糖尿病大鼠膀胱重构中M3受体改变的实验研究

目的:研究病程24周的2型糖尿病大鼠膀胱重构时,逼尿肌收缩功能的改变和M3受体含量及其基因转录水平的改变情况,并探讨二者之间的相关性。方法:2d龄雌性Wistar大鼠随机分成实验组和正常对照组,应用链脲佐菌素腹腔注射并结合高糖高脂饮食进行2型糖尿病大鼠动物模型制备。于糖尿病病程24周时进行下列实验:应用离体膀胱灌注方法观察逼尿肌收缩功能的变化;应用RT-PCR和Western blotting方法观察逼尿肌M3受体mRNA和蛋白表达的变化。结果:2型糖尿病组大鼠逼尿肌收缩功能低于正常对照组,为(16.52±2.97)cmH2O/100mgVS(25.66±3.56)cmH2O/100mg;2型糖尿病组大鼠逼尿肌M3受体mRNA和蛋白的表达均高于正常对照组,分别为(65.27±4.61)%VS(37.53±4.02)%和(45.19±2.37)%VS(23.67±2.85)%。结论:本研究证实了2型糖尿病大鼠在病程24周时膀胱逼尿肌的收缩力降低,但M3受体的生物合成却上调,这种不平行现象可能是病变进展的表现,为深入研究糖尿病膀胱病的发病机制提供了有价值     

Calcitriol Improves Streptozotocin-induced Diabetes and Recovers Bone Mineral Density in Diabetic Rats

Vitamin D analogs exert a preventative effect on experimental diabetes, but whether or not they are able to halt progress of established diabetes is not yet known. Moreover, it is widely accepted that diabetes may induce osteoporosis, but the efficacy of vitamin D on diabetic osteoporosis is not clear. In order to help clarify these issues, we have tested the efficacy of calcitriol streptozotocin-induced diabetes. Streptozotocin (60 mg/Kg body weight) was injected in 3-month-old Wistar rats, randomly distributed into two groups: vehicle (olive oil) treated diabetic rats (D) and diabetic rats treated with 1.25-(OH)₂D₃ 250 mg, three times a week (DT). Control animals (C) were treated with vehicle alone. The experiment lasted 8 weeks. The histology of the pancreata was evaluated. Blood gluclose and calcium and phosphate in serum and urine were measured. Finally, bone mineral density (BMD) of tibia and lumbar vertebrae were evaluated. After 8 weeks, diabetes persisted in 85% of the diabetic rats (D group), but in only 45% of vitamin D-treated group (DT). At the end of the experiment, DT animals were separated into two groups, those still remaining diabetic (DT-NR) and reversed animals (DT-R). Moreover, bone loss was observed in diabetic animals (D), whereas BMD of DT-R rats showed similar values to those of controls (C). Our results suggest that 1.25(OH)₂D₃ improves diabetes and, as such, may recover BMD in streptozotocin-induced diabetic rats.     

患糖尿病12周大鼠睾丸生精细胞周期及其凋亡与抗氧化水平的变化

目的:探讨患糖尿病12周大鼠睾丸生精细胞周期及其凋亡和血清与睾丸抗氧化水平的变化。方法:W istar大鼠随机分为正常对照组10只,糖尿病组20只。腹腔注射链佐脲菌素(STZ)建立糖尿病大鼠模型,12周末记录其存活率、体重和睾丸重量;采用流式细胞术检测生精细胞周期各时相细胞百分率和细胞凋亡率,应用硫代巴比妥酸法(TBAR s)、硝酸还原酶法、黄嘌呤氧化酶法、二硫代二硝基苯甲酸法(DTNB)和分光光度法分别检测血清及睾丸丙二醛(MDA)和一氧化氮(NO)含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和NO合酶(NOS)活性。结果:大鼠患糖尿病12周后,其存活率、体重和睾丸重量显著低于正常对照组(P<0.05);G0/G1期生精细胞显著增加(P<0.05),S期和G2/M期细胞减少,即发生了G0/G1期细胞阻滞;生精细胞凋亡率明显增加(P<0.05)。与正常对照组相比,糖尿病大鼠血清和睾丸MDA含量增加,其中后者增加明显(P<0.01);血清及睾丸SOD活性降低;血清GSH-Px活性显著低于对照组(P<0.05),而睾丸GSH-Px活性显著增高(P<0.01);血清和睾丸NO含量增高,尤其前者显著升高(P<0.01);血清NOS活性显著降低(P<0.05)。结论:睾丸组织及血清MDA和NO含量增加,以及抗氧化酶活性降低,可能与糖尿病大鼠生精细胞G0/G1期阻滞和凋亡增多所致生精障碍有关。     

尿毒清颗粒对糖尿病大鼠足细胞损伤的保护作用研究

目的：探讨尿毒清颗粒对糖尿病大鼠足细胞损伤的保护作用。方法：将SD大鼠制备成STZ糖尿病模型,实验分3组：正常对照组、糖尿病未干预组、尿毒清颗粒治疗组（2.6g·kg-1·d-1灌胃）,于实验第4周、8周末检测血糖、血肌酐、尿肌酐及尿白蛋白排泄率,光镜、电镜下观察肾组织病理改变并计数足突宽度,免疫组化观察足细胞相关蛋白分子nepherin、podocin的表达,Real time-PCR检测肾皮质nepherin、podocin mRNA表达。结果：尿毒清颗粒可以改善糖尿病大鼠肌酐清除率,降低尿白蛋白排泄,改善肾脏病理,减轻足突融合,维持足细胞相关蛋白分子的分布与表达。结论：初步证实尿毒清颗粒能通过上调足细胞相关蛋白分子水平减轻足细胞损伤,对糖尿病大鼠足细胞损伤具有保护作用。     

Pioglitazone in the Management of Diabetes Mellitus after Transplantation

Type 2 diabetes mellitus is a common problem in patients after solid organ transplantation. We studied the safety and efficacy of pioglitazone therapy in this setting. Ten patients with diabetes mellitus treated with insulin or glyburide after transplantation were studied after the addition of the thiazolidinedione pioglitazone. Serum creatinine, HBA1C, total daily insulin dose, tacrolimus dose, tacrolimus level and prednisone dose were followed for a mean of 242 days and compared to the corresponding values measured before the initiation of pioglitazone. The addition of pioglitazone caused no significant changes in serum creatinine or mean tacrolimus dose, and caused decreases in HBA1C (8.36%+/- 1.5% pre-pioglitazone, 7.08%+/- 1.5% post-pioglitazone, p = 0.018) and total daily insulin dose (125.1 +/- 28.1 units pre-pioglitazone, 80.6 +/- 22.8 units post-pioglitazone, p = 0.002). Our preliminary study suggests that pioglitazone is a safe and effective oral agent for the management of diabetes mellitus after transplantation.     

Diabetes Mellitus after Kidney Transplantation in the United States

New onset diabetes is a major complication after kidney transplantation. However, the incidence, risk factors and clinical relevance of post-transplant diabetes mellitus (PTDM) vary among reports from single-center observational studies and clinical trials. Using data from the United Renal Data System we identified 11 659 Medicare beneficiaries who received their first kidney transplant in 1996-2000. The cumulative incidence of PTDM was 9.1% (95% confidence interval = 8.6-9.7%), 16.0% (15.3-16.7%), and 24.0% (23.1-24.9%) at 3, 12, and 36 months post-transplant, respectively. Using Cox's proportional hazards analysis, risk factors for PTDM included age, African American race (relative risk = 1.68, range: 1.52-1.85, p < 0.0001), Hispanic ethnicity (1.35, range: 1.19-1.54, p < 0.0001), male donor (1.12, range: 1.03-1.21, p = 0.0090), increasing HLA mismatches, hepatitis C infection (1.33, range: 1.15-1.55, p < 0.0001), body mass index >or=30 kg/m2 (1.73, range: 1.57-1.90, p < 0.0001), and the use of tacrolimus as the initial maintenance immunosuppressive medication (1.53, range: 1.29-1.81, p < 0.0001). Factors that reduced the risk for PTDM included the use of mycophenolate mofetil, azathioprine, younger recipient age, glomerulonephritis as a cause of kidney failure, and a college education. As a time-dependent covariate in Cox analyses that also included multiple other risk factors, PTDM was associated with increased graft failure (1.63, 1.46-1.84, p < 0.0001), death-censored graft failure (1.46, 1.25-1.70, p < 0.0001), and mortality (1.87, 1.60-2.18, p < 0.0001). We conclude that high incidences of PTDM are associated with the type of initial maintenance immunosuppression, race, ethnicity, obesity and hepatitis C infection. It is a strong, independent predictor of graft failure and mortality. Efforts should be made to minimize the risk of this important complication.     

The Changes of Pro-opiomelanocortin Neurons in Type 2 Diabetes Mellitus Rats After Ileal Transposition: The Role of POMC Neurons

Background  

Ileal transposition (IT) can effectively resolve obesity and improve type 2 diabetes. IT is associated with increased glucagon-like peptide 1 secretion. The mechanisms mediating the effects of IT on obesity and diabetes remain undefined. Given the role of pro-opiomelanocortin neurons in energy balance, we sought to determine its potential role in these processes.     

原发性肝癌合并糖尿病手术前后胃泌素和胃动素水平的变化

目的探讨糖尿病对原发性肝癌(HCC)手术治疗前、后胃肠激素水平变化的影响。方法选取2007年4月至2010年2月期间我院收治的择期手术治疗的HCC患者143例,其中合并糖尿病者43例(DM组),不合并糖尿病者100例(NDM组),测定术前3d及术后1、2及7d血胃泌素(GAS)和胃动素(MTL)水平。结果①2组患者术后1、2及7d血浆MTL水平较术前明显下降(P<0.05),血浆GAS水平较术前明显升高(P<0.05)。②与NDM组相比,DM组术前血浆MTL和GAS水平均高于NDM组(P<0.05),术后1、2及7d血浆MTL水平降低更明显(P<0.05),GAS水平升高也更明显(P<0.05)。③NDM组术后首次肛门排气时间明显早于DM组(P<0.05)。④DM组病史≥10年、空腹血糖≥10mmol/L者首次肛门排气时间较病史<10年、空腹血糖<10mmol/L者明显延长(P<0.05)。结论糖尿病影响HCC切除术后的血GAS、MTL水平变化,糖尿病病程长及血糖控制不佳加重术后GAS、MTL水平的变化,使术后胃肠功能恢复延迟。     

胃袖带切除术对GK大鼠2型糖尿病的影响及其机理

目的研究胃袖带切除术（sleevegastrectomy,SG）对GK大鼠2型糖尿病（type2diabetesmellitus,T2DM）的治疗作用及其可能机理。方法将13只12周龄的GK大鼠随机分为2组：SG组7只和假手术组（SO组）6只,分别行SG术和假手术。于术前及术后1、4、10和26周测量2组大鼠的体质量、24h进食量、空腹血糖值、血清胰高血糖素样肽-1（glucagon-likepeptide-1,GLP-1）和血清生长激素释放肽（Ghrelin）浓度;于术后10周检测2组大鼠的粪便能量含量,并进行口服葡萄糖耐量实验（OGTT）和胰岛素耐受性实验（ITT）。结果①体质量：各时点2组大鼠的体质量比较差异均无统计学意义（P〉0．05）;与术前比较,术后1周2组大鼠的体质量均降低（P〈0．01）,术后10和26周的体质量均增加（P〈0．01）。②24h进食量：与SO组比较,术后4和10周SG组大鼠的24h进食量均较低（P〈0。05）。与术前比较,SG组大鼠术后1、4及10周的进食量均较低（P〈0．05）,SO组大鼠术后1周的进食量低于术前（P〈0．05）。③空腹血糖值：与SO组比较,术后各时点SG组大鼠的空腹血糖值均较低（P〈0．01）。与术前比较,SG组大鼠术后各时点的空腹血糖值均较低（P〈0．01）,而SO组大鼠仅术后1周明显低于术前∽〈0．OD。④血清GLP-1水平：与SO组比较,术后4、10及26周SG组大鼠的血清GLP．1水平均较高（P〈0．05）。与术前比较,术后4、10及26周SG组大鼠的血清GLP-1水平较高（P〈0．05）,而术后SO组大鼠的血清GLP．1水平无明显变化（P〉0．05）。⑤血清Ghrelin水平：与SO组比较,术后各时点SG组大鼠的血清Ghrelin水平均较低（P〈0．01）。与术前比较,术后各时点SG组大鼠的血清Ghrelin水平均较低（P〈0．001）,而SO组大鼠的血清Ghrelin水平无明显变化（P〉0．05）。⑥曲线下面积（AUC）：SG组大鼠的AUC（OGTT和ITT）均较SO组低（P〈0．01）。结论SG术可以明显降低GK大鼠的空腹血糖值,改善葡萄糖耐量及增强胰岛素敏感性,该作用可能是GLP．1、Grelin等多种胃肠道激素共同作用的结果。SG术可能是潜在的非肥胖型T2DM的治疗方法。     

Roux-en-Y胃转流术对2型糖尿病大鼠血清vaspin表达的影响

目的研究Roux-en-Y胃转流术(RYGB)对2型糖尿病(T2DM)大鼠的治疗作用,并探讨内脏脂肪组织产生的丝氨酸蛋白酶抑制剂(vaspin)在RYGB治疗T2DM机制中的可能作用。方法取造模成功的T2DM大鼠20只和周龄、性别相匹配的正常SD大鼠20只,用随机数字表法将其随机分为T2DM-RYGB组、T2DM-假手术组及RYGB组、假手术组,每组10只。分别于术前及术后第4和8周检测各组大鼠的空腹血糖(FPG)、血清胰岛素(INS)、血清vaspin水平及胰岛素抵抗指数(HOMA-IR),并分析血清vaspin水平与FPG、INS及HOMA-IR的相关性。结果手术前,T2DM-RYGB组与T2DM-假手术组比较以及RYGB组与假手术组比较,FPG水平、INS水平、vaspin水平及HOMA-IR差异均无统计学意义(P>0.05);而T2DM-RYGB组及T2DM-假手术组的FPG水平、INS水平、vaspin水平及HOMA-IR均分别明显高于RYGB组(P<0.05)及假手术组(P<0.05)。术后第4周,T2DM-RYGB组FPG水平、INS水平、vaspin水平及HOMA-IR较术前下降,除FPG水平(P<0.05)外,其余指标与术前比较差异均无统计学意义(P>0.05);术后第8周,FPG水平、INS水平、vaspin水平及HOMA-IR进一步下降,与术前比较差异均有统计学意义(P<0.05)。T2DM-假手术组、RYGB组及假手术组组内术前及术后第4周、第8周FPG水平、INS水平、vaspin水平及HOMA-IR比较,差异均无统计学意义(P>0.05)。手术前及手术后第4周、第8周T2DM-RYGB组与T2DM-假手术组血清vaspin水平与其对应血清INS水平、HOMA-IR均呈正相关(P<0.05)。结论 RYGB对T2DM大鼠具有一定的治疗作用,RYGB后vaspin表达水平降低,胰岛素敏感性改善,这可能是RYGB治疗T2DM的机制之一。     

Incidence of and Risk Factors for Posttransplant Diabetes Mellitus after Pancreas Transplantation

Posttransplant diabetes mellitus (PTDM) after pancreas transplantation (PTX) has not been extensively examined. This single center, retrospective analysis of 674 recipients from 1994 to 2005 examines the incidence of and risk factors for PTDM after PTX. PTDM was defined by fasting plasma glucose level ≥126 mg/dL, confirmed on a subsequent measurement or treatment with insulin or oral hypoglycemic agent for ≥30 days. The incidence of PTDM was 14%, 17% and 25% at 3, 5 and 10 years after PTX, respectively and was higher (p = 0.01) in solitary pancreas (PAN) versus simultaneous kidney pancreas (SPK) recipients (mean follow‐up 6.5 years). In multivariate analysis, factors associated with PTDM were: older donor age (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.03–1.06, p < 0.001), higher recipient body mass index (HR 1.07,CI 1.01–1.13, p = 0.01), donor positive/recipient negative CMV status (HR 1.65,CI 1.03–2.6, p = 0.04), posttransplant weight gain (HR 4.7,CI 1.95–11.1, p < 0.001), pancreas rejection (HR 1.94.CI 1.3–2.9, p < 0.001) and 6 month fasting glucose (HR 1.01,CI 1.01–1.02, p < 0.001), hemoglobin A₁c, (HR 1.12,CI 1.05–1.22, p = 0.002) and triglyceride to high‐density lipoprotein (TG/HDL) ratio (HR 0.94,CI 0.91–0.96, p < 0.001). This study delineates the incidence and identifies risk factors for PTDM after PTX.     

The Temporal Changes of Trabecular Architecture in Ovariectomized Rats Assessed by MicroCT

To study the short- and long-term effects of estrogen deficiency on trabecular bone, three-dimensional measurements of proximal tibiae of ovariectomized rats were performed by micro-computed tomography (MicroCT). New three-dimensional (3D) techniques were employed to characterize the trabecular architecture from 0 to 110 days post-ovariectomy (OVX). These new methods no longer assume a plate or rod model of bone, but calculate trabecular thickness, separation, and number and their distribution by placing maximal spheres into the 3D representation of the structure. The model type of bone was quantified with the Structure Model Index (SMI). Utilizing these methods we found a rapid loss of trabecular bone in the first week after OVX. After the first week bone mass declined further, although the rate of loss was lower. In addition there was a complete change in model type from plate-like to rod-like within 7 days post-OVX, and then a very constant SMI after 12 days. After an initial thinning of trabecular structure, further bone loss seems to occur through removal of trabeculae, while the trabecular plate thickness remains constant. The heterogeneity of the network could be quantified by intra-individual standard deviation of local separations, which showed a stair-like progression, with a plateau between 12 and 60 days post-OVX. This study provides new insights into ovariectomy-related changes in cancellous bone structure evaluated by 3D MicroCT. In addition, these data suggest that the rapid change of model from plate-like to rod-like post-OVX may potentially introduce biases in the parameters that are determined using model-based algorithms, and these biases may modify the impact of age-related or therapeutic changes. Received: 19 December 2000 / Accepted: 16 April 2001     

Effects of Ethanol on in Vivo Cystometry and in Vitro Whole Bladder Contractility in the Rat

Purpose

It is known that acute ethanol intoxication can produce urinary retention in patients with benign prostatic hyperplasia. We evaluated the effects of ethanol on rat bladder function in vivo and in vitro.

Materials and Methods

Infusion cystometry was performed under urethane anesthesia with or without intravenous injection of ethanol. Voided volume, maximum voiding pressure, residual urine, bladder capacity, the pressure at which micturition was induced and voiding efficacy were compared. Subsequently, the in vitro whole bladder pressure generated by field stimulation, bethanechol, adenosine triphosphate and KCl in the presence of ethanol 0 to 5.0 percent was investigated.

Results

Intravenous administration of ethanol changed the in vivo cystometrogram. Bladder capacity and residual urine volume were significantly increased, and voiding pressure was decreased. Contractility of the isolated whole bladder to various kinds of stimulation in vitro was suppressed by ethanol in a dose-dependent manner. Washing the bladder and incubating it in normal Krebs' solution following exposure to 5 percent ethanol restored detrusor contractility.

Conclusion

Ethanol significantly impairs detrusor contractility in the rat in vivo and in vitro.     

胃旁路术对非肥胖型2型糖尿病大鼠糖代谢的影响

目的:观察胃旁路术对非肥胖型2型糖尿病大鼠(GK大鼠)糖代谢的影响.方法:GK大鼠20只,Wistar大鼠10只,随机分为GK手术组、GK假手术组和Wistar假手术组,每组10只;手术组行胃旁路术;测定术前1周及术后第1、2、4、8、12周各组体质量、空腹血糖(FPG)、糖化血红蛋白(HbA1c)水平和血清胰岛素(INS)含量.结果:术后12周,GK手术组大鼠体质量由术前的(255.10±21.09)g上升到(364.55±25.73)g,FPG和HbA1c分别由术前的(11.36±1.14)mmol/L和(8.91±0.36)%下降到(8.36±0.62)mmol/L和(6.35±0.46)%,而血清INS由术前(32.76±2.37)μIU/mL上升到(55.14±5.45)μIU/mL.结论:胃旁路术可以明显降低GK大鼠的空腹血糖,改善糖代谢障碍.     

糖尿病与勃起功能障碍病因研究进展

糖尿病 (DM)是勃起功能障碍 (ED)的危险因子之一。DM性ED病人阴茎组织出现以下病理变化 :平滑肌、内皮细胞退变 ,白膜增厚 ,血管及周围神经递质发生改变