改良构建大鼠单侧输尿管梗阻肾间质纤维化模型

文题释义：肾盂积液：输尿管完全或不完全梗阻时,由于尿液无法正常排出体外而导致肾盂积液。慢性肾盂积液引起的肾脏损伤是不可逆的,可由多种上尿路梗阻性疾病诱发,导致肾盂肾盏扩大,肾小管与肾小球结构与功能丧失,进而肾组织萎缩。 肾间质纤维化：是各种慢性肾病发展至终末期的共同病理特征,以肾小管间质瘢痕硬化为特征,最终导致肾脏组织功能完全丧失。该过程受到转化生长因子β、成纤维细胞生长因子、内分泌等信号通路的调控,肾间质纤维化动物模型是研究相关药物药理机制的重要模型。 背景：传统的大鼠单侧输尿管梗阻手术方法,可以在较短的时间内(一两周)导致动物梗阻侧肾脏发生肾间质纤维化,但具有术后并发症较多、死亡率较高的缺点。 目的：优化并改良大鼠单侧输尿管梗阻手术操作,降低动物术后的并发症发生率,提高存活率,检测改良单侧输尿管梗阻方法建模大鼠的病理生理指标,为功能药理学基础研究提供背景数据支持。 方法：①取20只雄性SD大鼠,随机分为4组,分别进行传统单侧输尿管梗阻方法结扎、改良单侧输尿管梗阻方法结扎、不游离输尿管结扎、开腹腔但不结扎输尿管(假手术组)操作,术后14 d时比较组间大鼠肾间质纤维化成模率、死亡率、术后并发症发生率的差异;②另取28只SD大鼠,雌雄各半,随机分为改良组与假手术组,采用尿液分析、血细胞分析、血液生化分析方法,检测两组大鼠的生理指标,并通过苏木精-伊红染色与Masson染色法,观察改良组大鼠术后14,21 d时的肾脏组织病理学结果。 结果与结论：①与不游离输尿管结扎组大鼠相比,传统单侧输尿管梗阻组和改良单侧输尿管梗阻组大鼠的成模率高;②在单侧输尿管梗阻手术操作过程中,采用输尿管中段双结扎、中间不剪断的改良方法与传统方法相比,操作更简便易行,手术开创更小,肾间质纤维化成模快、成模率较高,动物术后死亡率与并发症发生率均低;③改良组与假手术组相比,术后14 d时的尿素氮、谷草转氨酶、白蛋白等血液生化指标差异有显著性意义(P < 0.05),其梗阻侧肾脏的组织病理切片苏木精-伊红染色与Masson染色结果均可见典型的肾间质纤维化病理特征。 ORCID: 0000-0001-7823-2897(孙杰) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Effects of a 12-wk whole-body vibration based intervention to improve type 2 diabetes

Objective

To test the feasibility, safety and effectiveness of a 12-wk whole body vibration (WBV) intervention on glycemic control, lipid-related cardiovascular risk factors and functional capacity among type 2 diabetes mellitus (T2DM) patients in a primary care context.

Methods

Fifty non-insulin dependent T2DM patients were randomized 1:1 to an intervention group that, in addition to standard care, received a 12-wk WBV intervention, and a control group receiving only standard care (from February 2012 through May 2012). Outcomes, including glycated hemoglobin (HbA1c), fasting blood glucose, lipid-related cardiovascular risk factors (i.e., cholesterol, triglycerides, lipoproteins, LDL/HDL and atherogenic index) and functional capacity were measured at baseline and after the 12-wk intervention.

Results

After intervention, there was a reduction in HbA1c and fasting blood glucose when compared to the control group, with a mean difference in change scores between groups of −0.55% (95% CI −0.15 to −0.76) and −33.95 mm/dl (95% CI −51.38 to −3.47), respectively. Similarly, most lipid-related cardiovascular risk factors (i.e., cholesterol, triglycerides and atherogenic index) were also reduced (p < 0.05).

Conclusion

A 12-wk WBV intervention in a primary care context is feasible, safe and effective in improving glycemic profile, lipid-related cardiovascular risk factors and functional capacity among T2DM patients.

Trial number

ACTRN12613000021774.     

血清糖化白蛋白水平升高对糖尿病视网膜病变的诊断价值

目的:分析血清糖化白蛋白(GA)水平升高对2型糖尿病(T2DM)视网膜病变(DR)患者的诊断效能。方法:T2DM患者120例,依据是否合并DR将其分为DR组(50例)和非DR组,即T2DM组(70例)。液态酶法测定血清GA,液相色谱法测定全血HbA1c,比较两组GA和HbA1c水平差异及其对DR诊断的敏感度、特异度、阳性似然比和阴阳性预测值,分析GA和HbA1c与DR危险性的关系。结果:DR组GA、HbA1c水平(25.11±6.50%和9.38±1.77%)较T2DM组(21.21±4.50%和8.71±1.31%)明显升高(P0.05)。GA和HbA1cROC曲线下面积最大值分别为0.68和0.61,对应的诊断DR的cut off值分别为24.00%和9.35%,GA诊断DR灵敏度为62.00%,高于HbA1c的38.00%(P0.05),GA诊断DR的特异度、阴阳性预测值略优于HbA1c,但差异无统计学意义(P0.05)。GA诊断DR的阳性似然比为2.71,优于HbA1c的1.48。Logistic回归分析,GA回归系数的Waldχ2值为7.488(P0.05),其致DR的危险因子(OR)为1.16;HbA1c的Waldχ2为0.226(P0.05)。结论:DR患者GA水平明显高于非DR患者,是DR的危险因素;GA24.00%可作为DR的诊断指征。     

Notch信号通路蛋白在糖尿病肾病患者肾组织中的表达及意义

目的观察糖尿病肾病肾组织中Notch信号通路的表达情况,探讨其与糖尿病肾病肾脏损害的关系。方法收集10例手术切除的远离肿瘤的瘤旁肾组织及34例糖尿病肾病肾穿刺组织,免疫组化检测Jagged1、Notch1、NICD1和Hes1蛋白表达情况。结果 Jagged1、Notch1、NICD1和Hes1蛋白在糖尿病肾病肾组织中高表达,并与24小时尿蛋白成正相关,而与肾小球滤过率成负相关。结论 Notch信号通路在糖尿病肾病肾组织中激活,与糖尿病肾病肾脏损伤有关。     

干性与湿性愈合疗法在糖尿病足坏疽治疗中的应用

糖尿病足坏疽可分为干性坏疽、湿性坏疽、混合性坏疽。在同一伤口的不同时期,可分别采用干性或湿性愈合疗法,其辨证的关键在于局部血运及感染的情况。干性坏疽初期使用干性愈合疗法,加速坏死组织的脱水,待局部血运改善后采用湿性愈合疗法,促进创面愈合。湿性坏疽初期首先应用干性愈合疗法,控制感染,待感染控制后可采用湿性愈合疗法。混合性坏疽二者可同时应用。干性愈合疗法是控制感染的手段之一,湿性愈合疗法是去腐生肌、偎脓长肉的过程,二者相辅相成,相互转变,把握好应用时机,是促进慢性创面愈合的关键。     

Requirement for TLR2 in the development of albuminuria,inflammation and fibrosis in experimental diabetic nephropathy

Inflammation and fibrosis are essential elements of diabetic nephropathy (DN). We tested the hypothesis that these elements are dependent upon Toll-like receptor 2 (TLR2) signalling by examining WT and TLR2^-/- mice in an experimental model of DN. Diabetes was induced in WT and TLR2^-/- mice by i.p. injection of streptozotocin. Kidney injury was assessed at 6, 12 and 24 weeks after induction of diabetes. Gene expression of TLR2, its endogenous ligands and downstream cytokines, chemokines and fibrogenic molecules were upregulated in kidneys from WT mice with streptozotocin diabetes. TLR2^-/- mice were protected against the development of DN, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic WT controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA) and expression of fibrogenic genes (TGF-β and fibronectin) were also evident in TLR2 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR2 activation in podocytes and tubular epithelial cells (TECs) in vitro, resulting in NF-κB activation, inflammation and TGF-β production. We conclude that TLR2 was required for the full development of inflammation, kidney damage and fibrosis in this model of DN. As TLR2 is known to be expressed by intrinsic kidney cells and as high concentration glucose stimulated podocytes and TECs in vitro to express TLR2 and TLR2 ligands, pro-inflammatory and pro-fibrotic cytokines in a TLR2 dependent manner in the present study, it appears likely that TLR2 signalling in intrinsic kidney cells contributes to the pathogenesis of diabetic nephropathy.     

Lycopene ameliorates renal function in rats with streptozotocin-induced diabetes

Aim: To study the effect of lycopene on ameliorating renal function of diabetic nephropathy. Methods: Sixty male SD rats were divided into four groups: normal untreated (NC-U), normal treatment (NC-L), diabetes untreated (DM-U) and diabetes treatment (DM-L). DM was prepared by a single injection of STZ (70 mg/kg, intraperitoneally) dissolved in 0.1 M citrate buffer (pH 4.5). DM-U and NC-U rats received control diet; DM-L and NC-L rats received lycopene. After treated with lycopene for 8 weeks, blood was obtained for analyzing plasma lipid profiles, glucose and renal function. The kidneys were used to determine SOD activity, malondialdehyde (MDA) level, processed for histological examination and western blot. Results: Treatment of diabetic rats with lycopene decreased the values of blood urea nitrogen, 24 h urea protein and creatinine. The serum lipids like TC, TG, and LDL were decreased and HDL was increased in DM-L rats when compared with those of diabetic rats. Administration of lycopene decreased the levels of MDA content and expression of CTGF, increased Akt/PKB phosphorylation and SOD activity in diabetic renal tissues. Conclusions: Lycopene protects against development of diabetic nephropathy and ameliorates renal function via improving oxidative status and regulating p-Akt and CTGF.     

应用FibroTouch技术评价2型糖尿病肾病患者肝脏脂肪变性和纤维化程度及二者相关性

目的 利用FibroTouch技术,评价2型糖尿病肾病（DN）患者肝脏脂肪变性和肝脏纤维化的程度及二者的相关性。方法 选取2型糖尿病肾病患者90例。根据肾小球滤过率（eGFR）将其分为三组,eGFR≥90ml?min-1(1.73m2)-1为A组(30例),60ml?min-1?(1.73m2)-1≤eGFR＜90ml?min-1?(1.73m2)-1为B组（30例）,eGFR＜60 ml?min-1?(1.73m2)-1为C组（30例）,同时选取30名健康志愿者为对照组。应用FibroTouch技术获得肝脏脂肪衰减值（db/m）和肝脏硬度值（Kpa）。结果 各组肝脏脂肪衰减值和肝脏硬度值比较,A、B、C组均明显高于对照组（P均＜0.05）,B、C组均高于A组（P均＜0.05）,C组高于B组（P＜0.05）;肝脏脂肪衰减值和肝脏硬度值呈正相关关系（r=0.733,P＜0.01）。结论 应用FibroTouch技术可以准确、无创地评价DN患者的肝脏脂肪变性和纤维化程度,具有重要的临床意义。     

Is lactic acidosis predictive of outcomes in pediatric diabetic ketoacidosis?

ObjectivesThe objective of this study was to investigate the significance and prevalence of lactic acidosis in pediatric diabetic ketoacidosis (DKA) presenting to the emergency department.MethodsA retrospective cohort study of children (age ≤ 21 years) presenting to a tertiary care emergency department in DKA from December 1, 2015 to December 1, 2018. Patients needed to have DKA requiring admission to the pediatric intensive care unit and have had a lactate level collected while in the emergency department to be included.Results92 patients resulting in 113 encounters had DKA and a lactate level collected in the emergency department. The mean lactate level was 3.5 mmol/L (±SD 2.1). 72 (63.7%) encounters had lactic acidosis (p < 0.001). There was no significant association between the presence of lactic acidosis and pediatric intensive care unit length of stay (p = 0.321), hospital length of stay (p = 0.426), morbidity (p = 0.552) and mortality (p = 1.000). Initial glucose levels were significantly higher in the patients presenting with lactic acidosis (p = 0.001).ConclusionsLactic acidosis is a common finding in pediatric DKA patients presenting to the emergency department. Serum lactate alone should not be used as an outcome predictor in pediatric DKA.