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目的 观察吡格列酮对2型糖尿病( Type 2 diabetes mellitus,DM2)大鼠血、尿单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)表达及肝脏组织结构和功能的影响.方法 正常对照组(NC组)以普通饲料喂养; DM2 SD大鼠模型采用高糖高脂饲料喂养联合小剂量链脲佐菌素( streptozotocin,STZ)注射的方法建立.将模型组大鼠随机分为糖尿病组(DM组)和吡格列酮组( PIO组),后者采用吡格列酮对PIO组大鼠进行干预治疗.8周后检测血糖、糖化血红蛋白(HbA1c)水平、生化指标及肝脏组织病理的改变情况,同时检血、尿MCP-1水平、尿白蛋白/尿肌酐( urinary albumin / creatinine ratio,ACR)、尿视黄醇结合蛋白( urinary retinol binding protein,URBP)的变化.结果 与NC组比较,DM组和PIO组第8周空腹血糖及HbAlc水平均明显升高,但DM组及PIO组间差异无统计学意义(P>0.05) ;第8周DM组与PIO组的尿ACR 、URBP 、血及尿MCP-1和肝脏纤维化程度均高于NC组(P<0.05),而PIO组4项指标较DM组明显降低,且UMCP-1与ACR呈正相关;病理显示,PIO组大鼠肝脏病变程度均较DM组明显减轻,肝组织MCP-1表达减少.结论 吡格列酮对DM2大鼠肝脏有明显的保护作用,其保护作用是独立于降糖作用之外的.其机制可能与其抑制肝组织MCP-1表达及其合成有关. 相似文献
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目的:分析糖维胶囊对2型糖尿病大鼠视网膜缺氧诱导因子-1α(HIF-1α)和核因子-κB(NF-κB)水平的影响。方法:健康雄性SD大鼠45只,10只作为正常组(NC组),其余使用链脲佐菌素(STZ)腹腔注射建立2型糖尿病大鼠模型(模型组),造模成功30只。成模后将模型组大鼠分为3个亚组,每组10只。糖尿病组(DM组)给予生理盐水灌胃,格列本脲治疗组(DM+G组)给予格列本脲20mg/kg灌胃,糖维胶囊治疗组(DM+T组)给予糖维胶囊150mg/kg灌胃治疗。连续灌胃4周后,取各组大鼠视网膜观察其病理改变并检测HIF-1α及NF-κB的mRNA及蛋白表达水平。结果:显微镜下观察,NC组视网膜所有细胞层清晰整齐地排列,在DM组中,视网膜水肿,DM+G组病变较轻,DM+T组未见明显新生血管形成,视网膜水肿显著减弱,神经节层整齐排列。与NC组相比,DM组HIF-1α、NF-κB mRNA及蛋白表达均明显上调(P0.05)。与DM组比较,DM+G组及DM+T组NF-κB mRNA及NF-κB、HIF-1α蛋白表达水平明显下降,且DM+T组NF-κB、HIF-1αmRNA和NF-κB蛋白下降较DM+G组更明显(P0.05)。结论:糖维胶囊能够影响HIF-1α、NF-κB因子表达,可明显改善大鼠2型糖尿病视网膜病变,为临床中西药联合治疗糖尿病提供一定依据。 相似文献
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黄连解毒汤对2型糖尿病大鼠细胞因子IL-4和IL-10水平的影响 总被引:13,自引:0,他引:13
目的:探讨黄连解毒汤对2型糖尿病大鼠血清抗炎细胞因子水平的影响,分析其改善胰岛素抵抗的作用机理。方法:观察黄连解毒汤对实验性2型糖尿病大鼠治疗前后血糖(FBG)、胰岛素(FINS)、血清白介素-4(IL-4)和白介素-10(IL-10)等指标的影响。结果:给予黄连解毒汤治疗的实验性2型糖尿病大鼠,其血清FBG水平显著低于模型组(P<0.01),FINS和模型组比较无显著差异;IL-4和IL-10水平明显高于模型组(均P<0.01)。结论:黄连解毒汤及其主要有效成分小檗碱具有提高2型糖尿病大鼠血清抗炎细胞因子IL-4和IL-10水平的作用,改善其慢性炎性反应和胰岛素抵抗。 相似文献
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Glucocorticoids Increase Repair Potential in a Novel in vitro Human Airway Epithelial Wounding Model 总被引:1,自引:0,他引:1
Airway epithelial damage is a cardinal feature of chronic asthma. Agents which enhance epithelial repair without triggering uncontrolled fibrosis of the mesenchyme would be predicted to be useful in the management of asthma. We have developed a repeat wound model using mucociliated human bronchial epithelial cell (HBEC) cultures to define the key pathways involved in airway epithelial repair, and to study the effects of potential therapeutic agents on epithelial repair in a chronic setting. We show that repair occurs primarily by cell migration to close a defect; this process requires activation of the EGF receptor (EGFR) and subsequent tyrosine kinase signalling. Migration is accompanied by up-regulation of CD44 in motile cells at the wound margins with proliferation of non-migrating cells adjacent to the wound area. In long-term studies β2 adrenoceptor agonists and phosphodiesterase (PDE) inhibitors have no effect on repair potential, in contrast chronic treatment with the glucocorticoid dexamethasone extends the lifespan of repeatedly wounded differentiated cultures. We suggest part of the beneficial effects of glucocorticoids in asthma is related to this ability to prolong repair potential following repeated episodes of epithelial injury. 相似文献
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黄芪多糖对链唑脲霉素诱导的2型糖尿病大鼠肾脏TGF-β_1表达的影响 总被引:4,自引:0,他引:4
目的:探讨黄芪多糖(APS)对链唑脲霉素(STZ)诱导的2型糖尿病(T2DM)大鼠早期肾脏病理改变的治疗作用及其机制。方法:雄性SPF级SD大鼠随机分为正常对照组(C组)、APS对照组(CA组)、T2DM组(DM组)及APS治疗组(DA组),每组8只。观察治疗前后各组大鼠血糖、葡萄糖耐量变化,肾脏组织形态学和转化生长因子β1(TGF-β1)表达等的变化。结果:DM组大鼠血糖显著高于C组,同时伴有明显的糖耐量异常(P<0.01),经APS治疗8周后,DA组血糖降低,糖耐量改善(P<0.01)。DM组大鼠的肾小球面积较正常大鼠大、系膜基质增加,肾小管管腔扩大,管壁变薄,肾小球基底膜(GBM)增厚,可见蛋白管型,APS治疗可减轻T2DM大鼠肾脏病理改变,降低TGF-β1的表达水平。结论:APS能够降低血糖,增强机体胰岛素敏感性,减轻DM肾脏病理损害。其机制与APS降低T2DM大鼠肾脏TGF-β1表达有关。 相似文献
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黄芪多糖对2型糖尿病大鼠肝脏CHOP表达的影响 总被引:3,自引:0,他引:3
目的:探讨黄芪多糖(APS)对2型糖尿病(T2DM)大鼠肝脏内质网应激标志蛋白CHOP表达的影响。方法:雄性SPF级SD大鼠44只,随机分为:空白对照组(C组)、单纯APS灌胃对照组(CA组)、T2DM模型组(T2DM组)、T2DM+APS治疗组(T2DM+APS组)。定期监测各组动物体重(BW)、随机血糖(随机BG)、空腹血糖(FBG)、空腹胰岛素(Fins)水平、口服葡萄糖耐量试验(OGTT),计算胰岛素抵抗指数(HO-MA-IR);用Westernblot法检测各组动物肝组织CHOP的表达水平。结果:T2DM组大鼠BW、随机BG、FBG、Fins、HOMA-IR均显著高于C组,同时伴OGTT异常(P0.01);T2DM+APS组大鼠BW、随机BG、FBG、HOMA-IR较T2DM组显著下降(P0.01),OGTT各时点BG较T2DM组均显著降低(P0.01);肝组织CHOP表达水平在T2DM组显著高于C组(P0.01),T2DM+APS组表达水平明显低于T2DM组(P0.05)。C组和CA组比较各项指标无显著性差异。结论:APS可显著降低T2DM大鼠血糖和改善胰岛素抵抗,其机制可能与APS减弱T2DM大鼠肝组织内质网应激蛋白CHOP表达有关。 相似文献
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Li Wang Jing Wu Hongwei Cao Rong Chen Nanyan Zhang Jianfang Fu Bin Gao Jing Zhang Rongrong Hou Chaowu Tang Qiuhe Ji 《Endocrine pathology》2009,20(4):227-234
Our experiment investigated the mRNA expression of intestinal gonadotropin-releasing hormone (GnRH), proglucagon (PG), and glucagon-like peptide 1 receptor (GLP-1R) in the jejunum, ileum, and colon of rats fed with high-fat diet and Goto-Kakizaki (GK) rats and revealed the physiological role of intestinal GnRH. We found that the GnRH and PG mRNA levels in high-cholesterol (HCh) diet were higher than in the control. However, the GnRH receptor (GnRHR) and GLP-1R mRNA levels did not differ significantly between HCh and control. The GnRH, PG, and GLP-1R mRNA levels in GK rats were lower, respectively, than those in control rats, while the GnRHR levels did not differ significantly between GK rats and control rats. There were no difference in GnRH, PG, GnRHR, and GLP-1R mRNA levels in the ileum and colon tissue between HCh and control rats. The GnRH mRNA levels of GK rats were lower than those in control rats; however, the PG, GLP-1R, and GnRHR levels did not differ significantly between GK and control rats. The GLP-1R mRNA levels of GK rats were lower than those in control rats. The GnRH mRNA expression showed positive correlation with PG mRNA expression in different intestinal sections. The GnRH level in the jejunum showed a significant effect on blood glucose level, while the PG level in the jejunum showed a significant effect on insulin level. This may imply that, compared with the ileum and colon, the jejunum had greater impact on glucose metabolism; furthermore, GnRH might interact with intestinal GLP-1 and GLP-2 through the paracrine and autocrine ways and then regulate glucose metabolism and insulin secretion. 相似文献
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Background and ObjectivesThe meta-analysis aimed to investigate the association of visceral fat area (VFA), waist circumference (WC), waist-hip ratio (WHR) and waist-height ratio (WHtR) with diabetic kidney disease (DKD) in type 2 diabetic patients.MethodsIncluded studies were searched from Pubmed, Embase, and the Cochrane Library before July 2020. We synthesized the pooled results of the above relationships by meta-analysis.ResultsFourteen cross-sectional studies were enrolled. The pooled results indicated there was a significant difference in continuous VFA, WC and WHR/WHtR between patients with DKD and those without DKD (standard mean difference, SMD, 0.24, 95% confidence interval, CI, 0.13–0.36, p = 0.000). For VFA, patients with DKD had higher VFA levels than those without DKD (SMD 0.27, 95% CI 0.03–0.50). In the WC subgroup, patients with DKD had higher WC levels than those without DKD (SMD 0.17, 95% CI 0.10–0.24); similarly, abdominal obesity (dichotomized WC) was significantly associated with an increase in the odds of DKD (expected shortfall, ES, 1.57, 95% CI 1.32–1.86). However, the association of continuous WHR/WHtR with DKD was not statistically significant (SMD 0.43, 95% CI −0.12 to 0.97), while we found this relationship was statistically significant when analyzed categorically (ES 1.58, 95% CI 1.22–2.06).ConclusionIn this meta-analysis, we found abdominal obesity parameters (continuous VFA, WC) were associated with increased odds of DKD, and type 2 diabetic patients with DKD were more likely to have abdominal obesity (categorized using WC or WHR/WHtR). 相似文献
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Takanobu Uchiyama Shunsuke Takata Hiroyuki Ishikawa Yoshihiko Sawa 《ACTA HISTOCHEMICA ET CYTOCHEMICA》2013,46(2):97-104
The dynamics of the renal lymphatic circulation in diabetic nephropathy is not fully elucidated. The present study evaluated the effect of diabetic nephropathy on the renal lymphatic circulation in streptozotocin (STZ)-induced type 1 diabetic mice (ICR-STZ) and in type 2 diabetic KK/Ta mice which were fed a high fat diet (KK/Ta-HF). The diabetic mouse kidneys developed edema because of the nephropathy. In control mice renal lymphatic vessels distributed in the cortex but rarely in the medulla while in ICR-STZ and KK/Ta-HF mice, there were many lymphatic vessels with small lumen in both cortex and medulla. Total numbers and areas of renal blood vessels in the diabetic mice were similar to those in the controls while the total numbers and areas of renal lymphatic vessels were larger in diabetic mice than in the controls. There were statistically significant differences in the numbers of lymphatic vessels with diameters of 50–100 µm between the ICR-STZ and the control ICR mice, and in the numbers of lymphatic capillaries with diameters smaller than 50 µm between the KK/Ta-HF and the control KK/Ta mice. The diabetic nephropathy may induce the lymphangiogenesis or result in at least the renal lymphatic vessel expansion. 相似文献
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目的 探讨钠尿肽系列对2型糖尿病早期肾损伤筛选的价值.方法 采用放免法检测正常对照组(37例)、2型糖尿病无肾病组(31例)、2型糖尿病早期糖尿病肾病组(26例)和2型糖尿病明显肾病组(23例)的C型利钠肽(CNP)与尿钠素(URO),分析各组间水平的变化,并进行钠尿肽系列与尿微量白蛋白与尿肌酐比值(MA/UCr)的相关分析.诊断性能采用受试者工作特征(ROC)曲线进行分析.结果 在2型糖尿病无肾病组、早期肾病组和明显肾病组间,随着肾损伤程度的加深,患者CNP与URO的浓度出现显著性的减低(P<0.001);而无肾病组CNP显著高于对照组(P <0.001).钠尿肽系列与MA/UCr间相关性分析显示:存在良好的负相关关系(P<0.001).而且在2型糖尿病早期阶段,CNP与URO在ROC曲线的线下面积为0.762和0.759,取临界值≤10.2 pg/mL和≤51.5 pg/mL时,其敏感性与特异性分别为:69.34%和70.23%、67.14%和71.29%,与MA/UCr有相近的诊断效率.结论 CNP与URO作为2型糖尿病早期肾损伤的筛查指标是有一定临床价值的. 相似文献
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目的:观察纤维蛋白原样-2(Fgl-2)凝血酶原酶在糖尿病大鼠肾脏中的表达及其病理变化,探讨Fgl-2凝血酶原酶介导的微血栓形成在糖尿病肾脏微血管病变中的作用。方法:实验大鼠随机分为正常对照组(NC组)和2型糖尿病组(T2DM组)。建立T2DM大鼠模型,分别于实验第19周、第23周、第28周处死大鼠,测定24h尿蛋白、血肌酐(Cr)、尿素氮(BUN)、相对肾重;HE、PAS、MASSON染色观察不同病程T2DM组及NC组大鼠的肾脏病理改变,检测大鼠肾脏微血管内血栓形成,计算单位肾小球面积内微血栓所占阳性面积比例;以逆转录PCR方法、免疫组织化学方法测定Fgl-2凝血酶原酶在T2DM大鼠肾脏组织细胞上的表达,并将其表达的平均光密度值与单位肾小球内微血栓阳性面积比例进行相关性分析。结果:T2DM组大鼠Cr、BUN、相对肾重、24h尿蛋白均升高,Fgl-2凝血酶原酶的表达量亦明显增多,主要表达在T2DM大鼠的肾小球毛细血管内皮细胞及肾间质微血管内皮细胞。病理组织学检查显示T2DM大鼠肾小球肥大、系膜扩张、肾小球基底膜增厚、细胞外基质增生、肾小球毛细血管微血栓形成,且微血栓阳性面积比例明显高于NC组。分析显示Fgl-2凝血酶原酶的蛋白表达量与单位肾小球内微血栓阳性面积比例呈正相关。结论:首次发现Fgl-2凝血酶原酶mRNA及蛋白质在T2DM大鼠肾脏中表达上调,与单位肾小球内微血栓阳性面积比例呈正相关,提示Fgl-2凝血酶原酶介导的肾脏内微血栓形成可能促进糖尿病肾病的发生和发展。 相似文献
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目的探讨2型糖尿病患者颈动脉硬化与尿微量白蛋白的关系。方法收集109例2005年至2008年在本院住院的2型糖尿病患者,采用彩色多普勒超声诊断仪10MHz高频探头检测患者双侧颈动脉,按超声检查结果分为4组:颈动脉正常组30例[双侧颈动脉内膜中层厚度(CIMT)〈0.9mm];颈动脉内膜增厚组30例(0.9mm≤CIMT≤1.3mm);稳定斑块组23例(斑块呈强回声,伴或不伴声影);不稳定斑块组26例(斑块呈略低回声,内部或周边/有强回声附着)。同时测定血肌酐、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL)、高密度脂蛋白胆固醇(HDL)、尿微量白蛋白(MAU),记录血压并计算体质量指数,比较四组患者MAU的差异。结果各组年龄、性别、体质量指数、血压、血肌酐比较差异无统计学意义(P〉0.05),MAU值各组与CIMT〈0.9mm组间差异有显著性(P〈0.01),尤其是不稳定斑块组与正常组差异最显著(P〈0.01),不稳定斑块组与稳定斑块组、内膜增厚组,稳定斑块组与内膜增厚组差异也有统计学意义(P〈0.05),不稳定斑块组与正常组在病程、FPG、Hba1C、TC、TG、LDL、HDL比较差异均有统计学意义(P〈0.05),稳定斑块组与内膜增厚组除TC、MAU差异有统计学意义外(P〈0.05),其余指标差异均无统计学意义(P〉0.05)。结论2型糖尿病患者颈动脉硬化程度与尿微量白蛋白水平呈正相关,MAU可预测2型糖尿病患者心血管疾病的风险。 相似文献
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Moreira T Cebers G Pickering C Ostenson CG Efendic S Liljequist S 《Neuroscience》2007,144(4):1169-1185
Hyperglycemia has been shown to worsen the outcome of brain ischemia in several animal models but few experimental studies have investigated impairments in cognition induced by ischemic brain lesions in hyperglycemic animals. The Goto-Kakizaki (GK) rat naturally develops type 2 diabetes characterized by mild hyperglycemia and insulin resistance. We hypothesized that GK rats would display more severe cerebral damage due to hyperglycemia-aggravated brain injury and, accordingly, more severe cognitive impairments. In this study, recovery of motor and cognitive functions of GK and healthy Wistar rats was examined following extradural compression (EC) of the sensorimotor cortex. For this purpose, tests of vestibulomotor function (beam-walking) and combined tests of motor function and learning (locomotor activity from day (D) 1 to D5, operant lever-pressing from D14 to D25) were used. EC consistently reduced cerebral blood flow in both strains. Anesthesia-challenge and EC resulted in pronounced hyperglycemia in GK but not in Wistar rats. Lower beam-walking scores, increased locomotor activity, impairments in long-term habituation and learning of operant lever-pressing were more pronounced and observed at later time-points in GK rats. Fluoro-Jade, a marker of irreversible neuronal degeneration, revealed consistent degeneration in the ipsilateral cortex, hippocampus and thalamus at 2, 7 and 14 days post-compression. The amount of degeneration in these structures was considerably higher in GK rats. Thus, GK rats exhibited marked hyperglycemia during EC, as well as longer-lasting behavioral deficits and increased neurodegeneration during recovery. The GK rat is thus an attractive model for neuropathologic and cognitive studies after ischemic brain injury in hyperglycemic rats. 相似文献
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目的通过检测糖尿病患者血浆中环氧化酶同工酶-2(COX-2)与血管内皮生长因子(VEGF)的变化,了解COX-2及VEGF水平的变化及其与患者尿蛋白定量之间的关系。方法收入51例2型糖尿病患者及47例年龄/性别匹配的健康志愿者,以ELISA法检测其血浆中COX-2与VEGF的水平,同时对研究对象的尿蛋白水平等肾功能指标进行检测,并对两组指标进行相关性分析。结果糖尿病患者血浆COX-2水平(55.58±8.84)ng/mL及VEGF水平(377.59±38.60)pg/mL均显著高于对照组[COX-2(0.89±0.27)ng/mL,VEGF(43.51±8.61)pg/mL](P均〈0.01);COX-2与VEGF之间存在正相关,差异有统计学意义(r=0.983,P〈0.01),COX-2及VEGF与患者尿蛋白之间均存在正相关,差异有统计学意义(COX-2与尿蛋白r=0.728,P〈0.01;VEGF与尿蛋白r=0.769,P〈0.01);COX-2及VEGF与患者血肌酐之间均存在正相关,差异有统计学意义(COX-2与血肌酐r=0.649,P〈0.01;VEGF与血肌酐r=0.619,P〈0.01)。结论2型糖尿病患者血浆中存在明显升高的COX-2及VEGF,并与患者尿蛋白水平及血肌酐水平存在相关性,提示COX-2及VEGF可能参与糖尿病肾病的发病过程。 相似文献
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DM2患者胰岛β细胞功能观察 总被引:1,自引:0,他引:1
目的:观察2型糖尿病(DM2)患者胰岛β细胞功能,探讨DM2人群胰岛β细胞功能的变化及不同浓度葡萄糖对胰岛分泌功能的影响。方法:对172例糖尿病患者停用药物24h后,口服75g葡萄糖行葡萄糖耐量实验(OGTT)及胰岛素释放试验(IRT)。根据我院172例DM2患者入院治疗情况,按其空腹胰岛素水平分为空腹低值组(A组),空腹低值有峰组(B组),空腹中值组(C组),空腹高值组(D组)及30例正常对照组(N组)。计算早期胰岛素分泌功能指数(△I30/△G30),基础胰岛素分泌指数(HOMAβ),修正胰岛β细胞功能指数(MBCI)。分析各组胰岛功能指数的变化。结果:DM2各组胰岛素水平较正常人组差异有显著性意义(P〈0.05)。DM2△I30/△G30在A、B组比较差异有统计学意义。MBCI在C、D组比较差异有统计学意义。HOMAβ在A、B及C、D组比较差异有统计学意义。△I30/△G30及HOMAβ在各组呈正相关。△I30/△G30及MBCI在各组均无相关性。结论:△I30/△G30、MBCI及HOMAβ可用于临床粗略评估胰岛β细胞功能,DM2患者在治疗前做IRT、OGTT对其诊断、治疗有重要的临床意义。 相似文献