血小板反应素1在STZ诱导大鼠糖尿病性视网膜病变的表达研究

探讨TSP1表达在糖尿病视网膜病变中的作用和机制,为治疗和预防糖尿病视网膜病变提供新的实验和理论依据。用链脲佐菌素(STZ)腹腔注射建立糖尿病模型8周后,采用免疫组织化学、RT-PCR及实时荧光定量PCR法,分析TSP1在早期链尿佐菌素诱导的糖尿病SD大鼠视网膜中的表达。结果显示在早期糖尿病大鼠的视网膜表面血管、神经节细胞层、内外核层中均有明显的TSP1表达,糖尿病视网膜组TSP1 mRNA表达要高于对照组,其中实时荧光定量PCR CT值的结果显示糖尿病组TSP1 mRNA表达量较对照组要高约3．48倍,二组间差别有显著性意义(P<0．01),提示TSP1在视网膜组织中的表达与糖尿病视网膜病变的发生密不可分,TSP1表达的增加可能在糖尿病视网膜病变的发生和发展中起重要作用。     

波动性高糖对乳鼠心肌细胞肥大的影响

目的 探讨波动性糖环境对体外培养的乳鼠心肌细胞肥大的影响.方法 取出生后2天SD大鼠乳鼠心脏,采用胶原酶消化法获取心肌细胞,进行心肌细胞原代培养.常规培养心肌细胞72h,待细胞搏动良好,将其随机分为3组:①对照组:给予稳定的糖浓度(5.5mmol/L);②高糖组:给予稳定高糖浓度(25.5mmol/L);③波动性糖组:波动性糖浓度为5.5mmol/L和25.5mmol/L,每12h交替,其他培养条件保持一致.Bradford法检测各组细胞总蛋白质含量;计算机细胞图像分析系统测量单个细胞的体积;采用3H-亮氨酸掺入法,用液闪仪测定心肌细胞蛋白质合成速率.结果 1.高糖组和波动性糖组与对照组相比心肌细胞蛋白含量均增加,波动性糖组与高糖组相比二者增加的数值相近.2.高糖组和波动性糖组与对照组相比心肌细胞体积均有明显增加.3.高糖组与波动性糖组与对照组相比均有蛋白合成的增加.波动性糖组与高糖组相比没有显著性差异.结论 波动性糖有促进心肌细胞肥大的作用,其作用强度与单纯性高糖相仿.在糖尿病心肌病中,波动性糖也是引起心肌细胞肥大、心肌顺应性下降的原因之一.提示临床治疗糖尿病患者时,除了要控制血糖防止血糖过高,而且还要保持血糖的稳定,减少血糖波动所导致的心肌损害.     

Genetic aberrations in macroautophagy genes leading to diseases

The catabolic process of macroautophagy, through the rapid degradation of unwanted cellular components, is involved in a multitude of cellular and organismal functions that are essential to maintain homeostasis. Those functions include adaptation to starvation, cell development and differentiation, innate and adaptive immunity, tumor suppression, autophagic cell death, and maintenance of stem cell stemness. Not surprisingly, an impairment or block of macroautophagy can lead to severe pathologies. A still increasing number of reports, in particular, have revealed that mutations in the autophagy-related (ATG) genes, encoding the key players of macroautophagy, are either the cause or represent a risk factor for the development of several illnesses. The aim of this review is to provide a comprehensive overview of the diseases and disorders currently known that are or could be caused by mutations in core ATG proteins but also in the so-called autophagy receptors, which provide specificity to the process of macroautophagy. Our compendium underlines the medical relevance of this pathway and underscores the importance of the eventual development of therapeutic approaches aimed at modulating macroautophagy.     

Effect of nano extracts of olea europaea leaves,ficus carica and liraglutide in lipidemic liver of type 2 diabetic rat model

The study aimed to evaluate the impact of Ficus carica mixture and Olea europaea leaf nano extracts, and liraglutide, on liver tissue and serum lipids in type 2 diabetic male albino rat model. Forty rats were divided equally into 4 groups were used. Group 1 was the non-diabetic control group. The animals in Groups 2–4 was injected intraperitoneally with a single dose of 60 mg/kg b.w. Streptozotocin to induce a diabetic rat model. Group 2 served as a positive control for diabetes. 0.02 mg/kg b.w./day of Liraglutide gave to groups 3 and 4 and 4.8 ng/ml × 10⁵ b.w./day of a mixture of the nano extracts, respectively. Eight weeks after treatment, the animals were sacrificed. Blood was collected for glucose analysis and serum low-density lipoprotein, high-density lipoprotein, total cholesterol, and triglycerides analysis, and the livers processed for histopathological examination. The elevated lipid profiles and blood glucose levels in diabetic group (Group 2) were significantly reduced (p < 0.001) following the administration of liraglutide and nano extracts in Groups 3 and 4. Progressive fatty acid changes were found in the liver sections, indicated by the deposition of various sizes of lipid droplets in most liver lobules, along with patchy hepatocyte necrosis. These pathological changes were ameliorated in the liraglutide- and nano-extract-treated rats. Treatment with the nano extracts resulted in significant power assays associated with recovery of hepatic histology and functional alterations, compared to liraglutide treatment.     

Methylglyoxal induces apoptosis through activation of p38 MAPK in rat Schwann cells

The formation of glucose-derived methylglyoxal (MG), a highly reactive dicarbonyl compound, is accelerated under diabetic conditions. We examined whether MG was capable of inducing apoptosis in Schwann cells (SCs), since recent studies have suggested a potential involvement of apoptotic cell death in the development of diabetic neuropathy. MG induced apoptosis in SCs in a dose-dependent manner, accompanied by a reduction of intracellular glutathione content and activation of the p38 MAPK. Inhibiting the p38 MAPK activation by SB203580 successfully suppressed the MG-induced apoptosis in SCs. Aminoguanidine and N-acetyl-l-cysteine also inhibited the MG-induced p38 MAPK activation and apoptosis along with restoration of the intracellular glutathione content. These results suggest a potential role for MG in SC injury through oxidative stress-mediated p38 MAPK activation under diabetic conditions, and it may serve as a novel insight into therapeutic strategies for diabetic neuropathy.     

Intra- and extraganglionic peripheral cholinergic neurons in the urogenital organs of the cat

Summary The distribution of cholinergic neurons in the urinary tract and male genital organs of the cat was studied by a histochemical method for acetylcholinesterase. In addition to cell clusters in autonomic ganglia (intraganglionic cells), isolated extraganglionic cholinergic cells were found within the innervated tissues, usually in association with nerve trunks and blood vessels. Smaller neural cells with multiple axonal processes, identical to Cajal's interstitial cells, were found in the meshes of the terminal nerve plexus in smooth muscle, lamina propria and vascular wall.It is concluded that peripheral cholinergic neurons, like their adrenergic analogues, are arranged as a short intraganglionic, a shorter extraganglionic, and a terminal system of neurons.Supported in part by grants 10465 and 11285 from the USPHS and the Henry C. Buswell Urology Research Fund.     

The heme precursor delta-aminolevulinate blocks peripheral myelin formation

Delta-aminolevulinic acid (δ-ALA) is a heme precursor implicated in neurological complications associated with porphyria and tyrosinemia type I. Delta-ALA is also elevated in the urine of animals and patients treated with the investigational drug dichloroacetate (DCA). We postulated that δ-ALA may be responsible, in part, for the peripheral neuropathy observed in subjects receiving DCA. To test this hypothesis, myelinating cocultures of Schwann cells and sensory neurons were exposed to δ-ALA (0.1–1 mM) and analyzed for the expression of neural proteins and lipids and markers of oxidative stress. Exposure of myelinating samples to δ-ALA is associated with a pronounced reduction in the levels of myelin-associated lipids and proteins, including myelin protein zero and peripheral myelin protein 22. We also observed an increase in protein carbonylation and the formation of hydroxynonenal and malondialdehyde after treatment with δ-ALA. Studies of isolated Schwann cells and neurons indicate that glial cells are more vulnerable to this pro-oxidant than neurons, based on a selective decrease in the expression of mitochondrial respiratory chain proteins in glial, but not in neuronal, cells. These results suggest that the neuropathic effects of δ-ALA are attributable, at least in part, to its pro-oxidant properties which damage myelinating Schwann cells.     

前列地尔联合尿激酶治疗糖尿病肾病尿蛋白的临床观察

目的:观察短期应用注前列地尔注射液、前列地尔注射液联合小剂量尿激酶对Ⅳ期糖尿病肾病患者尿蛋白的影响。方法:选取我院2005年1月～2009年12月的Ⅳ期糖尿病肾病住院患者548例,均采取强化控制血糖、血压,低蛋白饮食等基础治疗,分为前列地尔治疗组216例、前列地尔联合尿激酶治疗组332例,给予14天短期输液治疗,测定治疗前后24小时尿蛋白。结果:两组患者治疗前年龄、性别组成、糖尿病病程、血糖、血压、血脂、尿蛋白、肾功能等各项指标无显著差异。两组治疗前后各自比较,单独应用注前列地尔注射液、前列地尔注射液联合小剂量尿激酶,均可有效减少糖尿病肾病24小时尿蛋白排泄,但前列地尔注射液联合小剂量尿激酶改善尿蛋白排泄的效果较单独应用注前列地尔更显著(p<0.05),有效率更高(88.2%vs.75.4%,p<0.05);应用小剂量尿激酶未见眼底、皮肤、黏膜出血等不良反应,无凝血功能异常发生。结论:短期静脉应用前列地尔联合小剂量尿激酶治疗Ⅳ期糖尿病肾病,较单独使用前列地尔可更有效减少尿蛋白排泄,不增加眼底出血、皮肤出血、黏膜出血的风险,是一种降低糖尿病肾病尿蛋白水平的安全有效的治疗方法。     

交感皮肤反应在糖尿病周围神经病变诊断中的应用

糖尿病周围神经病变（Diabetic Peripheral Neuropathy,DPN）是糖尿病最常见的并发症之一。由于目前DPN发病机制不清楚、治疗效果不理想,故早诊断、早治疗显得至关重要。有研究指出交感神经皮肤反应（Sympathetic Skin Response,SSR）可作为评价2型糖尿病患者早期周围植物神经功能状态的指标。本文对SSR应用于DPN临床诊断中的检测技术、观测参数进行综述,发现多数研究中指出,在临床应用中SSR波形、波幅以及潜伏期指标的异常率常受到多种因素的影响、会发生很大波动,而电位曲线下面积减少值相对稳定。据此笔者建议在DPN早期临床诊断中以SSR电位曲线下面积减少作为关键参数,辅助参考SSR波形、波幅以及潜伏期指标进行诊断。