糖尿病大鼠视网膜基因表达谱差异的初步分析

目的 建立大鼠正常视网膜和糖尿病8周视网膜基因表达谱，比较两者差异，初步分析糖尿病视网膜病变的相关基因。方法 通过限制片段差异显示 PCR（ restriction fragments differential display-PCR，RFDD-PCR）获得正常大鼠视网膜及8周糖尿病大鼠视网膜组织转录组片段。应用Fraent Analysis等软件，对差异片段进行生物信息学分析，初步确定糖尿病视网膜病变相关基因／表达序列标签（ expression sequence tag, Ksr）。结果 获得有意义的片段共3639个，有差异的片段840个，占表达数的23．08％。其中包括5个视觉传导相关基因，13个兴奋性神经递质受体基因和3个抑制性神经递质受体基因。糖尿病8周大鼠视网膜Rhodopsin kinase,β-arrestin,Phosducin, rod photoreceptor cGMP-gated channel 和 Rpe65的表达下调，离子型谷氨酸受体iGluR1-4下调，代谢性谷氨酸受体及γ-氨基丁酸受体各亚型则普遍上调，而甘氨酸受体表达无变化。结论 糖尿病8周大鼠神经视网膜已受到累及，其基因表达模式的改变，可能与糖尿病早期视功能损害有关。     

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     

Action du clopamide et de l'acide ethacrynique sur la sécrétion de rénine chez le chien

Summary Renin secretion was studied in anesthetized dogs (Pentobarbital), after an injection of 5 mg/kg i.v. clopamide (10 animals) or ethacrynic acid (10 animals). Renin activity in venous renal blood (Boucher's method), renal blood flow (electromagnetic flowmeter), blood pressure, diuresis and natriuresis have been measured simultaneously. Basic renin secretion was 22,4±8,2 ng/g of kidney/min. During the 8 min following the ethacrynic acid injection renin secretion increased to 74,4±41,1 ng/g of kidney/min (p<0.005). Within the same time it dropped to 11.1±6.8 ng/g of kidney/min (p<0.005) after clopamide.These variations of renin secretion are related to the diuretic's action on the nephron, and depend on an endorenal mechanism. Ethacrynic acid suppresses the corticopapillary gradient while clopamide does not. We have not found any correlation between renin secretion and either natriuresis (mg/min) or diuresis (ml/min). But there is a connection (r=0.7367) between renin secretion after ethacrynic acid injection and sodium concentration in urine.

     

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.     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

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     

中药治疗糖尿病微血管病变的研究进展

糖尿病及其并发症病是全世界关注的重大公共卫生问题。糖尿病微血管病变是糖尿病虚损夹血瘀形成的血管并发症,以微循环障碍并伴有透明样物质沉积为基本病理改变特征,糖尿病肾病、糖尿病视网膜病变和糖尿病神经病变最为常见。糖尿病微血管病变可追溯到糖尿病前期,随着糖尿病发生发展动态演进不断加重,需及早干预。临床在降糖、降脂、降压的基础治疗上,多选择抗氧化应激、抗炎、改善微循环和抗血管新生的药物治疗糖尿病微血管并发症。糖尿病微血管病变属于中医“络病”的概念,中药治疗糖尿病微血管病变的核心是在降糖的基础上保护“孙络-微血管”,组方多为补气滋阴、清热活血药味配伍而成。该文基于糖尿病微血管病变的中西医认识及治疗原则,简要概述针对不同证型治疗糖尿病微血管病变的常用方剂,如白虎加人参汤、玉液汤、四妙勇安汤、葛根芩连汤、六味地黄丸及一些现代制剂,同时概述方剂常用药味,如人参、黄芪、地黄、枸杞子、三七、丹参、金银花、葛根的研究进展,以期为中药治疗糖尿病微血管病变提供临床依据和理论指导。     

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。