SGK1在糖尿病小鼠肾脏皮质中时间差异性表达及意义

目的：研究血清和糖皮质激素诱导的蛋白激酶1（serum and glucocorticoid-inducible kinase 1,SGK1）在糖尿病（DM）小鼠肾脏皮质中时间上差异性表达及意义。方法: 采用链脲佐菌素（STZ）单次腹腔注射诱导小鼠糖尿病模型。将2月龄C57BL/6小鼠随机分成10组：第1、2、3、4、6、8、12周糖尿病小鼠组（DM₁、DM₂、DM₃、DM₄、DM₆、DM₈、DM₁₂）和相应的第1、4、8周正常对照组（N₁、N₄、N₈）。分别在DM模型制作成功后第1、2、3、4、6、8、12周末收集小鼠24 h尿量，检测24 h尿蛋白量；观察肾脏病理改变；半定量RT-PCR检测小鼠肾脏皮质SGK1及结缔组织生长因子（CTGF）mRNA的表达，Western blotting检测N₄、DM₄、DM₈组皮质SGK1、CTGF蛋白的表达。结果: 随着糖尿病病程的进展，DM组小鼠肾小球体积逐渐增大、系膜区逐渐增宽；DM组小鼠24h尿蛋白从第2周起开始逐渐增多，肾脏皮质SGK1 mRNA表达从第2周开始明显上调，在第４周达到峰值。CTGF随着糖尿病病程的进展表达逐渐递增。结论: SGK1在糖尿病早期肾脏表达峰值的出现及CTGF 持续递增的表达，提示SGK1在糖尿病肾病肾脏纤维化的发生发展过程中起重要作用。     

Alterations of glomerular matrix proteins in the pathogenesis of diabetic nephropathy

Summary Diabetic late complications are characterized by morphological and biochemical alterations of the extracellular matrix. In particular, longstanding diabetes causes quantitative and qualitative changes in basement membrane structure of retinal and renal capilleries. Immunohistochemical investigations of diabetic kidneys with diffuse glomerulosclerosis show increased collagen type IV deposition in the mesangial matrix and decreased heparan sulfate proteoglycan content in the mesangial matrix and glomerular basement membrane as well. In nodular glomerulosclerosis normal basement membrane components are decreased or absent while the occurrence of collagen type III in this stage has been interpreted as an irreversible alteration of the glomerular structure. These changes seem to be the underlying cause for the alterations in renal functions like persistent albuminuria and proteinuria. Increased intra- and extracellular levels of glucose and its derivatives are thought to be responsible for diabetic tissue dysfunction although there are reports on possible genetic defects causing increased susceptibility to develop diabetic nephropathy. Recent results, however, focuse on the role of glucose-induced cytokine secretion as mediator for altered metabolism of glomerular matrix proteins. In vitro studies with cultured kidney cells have shown that the glucose-induced dysregulation of the basement membrane synthesis may be mediated by a glucose dependent activation of protein kinase C. Alternatively or synergistically, the formation of AGE products formed after prolonged exposure of matrix proteins to elevated glucose may also lead to cytokine secretion subsequently inducing synthesis of extracellular matrix proteins. Studies in experimental animals confirm the diabetes induced dysregulation of the synthesis of extracellular matrix components on the molecular level.Abbreviations HSPG heparan sulfate proteoglycan - GBM glomerular basement membrane - ECM extracellular matrix - AGE advanced glucosylation end products - TNF tumor necrosis factor - bFGF basic fibroblast growth factor     

Eosinophilic pancreatitis in the newborn infant of a diabetic mother

Summary The authors have studied the pancreas of a premature female infant born to a diabetic mother. The findings included a peri-insular eosinophilic leucocyte infiltration, macropolinesia and a marked increase in B cells. In the exocrime parenchyma small B cells aggregates were also observed. B cells contained voluminous hypercromatic muclei and degranulated cytoplasm. Morphometric data demonstrated an increase in islet tissue. These morphological findings are indicative of excessive insulin secretion. The presence of eosinophilic leucocytes in pancreatic tissue and the pathogenic mechanism involved are discussed.     

Microangiopathy in human diabetic neuropathy

Summary Morphological change of endoneurial and perineurial vessels accompanied severe loss of myelinated axons in peripheral nerves of each of 17 patients with diabetic neuropathy. Vascular mural thickening averaged 18.9±9.9 m² in diabetic capillaries (n=11) vs. 6.9±4.1 m² in controls (n=7). Electron microscopy revealed vigorous endothelial proliferation as well as thickening and reduplication of basal lamina in each instance. Particular attention was paid to vessels which penetrate the perineurium en route to the endoneurial intertitium, since they provide a major portion of the endoneurial blood supply. Luminal narrowing and mural thickening of these vessels was compounded by basal laminar thickening of the perineurium. Fenestrated endoneurial capillary endothelium was noted in one case. Both demyelination and axonal degeneration were observed with intra-axonal glycogen accumulation in some axons. Morphometric analysis revealed extensive myelinated nerve fiber loss in diabetic nerves. These morphological findings emphasize the impact of diabetic microangiopathy on specialized endothelium and suggest that local anatomic factors in the perineurial sheath render the nerve vulnerable to chronic ischemia.Supported in part by the National Institute for Communicative Disorders and Stroke NS-14162 and by the Veterans Administration Research Service     

云南省2型糖尿病患者糖尿病肾病发病情况及危险因素分析

目的 了解云南省2型糖尿病（T2DM）患者糖尿病肾病（DN）发病情况及其危险因素,为防治DN提供科学依据。方法 采用随机整群抽样方法,以云南省社区T2DM患者（年龄≥18岁,且均在云南省居住≥1年）为调查对象,于2019年1—3月进行问卷调查、体格检查及实验室检测,统计DN发病情况。采用χ²检验及多因素非条件Logistic回归分析DN发病的影响因素。结果 共调查5 122例T2DM患者,男性2 317例（45.24%）,女性2 805例（54.76%）;平均年龄（56.28±19.03）岁,以45~59岁为主,共2 649例（51.72%）;婚姻状况以在婚为主,共3 834例（74.85%）;居住在城市2 190例（42.76%）,农村2 932例（57.24%）;文化程度以初中为主,共2 051例（40.04%）。DN发病1 462例,发病率为28.54%。多因素非条件Logistic回归分析结果发现,年龄60~90岁（OR=1.994,95%CI：1.409~2.821）、T2DM病程11~15年（OR=1.530,95%CI：1.207~1.939）、吸烟（OR=1.441,95%CI：1.203~1.726）、肉类摄入频次>1次/周（OR=1.347,95%CI：1.134~1.599）、肥胖（OR=1.678,95%CI：1.338~2.104）、高血压（OR=2.086,95%CI：1.367~3.182）、总胆固醇（TC）升高（OR=2.070,95%CI：1.842~2.327）及高密度脂蛋白胆固醇（HDL-C）降低（OR=1.799,95%CI：1.550~2.089）是云南省T2DM患者DN发病的危险因素,而参加体育锻炼（OR=0.613,95%CI：0.426~0.883）和糖化血红蛋白（HbA1c）达标（OR=0.573,95%CI：0.413~0.794）是T2DM患者DN发病的保护因素。结论 云南省T2DM患者DN发病率较高,年龄较大、T2DM病程较长、吸烟、肉类摄入频次、参加体育锻炼、高血压、HbA1c是否达标及BMI、TC、HDL-C是该地区T2DM患者DN发病的主要影响因素。     

糖尿病足患者发生多重耐药菌感染的危险因素研究

目的 探讨糖尿病足患者发生多重耐药菌（MDROs）感染的危险因素及病原菌分布情况。方法 以2019年1月至2020年12月青岛市某三甲医院内分泌门诊就诊的糖尿病足患者为研究对象进行资料收集、体格检查及空腹静脉血采集,并采用灭菌棉拭子擦拭创面拭取分泌物用于病原菌感染情况及耐药性检测。采用描述流行病学分析方法进行分析,并采用单、多因素分析方法对多重耐药影响因素进行分析。结果 本研究共对5 122例糖尿病足患者进行MDROs感染情况分析,年龄35~85岁,平均（61.03±11.19）岁,糖尿病病程1~29年,平均（12.32±7.16）年。多重感染者210例,多重感染率为4.10%。共分离出265株MDROs,居于前3位的MDROs分别是金黄色葡萄球菌109株（41.13%）、铜绿假单胞菌61株（23.02%）、大肠杆菌58株（21.89%）。主要的MDROs中金黄色葡萄球菌对苯唑西林、氨苄西林/舒巴坦、头孢唑林100%耐药,大肠杆菌对氨苄西林、哌拉西林/他唑巴坦、头孢他啶100%耐药,未见对万古霉素耐药菌。多因素Logistic回归分析结果显示,抗菌药物暴露史（OR=1.962）、因同一伤口住院次数>2次/年（OR=1.970）、骨髓炎（OR=4.323）、神经缺血性伤口（OR=1.269）和抗菌药物疗程≥5 d（OR=1.487、3.274、1.602）是糖尿病足患者发生MDROs感染的危险因素。结论 糖尿病足患者抗菌药物暴露史、因同一伤口住院次数>2次/年、骨髓炎、神经缺血性伤口以及使用抗菌药物疗程与发生MDROs感染存在密切关系。     

前列地尔辅助硫辛酸治疗糖尿病足溃疡合并感染的临床效果

目的探讨前列地尔辅助硫辛酸治疗糖尿病足溃疡合并感染对患者胰岛素样生长因子-1(IGF-1)、纤维连接蛋白(FN)、血管内皮生长因子(VEGF)水平及足背血流动力学的影响。方法选取2017年5月-2019年5月新疆医科大学第一附属医院收治的104例糖尿病足溃疡合并感染患者,采用随机数字表法将所选患者分为研究组(n=52)和对照组(n=52)。对照组给予硫辛酸进行治疗,研究组在此基础上给予前列地尔进行治疗,两组均治疗4周。比较两组治疗4周后的下肢静息疼痛改善情况,治疗前、治疗4周后的血清IGF-1、FN、VEGF水平及足背动脉血流速度和足背动脉内径,统计两组治疗期间的不良反应发生率。结果治疗4周后,研究组下肢静息疼痛总改善率为96.15%,高于对照组(P<0.05)。与治疗前比,治疗4周后,两组血清IGF-1、FN、VEGF水平及足背动脉血流速度、足背动脉内径均升高,且研究组均高于对照组(P<0.05)。治疗期间,研究组不良反应发生率为5.77%,低于对照组(P<0.05)。结论前列地尔辅助硫辛酸治疗糖尿病足溃疡合并感染,可显著提高患者血清IGF-1、FN、VEGF水平,改善其足背血流动力学,并能缓解患者下肢静息疼痛,降低不良反应发生率。     

老年Ⅱ型糖尿病患者血清NO水平与肾功能变化的相关性研究

目的探讨一氧化氮(NO)在老年Ⅱ型糖尿病肾病发病过程中的变化规律及其与肾功能的关系。方法采用Griess法检测48例Ⅱ型DM病人血清NO值在水平及与肾功能有关的指标,并与17例正常人进行比较,结果血清NO值在正常尿蛋白(DMI)组(88.86±9.61umol/l)和微量尿蛋白(DMII)组(90.00±17.94umol/l)明显高于对照组(56.70±9.53umol/l)(P＜0.01),至临床肾病期血浆NO浓度明显降低(63.25±8.64umol/l)(P＞0.05);NO与BUN、BCR呈负相关,而与CCR呈正相关。结论血清NO水平的动态变化与Ⅱ型DM肾病的发生、发展有密切联系。     

局部药物注射与口服药治疗三叉神经痛的疗效对比

目的：观察局部注射药物与口服药治疗三叉神经痛的疗效差异。方法：选择门诊三叉神经痛的患者,并随机分成两组,即口服药物组给予卡马西平100mg1-2次/天,若不能止痛每天增加100mg ,直到控制疼痛为止,将最小有剂量作为维持量,一般为600-800mg/d,共36例。局部药物注射组以4%氢羟强的松龙0.5ml加2%利多卡因1.5ml混合后准确地注射到罹患神经通过的骨孔处,共32例。结果：口服药物组6个月有效27例,有效率75%,局部药物注射组6个月有效30例,有效率94%。结论：局部药物注射组的疗效明显优于口服药物组。     

锌对糖尿病大鼠血脂及脂质过氧化作用的影响

目的：观察锌对四氧嘧啶诱导的糖尿病大鼠脂质代谢及抗氧化系统的影响。方法：健康雄性Wistar大鼠32只,随机分成3组：正常对照组、糖尿病对照组、补锌组。补偿组每日以10mg/kgbw的Zn灌胃,60d以后,取血测血糖、胰岛素、血氧化指标等。结果：补锌组大鼠血糖较实验前明显降低;TC、TG水平明显低于阳性对照组;红细胞SOD、全血GSH－Px活力明显提高,MDA含量明显下降。结论：锌可以有效地缓解糖尿病大鼠的高血糖症状、纠正其血脂代谢紊乱、提高其抗氧化能力。