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Objective At present,there is still a lack of effective means for the treatment of diabetic cystopathy,and to find natural antioxidants for this purpose has become a hot spot in research. This study is to investigate the protective effect of inosine on the bladder of diabetic rats and its antioxidative stress mechanisms. Methods A total of 60 adult male Sprague-Dawley rats were ran-domly divided into three groups of equal number:normal control,diabetes mellitus(DM) model control,and inosine intervention. The DM model was made by intraperitoneal injection of streptozotocin at 60 mg/kg. The DM model controls were injected with saline while the model rats in the intervention group with inosine, all at 75 mg/kg, ip,bid. After 4 and 8 weeks of treatment, the bladder tissues were collected from the rats for examination of the structural changes by HE staining,determination of the expressions of c-kit and nerve growth factor (NGF) by immunofluorescence assay, and observation of the ultrastructure of the bladder tissue under the electron microscope,de-tection of the cell apoptosis by TUNEL,and measurement of the con-tents of malondialdehyde (MDA),superoxide dismutase (SOD),and glutathione (GSH). Results HE staining indicated signifi-cant mucosal hyperplasia, disordered arrangement, loose structure, fracture, expanded intervals and collagen fiber filling of muscle bundles,muscular atrophy,lymphocytes infiltration,vascular hyperplasia and congestion,and few muscle bundles,while electron mi-croscopy manifested disordered arrangement, interrupted connection, mitochondrial vacuolation in muscular and interstitial cells, shrinkage of nuclear membrane,disappearance of nucleoli,and irregular chromatin margination and condensation in the bladder tissues of the DM rat models. Immunofluorescence assay showed that the signals of c-kit and NGF were reduced in the DM models as compared with those in the normal controls. After 4 and 8 weeks of intervention,the cell apoptosis rate was significantly higher in the DM model control ([1.68±3.04]% and [10.51±0.90]%) and inosine-treated rats ([7.00±1.72]% and [7.24±1.66]%) than in the normal controls ([4.65±3.04]% and[5.48±2.00]%),but remarkably lower in the inosine-treated than in the DM model controls(P<0.01). The contents of SOD and GSH were increased(P<0.05) while that of MDA decreased markedly in the DM models(P<0.05),but the former decreased (P<0.05) while the latter increased significantly in the inosine intervention group as compared with the DM model control group (P<0.05). At 8 weeks,the contents of SOD and GSH were remarkably lower in the DM model than in the normal con-trols (P<0.01),while that of MDA markedly higher than in both the normal control and inosine intervention groups (P<0.01). The wet weight of the bladder was significantly increased in the DM model and inosine intervention groups in comparison with that of the nor-mal controls(P<0.01). Conclusion Oxidative stress plays an important role in the development and progression of diabetic cystopa-thy. Inosine can protect the bladder structure and function of the DM rat by reducing oxidative stress and injury to the bladder tissue.
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Diabetic cystopathy is one of the most common complications caused by diabetes in urinary system.There were no obvious clinical manifestations in the early stage of the disease.With the progress of the disease, various complicated lower urinary tract symptoms appeared gradually.All these clinical manifestations cause grate trouble in the health and the quality of life of patients.However, its pathogenesis is not clear, myogenic and neurogenic is the main theory of its pathogenesis.Some studies indicate that long-term consumption of caffeine can reduce the incidence of it, and this article will discuss the cause of this disease and the treatment of caffeine in order to guide clinical practice.
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The etiology and pathogen of diabetic cystopathy is mainly due to qi deficiency of spleen and kidney, which leads to bladder and Sanjiao hypo-function of vital energy, losing opening and closing. In addition to blood stasis injury essence, it blocks the urinary tract. The main pathogen is qi deficiency and blood stasis. The qi deficiency of spleen and kidney is the fundamental aspect, while the blood stasis is the surface aspect. Excess resulted from deficiency, intermingled deficiency and excess, belong to asthenia in origin and asthenia in superficiality. Clinical application of method of invigorating qi, removing blood stasis and eliminating stagnation for diabetic cystopathy has a good clinical efficacy.
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Objective To explore the relationship between the expression of nerve growth factor (NGF) in bladder tissue of Sprague-Dawley rats with diabetes mellitus and the changes of bladder structure and urodynamics.Methods Sixty-three Sprague-Dawley rats were selected and divided into diabetic group (n =33) and control group (n =30).The diabetes mellitus model was made by injecting of steptozotocin (STZ) into the tail vein of rats in the diabetic group;the rats in control group were injected the same volume of citrate buffer solution.The 24 h urinary volume was detected by using metabolic cage;the function of bladder was detected by using Medlab bio-signal collection system;the expression of NGF in the bladder tissue of rats was detected by Western blot;the bladder structure was observed by using light microscope and transmission electron microscope (TEM).Results Four,eight and twelve weeks after the success of diabetic rat model,the level of blood glucose of rats in diabetic group was significantly higher than those in the control group (P ＜ 0.05);the body weight of rats in diabetic group was significantly lower than that in the control group (P ＜ 0.05).The 24 h urinary volume of rats in diabetic group was significantly increased compared with control group (P ＜ 0.05).The maximum capacity of bladder and residual urine volume of bladder and elasticity of bladder of rats in diabetic group were significantly higher than those in the control group (P ＜ 0.05);the maximum bladder pressure of rats in diabetic group was significantly lower than that in the control group (P ＜ 0.05);and the changes of all above indexes of rats in diabetic group were time-dependent(P ＜ 0.05).The expression of NGF in bladder tissues of rats in diabetic group was significantly lower than that in the control group (P ＜ 0.05),and the change of NGF expression in diabetic group was time-dependent (P ＜ O.05).In diabetic group,the bladder smooth muscle was hypertrophic,the organization of smooth muscle was diverse and lose,and the muscle bundle fracture was observed;in control group,the bladder smooth muscle arranged orderly,and the shape was consistent,the structure of fascicle was compact.The condensation and margination of nuclear chromatin and mitochondria swelling were observed in diabetic group;while the bladder tissues in control group showed homogeneous nuclear and mitochondria without fracture and swelling.Conclusion The decrease of the expression of NGF in bladder tissues of diabetic rats can decrease the systolic function of bladder and change the morphology of detrusor and these changes show a time dependence.
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AIM To investigate the improving effect of Suoquan Capsules (Linderae Radix,Alpiniae oxyphyllae Fructus and Dioscoreae Rhizoma) on mice with diabetic cystopathy and its mechanism of action.METHODS Sixty mice were randomly assigned into normal group (n =8) and model group (n =52);the diabetic models of the latter were induced by high-fat feeding combined with streptozotocin (STZ) injection,then modeled mice (n =32) were randomly divided into model,Mecobalamin Tablets,low-and high-dose Suoquan Capsules groups.The influences of Suoquan Capsules on fasting blood glucose (FBG),glycated serum protein (GSP) level and general conditions were observed.The bladder leak point pressure (BLPP) was determined.Histopathological staining was performed on urinary bladder.And the expressions of substance P and NK1 receptor were detected by double immunofluorescent staining.RESULTS There were no significant differences in FBG,GSP,body weight,food intake and water consumption among various groups.The high-dose Suoquan Capsules significantly decreased urine volume of mice.Compared with the model group,the treatment with Suoquan Capsules markedly increased BLPP,the expressions of substance P and NK1 receptor were significantly increased,and the histopathology of bladder in mice was obviously improved.CONCLUSION Suoquan Capsules improves the diabetic cystopathy in mice,and its mechanism maybe related to the up-regulation of substance P and NK1 receptor expressions in bladder tissue.
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Objective Little is known about the effects of antioxidant on the micturition function in diabetic cystopathy .In this study, we investigated the effects of antioxidant sulforaphane on bladder micturition function in diabetes mellitus ( DM)mice with bladder underactivity . Met hods We established DM models in mice by intraperitoneal injection of a single dose of streptozotocin (STZ)at 65 mg/kg and randomly divided them into three groups , sulforaphane treatment (n=10), vehicle treatment (n=10), and DM model (n=10), with another 10 normal healthy mice included as blank controls.At 24 weeks of the experiment, we obtained and analyzed such indexes of mice as the body weight , fasting blood glucose (FBG), 24-hour urine volume (24 h UV) and bladder wet weight ( BWW ) , results of cystometrography , and cystometric parameters including intercontraction interval ( ICI ) , maximum bladder pressure during micturition ( Pmax ) , maximum cystometric capacity (MCC), void volume (VV), post-void residual urine vol-ume (PVR) and residual urine rate (RUR). Results Compared with the blank controls , the DM models with bladder underactivity showed significantly increases in BWW ([67.96 ±2.35]mg), 24 h HU ([22.47 ±1.93]mL), MCC ([0.70 ±0.03]mL), VV (0[.23 ±0.01]mL), PVR ([0.49 ±0.02]mL), RUR ([70.10 ± 0.80]%), and ICI, but a remarkable decrease in Pmax .Sulforaphane treatment significantly reduced BWW ([576.9 ±2.41]mg), 24 h HU ([16.27 ±1.51] mL), MCC ([0.54 ±0.03]mL), PVR ([0.34 ±0.02]mL), RUR ([62.71 ±1.26]%), and ICI of the diabetic mice . Conclusion Sulforaphane could improve bladder micturition function in mice with STZ-induced DM , which might be related to its action mechanism of antioxidative stress damage .
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This study was aimed to explore the curative effect of Zhuo-Du-Qing (ZDQ) particles on diabetic cystopa-thy (DCP) based on the theory of turbid toxin. A total of 100 DCP patients were randomly divided into the control group with 47 cases and the treatment group with 53 cases. Mecobalamin tablets was given in the control group. And ZDQ particles were given to the treatment group. The treatment course was 3 months. The observation was made on the bladder residual urine (BRU), clinical manifestation integral, hemodynamic indexes, HOMA-IR and HbA1c before and after the treatment. The results showed that compared with pretreatment, the BRU, clinical manifestation integral, hemodynamic indexes, and HOMA-IR were significantly reduced (P < 0.01). Compared with the control group, the BRU, clinical manifestation integral, hemodynamic indexes, and HOMA-IR were also significantly reduced (P <0.01). The effective rate in the treatment group was 81.1%, which was significantly higher than 59.6% in the control group (P< 0.05). There were no obvious changes on the blood routine examination, urine routine examination, stool routine examination, liver function, renal function, electrocardiogram and so on before and after treatment. It was con-cluded that the treatment of DCP with ZDQ particles was safe and effective. To remove toxin and descend turbid may be another effective treatment method for DCP. The occurrence and development of DCP were closely related to the turbid toxin.
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AIM: To determine the expression of c-kit mRNA and protein in the bladders in guinea pigs with diabetic cystopathy (DCP) and to explore the correlation and mechanisms between c-kit expression and DCP. METHODS: Sixty guinea pigs were divided randomly into control group (n=20) and experimental group (n=40). The guinea pigs in experimental group were injected with streptozotocin (STZ) to induce diabetes mellitus. After fed for 10 weeks, the animals in both groups were tested with urodynamics, and the guinea pigs in experimental group were divided into the subgroups of DCP and the diabetic no-cystopathy (NDCP) group according to the results of urodynamics. mRNA expression of c-kit was detected by reverse transcription polymerase chain reaction (RT-PCR) and protein expression of c-kit was tested and analyzed by laser scanning confocal microscope. RESULTS: Decreased expression of c-kit mRNA was observed in DCP group compared to control and the NDCP group. The ratio of c-kit mRNA and GAPDH was 5.66±0.54 in controls (P<0.05), 5.54±1.28 in NDCP group (P<0.05) and 4.65 ±0.47 in DCP group. c-kit protein expression significantly declined in DCP group. The mean value of fluorescence intensity was 856.52± 53.03 in control group, 844.67± 59.24 in NDCP group and 548.69± 48.51 in DCP (P<0.01).CONCLUSION: The declined expression of c-kit) gene at transcription and translation levels destroys the SCF/c-kit signal pathway, leading to the dysfunction of Cajal-like) cells in DCP guinea pig, so the abnormal expression of c-kit gene is involved in the pathogenesis of DCP.
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PURPOSE: We have previously demonstrated that increased urethral resistance was more prominent in diabetic rats than in controls. This may result from a compressive obstruction such as damage of the urethral nerve containing nitric oxide. Another possible cause for urethral obstruction could be a constrictive obstruction such as a periurethral fibrosis. In the present study, we investigated the changes in the expression of nitric oxide synthase(NOS) isoforms(compressive obstruction) and collagen subtypes (constrictive obstruction) in the urethral tissues of non-insulin dependent diabetic rats. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats(18 diabetic rats and 18 control rats), bred from birth, were included in this study. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin(90mg/kg) on the second day after birth. Urethral tissues were harvested at 12, 24 and 36 weeks after induction of diabetes and were stained for neuronal NOS(nNOS) and Masson trichrome. We also performed reverse transcriptase-polymerase chain reaction or Western blot analysis to evaluate mRNA or protein expression of NOS isoforms and collagen subtypes in the urethral tissues. RESULTS: Immunohistochemical staining and Western blot analysis of nNOS revealed that the immunoreactivity and nNOS expression in the urethra was lower in the diabetic rats than in the controls. The Masson trichrome staining showed that there was urethral fibrosis in the diabetic rats. The mRNA or protein expression of collagen subtypes, especially type I collagen, were higher in the diabetic rat urethra than in the controls. CONCLUSIONS: These data suggest that the increased urethral resistance in diabetic rats may be attributable to a decrease in the urethral nNOS expression and an increase in collagen content. Urethral dysfunction as well as a cystopathy may play an important role in the pathogenesis of diabetes- induced voiding dysfunction. (Korean J Urol 2007;48:1050-1057)
Subject(s)
Animals , Humans , Male , Rats , Blotting, Western , Collagen , Collagen Type I , Diabetes Mellitus , Fibrosis , Neurons , Nitric Oxide Synthase , Nitric Oxide , Parturition , Protein Isoforms , Rats, Sprague-Dawley , RNA, Messenger , Urethra , Urethral ObstructionABSTRACT
Objective To provide experimental basis for further study of the mechanism of urinary storage dysfunction of diabetic cystopathy (DCP). Methods Steptozotocin(STZ) induced and sucrose induced diabetic rats were employed as DCP and diuresis models. Normal rats served as the control. The changes of calcitonin gene related peptide(CGRP) were analyzed by immunocytochemical method and computer assisted image analysis software. Compliance of the whole bladder prepared in vitro was evaluated by bladder irrigation. The messenger molecule cAMP of detrusor relaxation was determined by radioimmunological assay. Results Compared with those in other groups, the CGRP immunoreactive positive nerve fibers and content of this neurotransmitter significantly decreased in the bladder wall, especially in the submucosa. Significantly higher bladder compliance was observed( P
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PURPOSE: Patients with diabetic cystopathy ultimately undergo morphometric and functional changes in their bladder. Therefore, various voiding symptoms such as frequency, nocturia, urgency, hesitancy, retention and weak stream were evaluated. Irritative symptoms usually develop in cases where the prevalence period of diabetes mellitus (DM) is short, and the obstructive symptoms develop in the opposite case. Improving the voiding symptoms might differ according to prevalence period. Therefore, the therapeutic efficacy of the treatment was compared. MATERIALS AND METHODS: One hundred ten patients were divided into three groups according to how long they had suffered from DM, and were treated with medical therapy over a 4 week period: group A (10yrs). The patients were asked to write their subjective symptoms in a voiding diary and a urodynamic study was undertaken. RESULTS: After medical therapy, the frequency, nocturia and urgency in group A had improved to 72%, 77% and 88% respectively (p0.05). In a urodynamic study of group B, the maximum detrusor pressure had increased from 20.3+/-6.7cmH2O to 53.5+/-8.1cmH2O and the post void residuals decreased from 62.3+/-36.4ml to 21.2+/-17.1ml (p0.05). In group C, there was little improvement in the urodynamic study (p>0.05). CONCLUSIONS: The medical therapeutic efficacy for these patients reduces as the DM revalence period is longer.
Subject(s)
Humans , Compliance , Diabetes Mellitus , Nocturia , Prevalence , Rivers , Sensation , Urinary Bladder , UrodynamicsABSTRACT
PURPOSE: In an effort to characterize the complex voiding dysfunction associated with symptomatic diabetic patients, the results of urodynamic studies of diabetic patients were retrospectively analyzed. MATERIALS AND METHODS: We retrospectively reviewed the clinical information, laboratory findings and urodynamic data, of patients with diabetic cystopathy (DCP) (20 males and 40 females) between January 1997 and December 2001. The urodynamic findings were classified as detrusor instability (DI), impaired detrusor contractility (IDC), detrusor areflexia (DA) and normal detrusor contraction (ND). RESULTS: The mean duration of diabetes in irritative symptom group (40%), combined symptom group (26.7%) and obstructive symptom group (33.3%) was 3.4 years, 8.3 years and 15.2 years, respectively (por=7%, 17 were noted in the obstructive symptom group. The urodynamic findings of the 60 diabetic patients were distributed as follows: 22 (36.7%) detrusor instability, 20 (33.3%) impaired detrusor contractility, 16 (26.7%) detrusor areflexia and 2 (3.3%) normal detrusor contraction. CONCLUSIONS: The shorter the duration of diabetes, the more predominant were the signs of irritative symptoms, whereas the longer the duration of diabetes, the more predominant were the obstructive voiding symptoms. The patients with serum HbA1Cor=7% mostly complained of obstructive symptoms.
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Humans , Male , Glycated Hemoglobin , Retrospective Studies , UrodynamicsABSTRACT
Objective To evaluate the bladder functions by urodynamic studies in diabetic patients with lower urinary tract symptoms (LUTS). Methods Urodynamic studies were performed in 42 diabetic patients (24 men and 18 women;age range,38-78 years).The diabetic history of the patients was from 1 month to 25 years. Results Of the 41 cases who underwent all items of urodynamic examination,38 cases (93%) had abnormal findings and 3 (7%),normal.The detrusor was underactive in 14 cases (34%) and areflexia in 10 (24%);BOO was found in 13 (32%).One female patient had stress urinary incontinence. Conclusions There is a high prevalence of bladder dysfunction in diabetic patients with LUTS.It is necessary to perform urodynamic studies in diabetic patients before initiation of therapy,especially in patients who are assigned to undergo bladder and urethral surgery.Preoperative urodynamic studies can contribute to the surgical success rate.
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PURPOSE: To evaluate the urodynamic findings in diabetics complaining of urinary voiding symptoms, the retrospective study was performed. MATERIALS AND METHODS: For 5 years, from Jan. 1992 to Dec. 1997, urodynamic findings on 76 diabetics(49 males and 27 females) with voiding dysfunction were assessed and classified into; 1, detrusor instability, 2, impaired detrusor contractility, 3, detrusor areflexia, 4, indeterminate, 5, normal. Diabetic patients who had diseases of influential potentiality on bladder function were excluded out. A detailed history of diabetes, past and present medical history were reviewed. In addition, a thorough voiding history, urine culture, blood chemistry and physical examination were determinate. Ophthalmic examination by ophthalmologist and sacral reflex arc examination by urologist were also examined. Those with abnormal sacral reflex arc(absent bulbocavernous reflex, lax anal sphincter tone and control) were deemed sacral cord signs positive, and those with intact sacral reflexes were deemed sacral cord signs negative. RESULTS: The urodynamic findings of 76 diabetic patients were distributed into 25(32.9%) detrusor instability 23(30.3%) impaired detrusor contractility, 21 (27.8%) detrusor areflexia, 6(7.9%) indeterminate and 1 (1.3%) normal. Thirty six(47.4%) of them had retinopathy and 27(35.5%) had positive sacral cord sign, those complications took place most frequently in diabetics with detrusor areflexia. CONCLUSIONS: Diabetic cystopathy revealed various patterns of bladder dysfunction, and detrusor areflexia patients showed high incidence of retinopathy and positive sacral cord sign. It is necessary that urodynamic studies should be done in diabetic cystopathy to characterize the treatment of voiding dysfunction.
Subject(s)
Humans , Male , Anal Canal , Chemistry , Incidence , Physical Examination , Reflex , Retrospective Studies , Urinary Bladder , UrodynamicsABSTRACT
Twenty one ratients diagnosed with diabetic cystopathy in Yongdong Severance Hospital for 6 years were analysed for the clinical and urodynamic features. The mean age was 65.4 years (33-83) and females were twice in number when compared to males. The mean duration of diabetes was 9.7 years. The symptoms were urinary retention, residual urine sensation, abdominal straining, hesitancy, interruption, impaired voiding desire, dysuria in order of frequency. Significant bacteriuria was found in 62% of patients and was more frequent in females, In cases with confirmed bacteriuria, 62% of the identified bacteria was E. coli. Diabetic neuropathy was present in 100% and nephropathy in 77%, nephropathy in 43%. In the presence of one complication, there was a tendency for other concurrent complications. In urodynamic study, the residual urine volume, volume at first sensation, maximum intravesical pressure. compliance were larger than in normal persons and loss of reflex detrusor contraction was more frequent which means impaired bladder sensation and detrusor contractility in diabetic cystopathic patients. The age of patients, duration of diabetes, treatment mode of diabetes, level of blood sugar do not influence the severity of diabetic cystopathy Administration of cholinergics and intermittent catheterization showed a high cure rate and was throughout to be a good treatment mode.