糖尿病血管平滑肌细胞增殖与线粒体关系的研究进展

糖尿病(diabetes mellitus,DM)是严重危害人类健康的全身性代谢疾病,常发生血液流变学、微循环和细胞代谢的紊乱,导致缺血、缺氧和组织水肿,进而引起血管和神经病变。血管病变常常是糖尿病病人致死、致残的主要原因。血管平滑肌细胞的增殖及表型改变是糖尿病引发动脉粥样硬化性疾病的显著特征,而线粒体在血管平滑肌细胞的增殖过程中起重要作用。因此,探讨糖尿病血管平滑肌细胞与线粒体的关系及机制为糖尿病血管性疾病的治疗提供重要的理论基础,有利于基础研究向临床试用药物研究的转化。     

血清胆红素、YKL-40、HMGB-1对糖尿病合并冠心病患者的临床意义

目的:探讨血清胆红素、人类软骨糖蛋白-39(YKL-40)、高迁移率族蛋白1(HMGB-1)对糖尿病合并冠心病患者的临床意义方法:选择2017年1月至2018年12月我院接诊的190例2型糖尿病患者,根据是否合并冠心病分为单纯糖尿病组121例和糖尿病合并冠心病组69例,并选择同期在我院接受体检的100例健康者作为对照组。比较三组临床生化指标、血清胆红素、YKL-40、HMGB-1及不同病变支数、不同病变程度糖尿病合并冠心病组血清胆红素、YKL-40、HMGB-1的表达。结果:三组空腹血糖(FBG)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血清胆红素、YKL-40、HMGB-1比较差异均有统计学意义(P0.05);不同病变支数、病变程度糖尿病合并冠心病患者血清胆红素、YKL-40、HMGB-1比较差异均有统计学意义(P0.05);经两两Pearson线性相关性分析结果显示,血清胆红素和Gensini评分呈负相关(r=-0.812,P0.01),YKL-40、HMGB-和Gensini评分正相关(r=0.873、0.801,P0.01)。结论:在糖尿病合并冠心病患者中,血清胆红素的表达明显降低,YKL-40、HMGB-1明显升高,且随着冠脉病变程度的加重变化更明显,本研究也为后期血清胆红素、YKL-40、HMGB-1在该病的早期诊断、预防、治疗效果评价等方面提供了依据     

颈动脉斑块LRNC特征可诊断2型糖尿病患者急性脑梗死的风险

2型糖尿病可能加重颈动脉斑块的易损性并增加缺血性中风的风险,关于2型糖尿病患者伴有颈动脉斑块特征的急性中风亚型鲜有研究报道。本研究旨在探讨2型糖尿病患者颈动脉斑块特征与MRI确定的急性脑梗死病变特征之间的关系。本研究以颈内动脉区急性脑血管病患者为研究对象,所有患者分为2型糖尿病组和非2型糖尿病组,分别行颈动脉和脑部MRI扫描,测定同侧颈动脉斑块的形态和特征,以及颅内和颅外颈动脉狭窄。基于中风亚型和急性脑梗塞病变模式对患者进行评估。研究结果表明,与非2型糖尿病患者相比,2型糖尿病患者颈动脉型IV-VI病变的患病率更高,斑块负荷更大,以及富脂质坏死核(LRNC)更大。在有症状的颈动脉LRNC患者中,与非2型糖尿病组相比,2型糖尿病组颈内动脉区出现较多的伴有大穿孔动脉梗塞形态和较大的急性脑梗塞。LRNC%>23.5%的颈动脉斑块是2型糖尿病患者存在颈动脉狭窄的急性脑梗塞病变的独立危险因素。颈动脉斑块特征的量化,尤其是MRI诊断的富脂质坏死核对中风风险具有潜在应用价值。     

MiR‐802 causes nephropathy by suppressing NF‐κB‐repressing factor in obese mice and human

Obesity is associated with significant microvascular complications including renal injuries and may induce end‐stage renal disease. Emerging studies have demonstrated microRNAs (miRNAs) are potential mediators in the pathophysiological process of nephropathy. The present study aimed to investigate the role of miR‐802 in obesity‐related nephropathy and potential molecular mechanisms. Through utilizing obese mouse model and human subjects, we explored the therapeutic benefits and clinical application of miR‐802 in protecting against nephropathy. Renal miR‐802 level was positively correlated with functional parameters, including blood urea nitrogen and creatinine in obese mice. Specific silencing of renal miR‐802 improved high fat diet (HFD)‐induced renal dysfunction, structural disorders and fibrosis. The up‐regulated inflammatory response and infiltrated macrophages were also significantly decreased in miR‐802 inhibitor‐treated obese mice. Mechanistically, miR‐802 directly bond to 3?‐UTR of NF‐κB‐repressing factor (NRF) and suppressed its expression. In clinical study, the circulating miR‐802 level was significantly increased in obese subjects, and positively correlated with plasma creatinine level but negatively correlated with creatinine clearance. Taken together, our findings provided evidence that miR‐802/NRF signalling was an important pathway in mediating obesity‐related nephropathy. It is a possible useful clinical approach of treating miR‐802 inhibitor to combat nephropathy.     

超声对早期糖尿病肾病的诊断价值及肾动脉血流阻力指数与血清hs-CRP、VEGF的关系分析

目的:研究彩色多普勒超声对早期糖尿病肾病的诊断价值及肾动脉血流阻力指数与血清超敏C反应蛋白(hs-CRP)、血管内皮生长因子(VEGF)的关系。方法:选取从2017年2月～2018年2月兰州大学第二医院收治的早期糖尿病肾病患者50例记为病变组,另取同期于该院进行体检的健康人员50例记为对照组。分别对两组人员进行彩色多普勒超声检查,比较肾血流参数。采用酶联免疫吸附法检测两组人员血清hs-CRP、VEGF水平,并作指标间的相关性分析。结果:病变组肾主动脉、肾锥体两侧叶间动脉、肾段动脉的收缩期峰值速度、舒张期最低速度较对照组降低,病变组肾主动脉、肾锥体两侧叶间动脉、肾段动脉的阻力指数较对照组升高(均P0.05)。病变组血清hs-CRP、VEGF水平较对照组升高(均P0.05)。经Pearson相关性分析显示:早期糖尿病肾病患者肾主动脉、肾锥体两侧叶间动脉、肾段动脉的血流阻力指数与血清hs-CRP、VEGF均呈正相关关系(均P0.05)。结论:彩色多普勒超声应用于早期糖尿病肾病的诊断价值较高,且肾动脉血流阻力指数与血清hs-CRP、VEGF密切相关,临床工作中通过联合检测血清hs-CRP、VEGF,从而有助于早期糖尿病肾病的诊断。     

Effect of Olea europaea leaves extract on streptozotocin induced diabetes in male albino rats

The present study was aimed to evaluate the effect of olive (Olea europaea) leaves extract on streptozotocin (STZ)-induced diabetic male rats. The experimental rats were divided into six groups. Rats of the first group were served as normal controls. Rats of the second group were diabetic control. The third and fourth groups were diabetic rats, treated with olive leaves extract at low and high doses respectively. The fifth and sixth groups were non diabetic rats, subjected to olive leaves extract at the same doses given to the third and fourth groups respectively. The minimum of body weigh gain was noted in diabetic rats of the second group. the levels of serum glucose, insulin, total protein, albumin, triglycerides, cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), creatine kinase (CK), lactate dehydrogenase (LDH) and malondialdehyde (MDA) were significantly increased, while the levels of high density lipoprotein cholesterol (HDL-C), superoxide dismutase, (SOD) glutathione (GSH) and catalase (CAT) were statistically decreased in diabetic rats of the second group. The levels of liver insulin receptor substrate 1 (IRS1) and insulin receptor A (IRA) were significantly declined in diabetic rats of the second group. The diabetic pancreatic sections from diabetic rats of the second group showed several histopathological changes. Administration of low and high doses of olive leaves extract improved the observed physiological, molecular and histopathological alterations. Collectively, the obtained results confirmed that the protective effects of olive leaves extract are attributed to the antioxidant activities of olive leaves extract and its active constituents.     

Novel nonapeptide GLP (28–36) amide derivatives with improved hypoglycemic and body weight lowering effects

Glucagon-like peptide-1 (GLP-1) has emerged as a major therapeutic target for the treatment of type 2 diabetes. The nonapeptide GLP-1 (28–36) amide is one of the biological C-terminal products of GLP-1 modified by the neutral endopeptidase (NEP) 24.11 with limited hypoglycemic activity. In this study, we focused on the modification of GLP-1 (28–36) amide for the first time and synthesized a series of GLP-1 (28–36) amide analogues. Results of biological activity evaluation in INS-1 cell, STZ-induced diabetic and diet induced obesity (DIO) mice indicated that S3 as a promising candidate to treat type 2 diabetes and obesity.     

2型糖尿病模型小鼠造模时间的选择

目的:分析不同时期的2型糖尿病小鼠血生化指标及心肌和肾脏的病理变化情况,为选择2型糖尿病模型小鼠造模时间提供依据。方法:32只健康雄性ICR小鼠高脂饲料喂养6周后,腹腔注射链脲佐菌素(STZ,30mg/kg),连续5d,制备糖尿病模型。9d后测空腹血糖(FBG),高于11.1mmol/L视为糖尿病模型。分别于成模后第4、6、8周处死一组小鼠。另取8只雄性ICR小鼠作为对照组,常规饲料喂养,于糖尿病组小鼠成模后第8周处死。分析小鼠生化及病理情况:①心脏、肾脏脏器系数计算;②血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酐(Cr)和尿素氮(BUN)含量测定;③HE染色观察心肌和肾脏组织病变的整体情况;Masson染色观察心肌组织纤维化情况;PAS染色观察肾脏组织病理变化。结果:与对照组小鼠进行比较,第4、6、8周的糖尿病小鼠心脏器系数升高,血清LDH、CK升高,病理组织学见心肌细胞肥大,纤维化;肾脏脏器系数升高,肾功能肌酐(Cr)、尿素氮(BUN)显著升高,病理组织学见肾小球肥大,肾小管基底膜增厚,管腔萎缩。结论:第6周糖尿病小鼠相关生化病理指标改变相对明显且饲养时间相对较短,故2型糖尿病模型小鼠造模后第6周是进行药物干预和病理、生理、生化等研究的最佳时间。     

香椿子正丁醇提取物改善糖尿病肾病肾小球内皮细胞炎症及机制研究

为研究香椿子正丁醇提取物(n-butyl alcohol extract of Toona sinensis,NBAE)对糖尿病肾病肾小球内皮细胞炎症的作用及机制,采用Wistar雄性大鼠,STZ注射造模,成功后分为DN组、DN+NBAE干预组,另设对照组。8周后取血测生化指标,取肾脏行HE和PAS染色,并行免疫组化检测MCP-1、ICAM-1、磷酸化p65的表达。以高糖(HG)、HG+NBAE、HG+NF-κB阻断剂吡咯烷二硫基甲酸盐(pyrrolidine dithiocarbamate,PDTC)刺激肾小球内皮细胞,采用Western blot法检测相关蛋白的表达。结果显示,与DN组大鼠相比,DN+NBAE组大鼠血糖明显降低,肾脏损伤减轻,相关蛋白表达均减少。细胞水平,NBAE明显降低MCP-1、ICAM-1的表达,差异具有统计学意义(P <0. 01),各指标改变情况与PDTC处理组类似。这表明NBAE明显改善DN肾小球内皮细胞的炎症,推测可能与抑制NF-κB信号通路有关。