血管内皮祖细胞与糖尿病微血管病变研究进展

糖尿病微血管病变严重影响了患者生活质量,是患者致死致残主要原因。微血管病变主要表现在视网膜、肾、神经、心肌组织。微血管病变的机制尚未完全清楚,近年越来越多研究发现血管内皮祖细胞(endothelial progenitor cells,EPCs)是该病发病重要原因。EPCs有分化为成熟的内皮细胞并且参与新血管形成和新生的能力。正常情况下内皮损失和EPCs对内皮的修复作用处于动态平衡状态,一旦EPCs受损,内皮损害和修复之间的平衡被打破,内皮层的完整性遭到破坏,必然参与糖尿病血管病变的发生发展。国内外大量研究证明糖尿病合并大血管病变EPCs数目功能改变,而糖尿病合并微血管病变EPCs的怎样变化?本文就EPCs与糖尿病微血管病变的关系进行系统综述。     

海拔高度对2型糖尿病患者循环内皮祖细胞及低氧诱导因子的影响*

目的: 探讨不同海拔地区2型糖尿病患者循环内皮祖细胞数量及相关检测指标的变化情况,为2型糖尿病血管并发症的研究和治疗提供依据。方法: 选取386 m低海拔地区(咸阳市)和1 520 m高海拔地区(兰州市)各一家医院内被诊断的2型糖尿病患者(25人/29人)和健康体检者(20人/20人)。用全自动生化分析仪检测两组人群的血脂、血糖和糖化血红蛋白指标,用酶联免疫吸附试验(ELISA)检测低氧诱导因子-1α(HIF-1α)的浓度,用流式细胞仪测定外周血循环内皮祖细胞(EPCs)的数量。结果: 无论在低海拔还是高海拔地区,糖尿病组较健康组循环EPCs数量降低(P＜0.01),体质指数(BMI)、腰臀比(WHR)、甘油三酯(TG)、空腹血糖(FBG)及糖化血红蛋白含量(HbAlc)增高(P＜0.05);与低海拔组相比,无论高海拔的糖尿病患者还是健康者,HIF-1α的表达水平均明显增加(P＜0.05),而循环EPCs数量明显降低(P＜0.05),且有循环EPCs数量健康者高于2型糖尿病无血管并发症者高于2型糖尿病伴血管并发症者的表现(P＜0.05)。结论: 海拔高度增加,2型糖尿病(T2DM)患者体内HIF-1α表达水平增加,循环EPCs数量降低,且与其血管病变程度密切相关。因此有望通过对高海拔地区T2DM患者进行EPCs的移植来实现对糖尿病血管并发症的预防和改善。     

2型糖尿病患者血糖波动与糖尿病视网膜病变的相关性分析

目的:探讨2型糖尿病(T2DM)患者血糖波动与糖尿病视网膜病变(DR)的关系.方法:T2DM患者进行眼底照相或眼底荧光造影,根据DR程度分为糖尿病背景期视网膜病变(BDR)组、糖尿病增殖期视网膜病变(PDR)组、无视网膜病变(NDR)组,记录年龄、性别、体重指数、病程、测量血压、糖化血红蛋白、空腹胰岛素、餐后2h胰岛素、空腹C-肽、餐后2hC-肽、血脂指标.选取三组中上述基线指标具有可比性的病例共106例(BDR组38例,PDR组35例,NDR组33例)纳入观察.采用动态血糖监测系统(CGMS)连续监测患者血糖72 h.结果:各组间平均血糖水平(MBG)、血糖标准差(SDBG)、平均血糖波动幅度(MAGE)及血糖波动最大幅度(LAGE)相比较有统计学差异(P＜0.05).Spearman相关分析显示,糖尿病视网膜病变(DR)与MBG、SDBG、MAGE及LAGE呈正相关(P＜0.05).校正MBG后,糖尿病视网膜病变(DR)与SDBG、MAGE及LAGE的相关系数分别为0.297、0.396、0.284(P＜0.01).结论:血糖波动与糖尿病视网膜病变(DR)的发生发展有关,应尽早干预.     

PR间期在糖尿病视网膜病变早期诊断中的价值

目的:探讨PR间期在糖尿病视网膜病变早期诊断中的价值。方法:选取2型糖尿病(T2DM)患者578例,依据眼底照相结果,将研究对象分为无视网膜病变(NDR)组345例、单纯型视网膜病变组(BDR)组191例、增殖型视网膜病变组(PDR)组42例。比较各组一般资料及PR间期长度,进行统计分析。结果:所有患者的PR间期均值为162.76±20.10 ms。PDR组和BDR组患者PR间期的平均长度显著高于NDR组(P0.001)。Logistic回归分析结果显示PR间期每延长1 ms,T2DM患者患得DR的风险增加2.7%倍(OR=1.027,95%CI:1.016~1.038,P0.001);PR163 ms是PR≤163 ms的T2DM患者患得DR风险的2.727倍(OR=2.72795%CI:1.936~3.842,P0.001)。结论:心电图PR间期与糖尿病视网膜病变有显著的相关性,可以作为一个简单、无创的辅助检查用于早期筛查糖尿病视网膜病变。     

eNOS/NO途径在单侧输尿管梗阻小鼠肾间质微血管病变中的作用与机制

目的探讨内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)和一氧化氮(nitric oxide,NO)在单侧输尿管梗阻(unilateral ureteral obstruction,UUO)肾间质纤维化小鼠微血管病变中的作用及机制。方法64只KM小鼠随机分为两组:假手术组n=32只;单侧输尿管梗阻UUO组n=32只。观察4周,每周检测各组小鼠血BUN、Scr及一氧化氮,流式细胞计数外周血CD133+/VEGFR+内皮祖细胞(endothelial progenitor cells,EPCs)、Masson染色观察肾组织形态学变化,免疫组化法检测肾间质CD34+表达计数微血管密度,实时定量PCR检测肾皮质e NOS、VEGF mRNA表达。结果 UUO组血一氧化氮、内皮祖细胞计数、肾间质微血管密度、e NOS、VEGF mRNA表达水平持续下降,在第2、3、4周与对照组差异有统计学意义。一氧化氮水平与肾间质微血管密度呈正相关(r=0.715,P0.05);e NOS mRNA表达水平与肾间质微血管密度(r=0.624,P0.05)、内皮祖细胞计数(r=0.375,P0.05)、VEGF mRNA(r=0.351,P0.05)呈正相关。结论 e NOS/NO途径参与了UUO小鼠肾间质微血管的调节,其调节涉及对血管舒张功能影响、介导促血管肾脏因子VEGF mRNA表达及动员内皮祖细胞等机制。     

电针介导eNOS动员内源性EPCs促MCAO/R大鼠脑内血管再生

目的探讨内皮型一氧化氮合酶(e NOS)在电针干预下对局灶脑缺血/再灌注大鼠骨髓及外周血中内皮祖细胞(EPCs)数量变化的影响,及其促大鼠脑内血管再生的机制。方法线栓法制备大鼠局灶脑缺血/再灌注模型,针刺"百会"穴及左侧"四关"穴。100只SD雄性大鼠随机分为正常组(N组)、模型组(I/R组)、模型+电针组(I/RE组)、模型+电针+L-NAME组(I/REL组)。除N组外的各组局灶脑缺血1.5 h后分为再灌注1、2、7 d三个亚组,每个亚组10只大鼠。在各时间点采用流式细胞术检测外周血及骨髓中VEGFR2+EPCs数量,荧光定量PCR技术检测缺血皮质区VEGFR2 mRNA的表达,免疫组织化学法检测缺血皮质区VEGFR2阳性细胞表达及CD34标记的微血管计数。结果与I/R组比较,电针可明显提高骨髓及外周血中EPCs的数量(P0.01,P0.05),而I/REL组的VEGFR2+EPCs数量相比于I/RE组则显著降低(P0.01)。各时间点I/RE组缺血皮质区VEGFR2阳性细胞表达,VEGFR2 mRNA表达及CD34微血管计数明显高于I/R组(P0.01),而I/REL组与之比较则显著减少(P0.01)。结论电针可动员局灶脑缺血/再灌注大鼠内源性EPCs促大鼠缺血脑区血管再生,该作用在e NOS被抑制后减弱,推测电针动员EPCs促血管再生的作用与e NOS的激活有关。     

2型糖尿病性视网膜病变临床因素分析

目的:探讨影响2型糖尿病视网膜病变(DR)发病的相关临床因素。方法:回顾性分析483例2型糖尿病患者的临床资料。结果:2型糖尿痛DR患病率为35%(169/483),其中非增殖型视网膜病变(NPDR)73.4%(124/169),增殖型视网膜病变(PDR)26.6% (45/169)。DR患者的病程、SBP、合并肾脏病变、合并心脏病变、HbA1c、TC、TG、LDL-c、BUN和Cr均显著高于NDR患者(P<0.05);Logistic回归分析显示病程、年龄、SBP、TC、LDL-c、合并心脏病变和/或肾脏病变是DR发病的危险因素。结论:DM病程、患病年龄、SBP、HbA1c、TC、LDL-c、合并心脏病变和/或肾脏病变、肾功能是DR发生发展的危险因素。     

2型糖尿病患者微血管病变与血清代谢学指标的关系

目的:探讨2型糖尿病(T2DM)患者微血管病变与血清代谢学指标的关系。方法:选择我院于2015年7月~2016年7月间收治的T2DM患者共96例,按是否存在微血管病变分为观察组(n=43,存在微血管病变)及对照组(n=53,无微血管病变)。检测并对比两组患者血清中三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、空腹血糖(FBG)、糖化血红蛋白(HbA1C)、同型半胱氨酸(Hcy)、血清胱抑素C(CysC)及血管内皮生长因子(VEGF)水平,并采用logistic回归分析T2DM微血管病变的危险因素。结果:观察组病程、吸烟率高于对照组,差异有统计学意义(P0.05);观察组TG、LDL、HbA1C、CysC、Hcy、VEGF水平均高于对照组,差异均有统计学意义(P0.05);两组TC、HDL水平比较,差异无统计学意义(P0.05);经logistic回归分析显示,病程、CysC、Hcy、VEGF为微血管病变的危险因素(OR=1.975,3.643,4.054,4.214,P0.05)。结论:CysC、Hcy、VEGF为微血管病变的危险因素,对其水平的检测有助于早期T2DM微血管病变诊断及治疗。     

血清TNF-α与糖尿病微血管病变的关系

目的:研究肿瘤坏死因子α(tumor necrosis factor-alpha;TNF-α)与糖尿病微血管病变的关系.方法:将67例糖尿病患者,通过是否合并微血管痛变,分成无微血管病变组(DMI组)32例,合并微血管病变组(DM2组)35例,设正常时照组25例对比,用放射免疫法测得血清TNF-α,三组间进行比较.测受检者总胆固醇、甘油三酯、空腹血糖、糖化血红蛋白等指标,三组间比较.结果:2型糖尿病患者肿瘤坏死因子-α水平显著高于正常对照组(P＜0.01),糖尿病合并微血管病变组较糖尿病无微血管病变组其表达也明显升高(P＜0.01).结论:TNF-α表达的上调可能与糖尿病微血管病变的发生、发展关系密切     

脑心清片对缺血性心脏病患者外周血中内皮祖细胞功能的影响

目的:观察脑心清片对缺血性心脏病(ischemic heart disease,IHD)患者外周血中内皮祖细胞(endothelial progenitor cells,EPCs)数量及功能的变化。方法:将40例IHD患者随机分为脑心清组30例和贝那普利组10例;用密度梯度离心法从外周血中分离单核细胞;分别观察治疗前后EPCs的粘附能力、迁移能力和体外生成血管能力。结果:脑心清组在治疗后IHD患者外周血中EPCs数量显著升高,其粘附能力、迁移能力和体外生成血管能力也明显改善。结论:脑心清片可以升高IHD患者外周血中EPCs数量并改善其功能。     

Brain Insulin-Like Growth Factor-II mRNA Content Is Reduced in Insulin-Dependent and Non-Insulin-Dependent Diabetes Mellitus

Abstract: Diabetic encephalopathy, characterized by structural, electrophysiological, neurochemical, and cognitive abnormalities, is observed in insulin-dependent diabetes mellitus (IDDM) and non-IDDM (NIDDM). Identification of early biochemical lesions potentially may provide clues pointing to its pathogenesis. Insulin-like growth factors (IGFs) are neurotrophic factors that recently have been implicated in the pathogenesis of diabetic neuropathy. Because IGF-II is the predominant IGF in adult brain, we tested the hypothesis that IGF-II gene expression is decreased in the CNS in both IDDM and NIDDM. Brain and spinal cord were isolated from streptozotocin-diabetic rats, a model of IDDM with weight loss and impaired insulin production. IGF-II mRNA content was measured by northern and slot blots. After 2 weeks of diabetes, IGF-II mRNA content per milligram of tissue wet weight, as well as per unit of poly(A)⁺ RNA, declined significantly (p≤ 0.05) in brain and spinal cord. Insulin replacement therapy partially restored IGF-II mRNA levels in brain, cortex, medulla, and spinal cord. The obese, hyperinsulinemic, and spontaneously diabetic (fa/fa) Zucker rat was used as a model of NIDDM. Brain weight (p < 0.025) and IGF-II mRNA contents (p < 0.01) were significantly decreased in (fa/fa) versus lean nondiabetic (+/?) rats. Therefore, the decline in IGF-II mRNA levels in diabetic brain was independent of the type of diabetes, the direction of change in body weight, and the insulinemic state. We speculate that this early biochemical lesion may contribute to the development of diabetic encephalopathy.     

Diabetic retinopathy in the Eastern Morocco: Different stage frequencies and associated risk factors

Diabetes is a major cause of morbidity and mortality worldwide. It can affect many organs and, over time, leads to serious complications. Diabetic retinopathy (DR), a specific ocular complication of diabetes, remains the leading cause of vision loss and vision impairment in adults. This work is the first in Eastern Morocco aimed at identifying the different stages of DR and to determine their frequencies and associated risk factors. It is a case-control study conducted from December 2018 to July 2019 at the ophthalmology department of Al-Irfane Clinic (Oujda). Data were obtained from a specific questionnaire involving 244 diabetic patients (122 cases with retinopathy vs 122 controls without retinopathy). All results were analyzed by the EPI-Info software. This study shows a predominance of proliferative diabetic retinopathy (PDR) with 57.4% of cases (uncomplicated proliferative diabetic retinopathy (UPDR): 23.8%; complicated proliferative diabetic retinopathy (CPDR): 33.6%). The non-proliferative diabetic retinopathy (NPDR) represents 42.6% (minimal NPDR: 8.2%; moderate NPDR: 26.2%; severe NPDR: 8.2%). The determinants of DR were insulin therapy, high blood pressure, poor glycemic control and duration of diabetes. Regarding the chronological evolution, retinopathy precedes nephropathy. Diabetic nephropathy (DN) was present in 10.6% of cases especially in patients with PDR. In summary, the frequency of PDR was higher than that of NPDR. DR appears before DN with a high frequency of DN in patients with PDR. Good glycemic control and blood pressure control, as well as early diagnosis are the major preventive measures against DR.     

Unidades de pie diabético en España: conociendo la realidad mediante el uso de un cuestionario

ObjectiveTo ascertain the number of diabetic foot units (DFUs) in Spain, the specialists working in them, and the population covered by them.Material and methodsThe Spanish Group on the Diabetic Foot (SGDF) prepared and agreed a questionnaire based on the recommendations of the 2011 International Consensus on the Diabetic Foot (ICDF). From October to December 2012, the questionnaire was sent to members of three scientific societies formed by professionals involved in the care of patients with diabetes mellitus. Population coverage of the responding centers and DFUs was estimated using the 2012 population census.ResultsSeventy five questionnaires were received, 64 of them from general hospitals, which accounted for 13% of the general hospitals of the National Health System. It was calculated that they provided coverage to 43% of the population. Thirty four centers answered that they had a DFU. Specialized diabetic foot care was only provided to 25% of the population. The number of different professionals working at diabetic foot units was 6.3 ± 2.7. Classification of DFUs based on their complexity was as follows: 5 basic units (14.7%), 20 intermediate units (58.8%), and 9 excellence units (26.5%).ConclusionsThe number of DFUs reported in this study in Spain is low, and allow for foot care of only one out of every four patients with diabetes. Spanish health system needs to improve diabetic foot care by creating new DFUs and improving the existing ones.     

糖尿病性白内障相关的酶及蛋白质

在我国白内障是造成视力障碍的主要因素。糖尿病性白内障(DC)是糖尿病的慢性并发症之一,其致盲率仅次于糖尿病视网膜病变(DR),糖尿病的发病率逐年上升的同时,DC的发病率也在增加。虽然白内障手术能够治愈DC,但研究人员仍致力于研究其发病机制以求通过药物途径治疗或预防DC。最近的研究显示,白内障的生成与晶状体内某些成分的改变有直接或间接的关系,DC发病过程中更是有一些特殊的改变:多元醇通路与DC的发展有着紧密的联系,有学者认为多元醇积聚诱发了白内障形成;氧化损伤在白内障形成过程中起了重要作用,而高血糖使得晶状体中多种抗氧化酶受损;晶状体本身是人体蛋白质含量最高的器官,白内障本质上即为结构蛋白的变性,而某些晶状体蛋白作为结构蛋白的同时又具有功能性蛋白的特性,其性质的改变引发晶状体混浊。本文针对DC相关的某些晶状体蛋白及酶类的研究进展做一综述。     

VIPergic innervation of diabetic pancreas in rats

Morphological, ultrastructural, and immunocytochemical studies of nerves containing vasoactive intestinal peptide (VIP) are described in diabetic pancreas of rats after streptozotocin treatment. The observations covered 48 hours and 6 months following streptozotocin treatment. At the ultrastructural level, degenerative changes were already observed in axons of nerve ganglia in the pancreas 48 hours (early stage) after streptozotocin treatment. These changes were hardly detected at the light microscopic level and VIP-like immunoreactivities were seen in nerves and fibers in such pancreas. The nerve ganglia were almost absent in the diabetic pancreas 6 months after streptozotocin treatment (late stage). Associated with the absence of nerve ganglia, nerves and fibers containing VIP-like immunoreactivities were also absent at this late stage. The findings indicated that the changes in the diabetic pancreas were neuropathic caused by metabolic disturbance after long standing diabetes and resulting absence of VIP-like immunoreactive nerves occurred. It was suggested from the present study that the changes in nerve ganglia began as damage at the ultrastructural level due to acute toxicity of the chemical at an early stage and then developed destruction and absence at a late stage.     

海藻溴酚化合物对糖尿病大鼠抗氧化水平的影响

目的:本研究通过建立糖尿病大鼠动物模型,观察海藻溴酚化合物A、B对糖尿病大鼠机体抗氧化水平的影响。方法:采用STZ注射法制作糖尿病(DM)大鼠模型,随机分为空白对照组、糖尿病模型组、化合物A低剂量组及高剂量组、化合物B低剂量组及高剂量组,灌胃给药12周。12周末处死大鼠,测肾匀浆中谷胱甘肽过氧物酶(GSH-Px)的活力及丙二醛(MDA)的含量;并采用透射电镜观察大鼠肾组织的病理改变。结果:与空白对照组相比,糖尿病模型组肾组织匀浆中GSH-Px活力下降,MDA含量升高,差异有统计学意义(P<0.05)。各干预组中GSH-Px的活力较糖尿病模型组有升高的趋势,MDA含量有下降趋势。电镜下各干预组肾小球及肾小管病变较糖尿病组减轻,且高剂量组优于低剂量组。结论:溴酚化合物A、B能提高糖尿病大鼠机体抗氧化水平,并能一定程度的改善肾脏病理改化,但其具体机制有待进一步探讨。     

糖尿病肾病动物模型的研究进展

糖尿病肾病是终末期肾衰的主要原因,也是糖尿病致命的重要原因。但是糖尿病肾病的致病机制迄今尚不完全明了,理想的动物模型无疑可对糖尿病肾病的研究提供重要线索。糖尿病肾病动物模型包括诱发性、自发性和转基因等多种类型的动物模型,各种类型的动物模型在疾病的发生发展、病理生理变化等多个方面与人类糖尿病肾病具有相似的特征。应用这些模型有助于开展对糖尿病肾病的防治、发病机理、相关药物的开发等多方面的研究。     

终末期糖尿病肾病的血液透析与腹膜透析的比较研究

目的:探讨终末期糖尿病肾病患者接受不同透析方法的临床疗效。方法:40例终末期糖尿病肾病患者,按照透析方式分为血液透析和腹膜透析组,回顾性分析其临床资料。结果:血液透析与腹膜透析在血压控制,血糖,白蛋白、血总蛋白,肌酐、尿素氮水平,甘油三酯以及出血发生率等各项指标有其各自的优劣性,但是均可使患者获益,提高生存率,生存率比较无统计学差异。结论:及时、恰当的选择肾脏替代治疗,并在治疗过程中及时调整,甚或更换方案对终末期糖尿病肾病患者是有益的。     

Gene expression patterns in glucose-stimulated podocytes

To explore the mechanisms of podocyte injury under diabetic conditions, we performed an expression profile in glucose-stimulated podocytes. Differential gene expression profiles between conditionally immortalized mouse podocytes cultured in medium containing 5.6 and 30 mM glucose were measured with oligonucleotide microarrays. Of the genes identified, heme oxygenase-1, vascular endothelial growth factor-A, and thrombospondin-1 showed a consistently increased pattern, whereas angiotensin-converting enzyme-2 and peroxisomal proliferator activator receptor-γ were down-regulated. These results were validated using real-time PCR and western blotting in podocytes, and with immunohistochemistry on renal tissues from streptozotocin-induced diabetic rats. Not only is this the first report of gene expression profiling of podocyte injury under diabetic conditions, but the identified genes are promising targets for future diabetes research.