibility of detrusor wihich cause the bladder imitative symptoms, while the deficiency of NGF lead to detrusor weekness.Since diabetes and BPH increase in prevalence with age, it can be expected that a major fraction of patients with BPH concomitantly suffer from diabetes and vice versa. Rare investigations has been reported about bladder-urethra dysfunction in patients of BPH complicating with diabetes. Our present study overviews the urodynamic alteration in patients of diabetes complicating with BPH, and investigates the expression of NGF in detrusor of those patients, and aims to approach the mechanism of lower urinary tract dysfunction in patients of BPH complicating with diabetes.1.The urodynamic alteration in patients of BPH complicating with diabetes1.1 Materials and methods:1.1.1 Patients A total of 421 patients who suffered from BHP were divided into two groups as none diabetes group(363) and diabetes group(58). Then the patients in the diabetes group were divided into peripheral neuropathy(PNP) group(23) and non PNP group(35). The control group contained 15 aged male patients of diabetes without bladder outlet obstruct(BOO).1.1.2 Urodynamic investigationThe uroflowmetry was carried out firstly to get maximum flow rate (Qmax). The catheterization was performed to measure bladder pressure. Saline at 25°C was continuously filled into the bladder at less than 10ml/min. The abdominal pressure was measured through a balloon 8Fr catheter placed in the rectum. Detrusor pressure was calculated by the subtraction the rectal pressure from the intravesical pressure. Then fill the bladder. Children were asked to void when they could not delay it. Maximum bladder capacity (V_max) was measured. Immediately after voiding, post-voided residual urine (PVR) was extracted from bladder. Detrusor instability (DI), post-voiding contraction (PVC) and detrusor-sphicter dyssynergia (DSD) were observed. Maximal detrusor pressure (P_det-max.) is also recorded. The methods, definitions and units conform to the standards proposed by the International Continence Society (ICS), excepted where specially noted. Natural and artificial filling cystometry were performed in present study, respectively. Natural filling was carried out, and then artificial filling cystometry was performed in present research.1.1.3 Statistical analysisThe paired-samples T test was used to compare Q_max,V_max,P_det-max,and PVR between two groups. Chi-square test was used to compare DI. Data are reported as range and mean plus or minus standard deviation, and p<0.05 was considered statistically significant. All calculations were done by SPSS 11.5 statistical software.1.2 ResultsThe Q_max(ml) in all the three observation groups were lower than the control group, the Q_max in the BPH without diabetes group higher than that in the the BPH with diabetes no peripheral neuropathy symptom group and BPH with diabetes peripheral neuropathy symptom group. The V_max in the BPH without diabetes group was lower than the control group while in the two BPH with diabetes sub-groups were all higher than it. The PVR in all the three observation groups were lower than the control group, the PVR in the BPH without diabetes group was fewer than that in the two BPH with diabetes sub-groups. The P_det-max in the BPH without diabetes group was lower than the control group while in the two BPH with diabetes sub-groups were all higher than it. The DI rate in the BPH without diabetes group was higher than the control group while in the two BPH with diabetes sub-groups) were all lower than it. All the differences reached statistical significance. And there was non significant difference between the BPH with diabetes peripheral neuropathy symptom group and the BPH with diabetes no peripheral neuropathy symptom group.2.The expression of NGF in dettrusor of patients of BPH complicating with diabetes2.1 Materials and methods:2.1.1 Patients: The patients who received TURP in each group in the previous essay, and the grouping was retained of as non diabetes group(138), diabetes with peripheral neuropathy(PNP) group(18) and diabetes without PNP group(30).2.1.2 Immunohistochemical study: The immunohistochemical analys for NGF was performed by using streptavidin biotin horseradish peroxidase staining in the control group, the obstructive detrusor stability group and the obstructive detrusor instability group. Replacing the primary antibody with PBS made the negative contrast.The statistical analyses were performed using the software of SPSS 11.5 statistical package. P value less than 0.05 was regarded as significant.2.2 Results:The NGF expression of bladder detrusor in the control group was 40% negative position, 60% weak positive, no moderate and strong positive; 5.1% negative position,49.3% weak positive, 34.8% moderate positive and 10.9% strong positive in the BPH without diabetes group; 72.2% negative position, 27.8% weak positive, no moderate and strong positive in the BPH with diabetes peripheral neuropathy symptom group; 56.7% negative position, 43.3% weak positive, no moderate and strong positive in the BPH with diabetes no peripheral neuropathy symptom group. The expression levels of NGF in the BPH without diabetes group was significantly increased compared with that in the control group, and the two BPH with diabetes groups were significantly reduced compared with that in the control group. All the differences reached statistical significance (P<0.01). And there was non significant difference between the BPH with diabetes peripheral neuropathy symptom group and the BPH with diabetes no peripheral neuropathy symptom group (P>0.05).Conclusions:1. Bladder outlet obstruction(BOO) leads to the increase of micturition resistance, the latter leads to the increase of the expression of NGF in detrusor, and causes the sensitivity of the detrusor increasing. These changes is one of the main causes of the symptoms of the BPH patients.2. The main manifestation of diabetic cystopathy (DC) is the sensitivity and excitability of detrusor reducing, and the efficacy of evacuation depresses. Detrusor innervation disorder caused by the default of NGF is one of the main causes of the dysfunction of DC.3. When BPH complicating with diabetic, BOO and detrusor innervation disorder presence at the same time, the depressing of the efficacy of evacuation is more obviously and the bladder irritating symptom comes less. Detrusor dysfunction may be ignored and it is one of the main causes of the curative effect disaffect after TURP in patients of BPH complicating with diabetic.