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1.
2型糖尿病在病理本质上是一种亚急性或慢性炎症性病变,其发生发展伴随着炎症反应,其中一个重要的发病机制是胰岛素抵抗.核因子-κB(nuclear factor-kappa b,NF-κB)是一类重要的核转录因子,参与了炎症和凋亡等病理生理过程,另外,NF-κB信号途径在胰岛素抵抗发生机制中有着非常重要作用.NF-κB信号转导通路的活化与炎症反应及胰岛素抵抗的发生密切相关.文章就NF-KB在糖尿病发生中的作用作一综述.  相似文献   

2.
目的:探讨解脲脲原体(Ureaplasma urealyticum)及其脂质相关膜蛋白(LAMPs)作用于人羊膜上皮细胞(HAECs)过程中白介素6(IL-6)、IL-8和肿瘤坏死因子α(TNF-α)的变化情况,阐明Toll样受体2(TLR2)的调控机制,明确解脲脲原体潜在的致病性。创新点:从解脲脲原体诱导炎症反应的分子机制入手,提出TLR2信号通路在其中的关键作用。方法:经TX-114处理萃取解脲脲原体获得LAMPs,将LAMPs和解脲脲原体分别感染HAECs,用酶联免疫吸附试验(ELISA)测定炎症细胞因子(IL-6、IL-8和TNF-α);采用实时聚合酶链反应(real-time PCR)测定TLR2 mRNA水平,用蛋白质印迹(Western blot)检测TLR2的表达量;经TLR2阻断剂(anti-h TLR2-IgA)处理后,测定相应炎症细胞因子。结论:解脲脲原体LAMPs能诱导HAECs的TLR2表达上调和炎症因子增加,从而发生炎症反应;TLR2受阻断后,炎症因子表达减少,炎症水平下降。TLR2在解脲脲原体LAMPs感染HAECs过程起关键作用。  相似文献   

3.
目的:研究和探讨梓醇对脂多糖(LPS)诱导的牛子宫内膜上皮细胞和小鼠子宫内膜炎的保护机制。创新点:首次证明梓醇对LPS刺激的牛子宫内膜上皮细胞炎症和LPS诱导的小鼠子宫内膜炎具有保护作用,其保护机制与抑制Toll样受体4/核因子κB(TLR4/NF-κB)炎症信号通路有关。方法:通过LPS的诱导,分别建立牛子宫内膜上皮细胞体外炎症模型和小鼠子宫内膜体内炎症模型,设置不同梓醇作用浓度梯度,采用酶联免疫吸附测定法(ELISA)、实时荧光定量聚合酶链式反应(q RT-PCR)、蛋白免疫印迹(western blot)和免疫荧光技术检测TLR4/NF-κB信号通路及其下游炎症因子的表达。结论:梓醇可以显著抑制TLR4和p65 NF-κB信号通路的表达,降低炎性因子肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和白细胞介素6(IL-6)的水平以及趋化因子CXCL8和CXCL5的表达,同时降低子宫组织髓过氧化物酶水平。通过在体内外炎症模型中加入梓醇,可以显著降低牛子宫内膜上皮细胞的炎症反应,有效保护小鼠体内子宫内膜的组织损伤。  相似文献   

4.
内脂素是近期才被发现的脂肪细胞因子,在人和小鼠的内脏脂肪组织含量较高,肥胖的程度与血浆内脂素水平成正比。内脂素具有胰岛素样的降血糖作用,并可以改善胰岛素抵抗。研究发现,内脂素与代谢综合症、代谢相关疾病(如糖尿病、肥胖、动脉硬化)以及炎症反应有重要关系。运动可以降低血浆内脂素水平,提高脂肪组织中内脂素mRNA的表达。内脂素可能是运动改善机体代谢状况、防治代谢疾病的信号分子。  相似文献   

5.
目的:以园蓝为研究材料,鉴定园蓝花青素提取物(GBBAEs)中的功能性成分的结构,建立脂多糖(LPS)诱导的体外炎症模型,并评价其抗炎作用和初步机制。创新点:首次探究了蓝莓花青素对建立的LPS诱导体外炎症模型的营养干预作用,并初步探究了发挥抗炎机制的作用通路。方法:将RAW 264.7细胞分为对照组(不作处理)和实验组(1μg/ml LPS刺激建模)。实验组进一步分为3个不同浓度组:400μg/ml GBBAEs组、800μg/ml GBBAEs组和1200μg/ml GBBAEs组。用酶联免疫吸附测定(ELISA)试剂盒检测一氧化氮(NO)、前列腺素E2(PGE2)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、干扰素γ(INF-γ)等炎症因子的释放量;用实时定量聚合酶链反应(RT-PCR)分析IL-1β、IL-6、TNF-α、环氧合酶-2(COX-2)及单核细胞趋化蛋白-1(MCP-1)的炎症相关基因m RNA的表达水平;用蛋白质印迹法(Western blot法)测定相关炎症蛋白COX-2和NF-κBp65表达水平。结论:试验结果表明,通过ELISA法测定GBBAEs可以显著性抑制NO、PGE2、IL-1β、IL-6、INF-γ等炎症因子的释放;RT-PCR分析阐明在LPS诱导的单核-巨噬细胞RAW 264.7中,GBBAEs可以显著性抑制IL-1β、IL-6、TNF-α、COX-2及MCP-1的炎症相关基因m RNA的表达水平。此外,Western blot法进一步显示GBBAEs对相关炎症蛋白COX-2和NF-κBp65表达具有明显抑制作用,进一步证实GBBAEs通过NF-κB机制通路来发挥抗炎作用。  相似文献   

6.
目的:评估安石榴苷对脂多糖诱导奶牛子宫内膜上皮细胞炎症损伤的保护作用,并初步探讨其作用机制。创新点:首次证明安石榴苷对脂多糖诱导奶牛子宫内膜上皮细胞炎症损伤具有保护作用,且此作用与核转录因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路的抑制相关。方法:用不同浓度的脂多糖(1、10、30、50和100μg/ml)刺激奶牛子宫内膜上皮细胞3、6、9、12和18 h,筛选出建立炎症损伤的最佳作用浓度和时间。安石榴苷预处理细胞2 h后用脂多糖刺激12 h,用逆转录聚合酶链式反应(RT-PCR)检测炎症因子白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、白细胞介素8(IL-8)及肿瘤坏死因子α(TNF-α)的表达。用蛋白质免疫印迹试验(Western blotting)的方法检测核因子κB抑制蛋白α(IκBα)、磷酸化的p65、p38、c-Jun氨基末端激酶(JNK)和细胞外调节蛋白激酶(ERK)的表达水平。结论:MTT结果显示,30μg/ml脂多糖刺激奶牛子宫内膜上皮细胞12 h能够造成细胞活力下降和形态改变(图2和3)。RT-PCR结果显示,安石榴苷预处理后炎症因子显著降低(图4)。Western blotting结果显示,安石榴苷预处理能显著抑制IκBα降解以及p65、p38、JNK和ERK的磷酸化表达水平(图5和6)。综上所述,安石榴苷对脂多糖诱导奶牛子宫内膜上皮细胞炎症损伤具有保护作用,在治疗奶牛子宫内膜炎中具有重要价值。  相似文献   

7.
对视黄醇结合蛋白4在胰岛素抵抗形成中的作用及其与运动关系的研究进展进行了综述研究。视黄醇结合蛋白4是将肥胖、2型糖尿病胰岛素抵抗联系起来的脂肪因子,视黄醇结合蛋白4遗传多态性亦与胰岛素抵抗的发生关系密切。视黄醇结合蛋白4能够通过抑制胰岛素信号蛋白诱导胰岛素抵抗。运动能够降低正常体重、肥胖、2型糖尿病对象的视黄醇结合蛋白4,改善胰岛素抵抗。  相似文献   

8.
目的:放创复合伤是一种以血管损伤和促炎细胞因子缺乏为特征的难愈性创伤。瘦素(leptin)的直接应用在血管生成和炎症中起着重要作用。本研究构建了一种可持续稳定的leptin表达系统——leptin修饰的人胎盘来源间充质干细胞(HPMSCs/leptin),并探究其对经X射线辐照后的人脐静脉内皮细胞(HUVECs)的成血管潜能及周围炎症的影响和潜在机制。创新点:可持续稳定的leptin表达系统(HPMSCs/leptin)促进受X射线辐照后HUVECs的成血管潜能及外周炎症反应,有助于解决放创复合伤伤口愈合过程中血管损伤和促炎因子缺乏的问题。方法:利用慢病毒载体将leptin基因转染HPMSCs获得HPMSCs/leptin。采用X射线单次照射HUVECs,剂量为20 Gy。细胞迁移侵袭实验技术(Transwell)检测照射后HUVECs的迁移情况。在Transwell体系的基础上,建立HPMSCs与受辐照HUVECs共培养体系。CCK-8比色法测定细胞增殖。酶联免疫吸附法(ELISA)检测促炎细胞因子(粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-1α(IL-1α)、IL-6和IL-8)的分泌。实时荧光定量聚合酶链式反应(RT-qPCR)检测促血管生成因子(VEGF和bFGF)mRNA的表达。蛋白免疫印迹法(westernblot)检测核因子κB(NF-κB)和JAK/STAT信号通路的相关分子表达。结论:可持续稳定的leptin表达系统(HPMSCs/leptin)具有更好的细胞增殖、迁移和成血管潜能。HPMSCs/leptin单独培养和HPMSCs/leptin与受辐照HUVECs共培养体系中,促炎细胞因子的分泌增加与NF-κB和JAK/STAT信号通路的相互作用有关。HPMSCs/leptin可能促进X射线照射后HUVECs的成血管潜能和外周炎症反应。  相似文献   

9.
目的:放创复合伤是一种以血管损伤和促炎细胞因子缺乏为特征的难愈性创伤。瘦素(leptin)的直接应用在血管生成和炎症中起着重要作用。本研究构建了一种可持续稳定的leptin表达系统——leptin修饰的人胎盘来源间充质干细胞(HPMSCs/leptin),并探究其对经X射线辐照后的人脐静脉内皮细胞(HUVECs)的成血管潜能及周围炎症的影响和潜在机制。创新点:可持续稳定的leptin表达系统(HPMSCs/leptin)促进受X射线辐照后HUVECs的成血管潜能及外周炎症反应,有助于解决放创复合伤伤口愈合过程中血管损伤和促炎因子缺乏的问题。方法:利用慢病毒载体将leptin基因转染HPMSCs获得HPMSCs/leptin。采用X射线单次照射HUVECs,剂量为20 Gy。细胞迁移侵袭实验技术(Transwell)检测照射后HUVECs的迁移情况。在Transwell体系的基础上,建立HPMSCs与受辐照HUVECs共培养体系。CCK-8比色法测定细胞增殖。酶联免疫吸附法(ELISA)检测促炎细胞因子(粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-1α(IL-1α)、IL-6和IL-8)的分泌。实时荧光定量聚合酶链式反应(RT-q PCR)检测促血管生成因子(VEGF和b FGF)m RNA的表达。蛋白免疫印迹法(westernblot)检测核因子κB(NF-κB)和JAK/STAT信号通路的相关分子表达。结论:可持续稳定的leptin表达系统(HPMSCs/leptin)具有更好的细胞增殖、迁移和成血管潜能。HPMSCs/leptin单独培养和HPMSCs/leptin与受辐照HUVECs共培养体系中,促炎细胞因子的分泌增加与NF-κB和JAK/STAT信号通路的相互作用有关。HPMSCs/leptin可能促进X射线照射后HUVECs的成血管潜能和外周炎症反应。  相似文献   

10.
利用脂多糖(LPS)刺激小鼠小胶质细胞BV2,研究泽泻醇对炎症相关分子的抑制及机制.Griess法测定一氧化氮(NO)浓度,RT-PCR和Western blot法检测细胞外调节蛋白激酶(ERK)、p38、c-Jun氨基末端激酶(JNK)、蛋白激酶B(Akt)、基质金属蛋白酶3(MMP3)的变化.研究结果表明,泽泻醇不仅对LPS刺激小胶质细胞产生的NO有明显抑制作用,还能在mRNA与蛋白质水平抑制MMP3的表达,这种抑制与其对PI3K/Akt通路的干预相关.阐述了泽泻醇对小胶质细胞的抑制与PI3K/Akt通路的相关机制.  相似文献   

11.
胰岛素抵抗是运动科学研究领域的热点,对于胰岛素抵抗评价方法的选择对该类型研究的质量有着重要影响.胰岛素抵抗评价方法种类较多,可以根据研究类型、研究对象数量和指标检测方法等因素做出选择.稳态模型(HOMA)评估模式即是众多胰岛素抵抗评价方法的一种,是以基础水平的葡萄糖、胰岛素或C肽为参考,并以胰岛素抵抗指数的形式(HOMA-IR)对β细胞功能和胰岛素抵抗进行评价.本文从稳态模型评估模式的应用入手,对中文运动科学论文使用该模型的情况进行研究,分析该模型使用中出现的各种问题,以期为正确使用该模型提供参考和借鉴.  相似文献   

12.
目的:观察姜黄素对胰岛素抵抗(IR)大鼠糖脂代谢及血清脂肪细胞因子的影响,探讨姜黄素干预IR的作用机制。方法:采用高脂饲料喂养,建立IR大鼠模型。将IR大鼠随机分为3组:模型组、吡咯列酮组和姜黄素组。给药4周后测定空腹血糖、胰岛素、血脂、TN F-α、Leptin等指标。结果:模型组大鼠血清FIN S、TC、TG和LDL水平均较空白组显著升高,而ISI及HDL水平显著下降;血清TN F-α、Leptin及FFA水平也较空白组明显升高;用姜黄素干预后,大鼠ISI较模型组显著升高,血脂得到改善,FINS、TNF-α、Leptin及FFA水平均显著下降。结论:姜黄素可改善IR大鼠糖脂代谢紊乱,增加胰岛素的敏感性,其机制可能与其调节脂肪细胞因子TNF-α、Leptin的分泌有关。  相似文献   

13.
目的观察慢性充血性心力衰竭(CHF)患者的血胰岛素和糖代谢变化,并探讨依那普利对CHF患者胰岛素敏感性的影响。方法CHF患者69例,依那普利(n=37)(第一周10mg,1次/d,后三周20mg,1次/d)和地高辛(n=32)(第一周0.25mg,1次/d,后三周0.125mg,1次/d),治疗前和治疗4周后检测空腹血糖(FPG)、空腹血清胰岛素(FINS)和空腹血清C肽(CP)水平,并计算出FPG/FINS比值、胰岛素敏感性指数IAI值[IAI=-ln(FPG×FINS)]作为机体胰岛素敏感性评价指标,分别比较两组患者治疗前后的胰岛素敏感性变化。结果治疗4周后,依那普利组CHF患者的胰岛素敏感性显著增加,而地高辛组患者胰岛素敏感性无显著变化。结论依那普利有改善CHF患者IR的作用。  相似文献   

14.
Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ (PPARγ) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.  相似文献   

15.
目的探讨2型糖尿病(T2DM)患者胰岛素抵抗与微量白蛋白尿(MAU)的相关关系。方法将302名RDM患者根据尿白蛋白排泄率(UAER)进行分组。采用多因素相关和回归分析评价胰岛素抵抗指数(insulin resistance index,HOMA-IR)、李光伟指数(IAI)对UAER的影响。结果随着UAER的增加,HOMA—IR逐渐升高,IAI逐渐降低。多因素相关和回归分析显示,IAI与UAER显著负相关(P〈0.01)。结论2型糖尿病患者胰岛素抵抗是微量白蛋白尿的独立危险因素。  相似文献   

16.
Insulin is one of the most extensively studied protein hormones, and its structure and function have been elucidated in many vertebrate species, ranging from human to fish. Insulin-like peptides (ILPs) also have been found and characterized in different invertebrates, including nematodes, mollusks and insects. However, insect ILPs turned out to be a structurally diverse group encoded by large multi-gene families that are expressed in the brain and other tissues and serve functions different from vertebrate insulin. Recent physiological and genetic studies have revealed that, in different insect species, the conserved insulin signaling pathway plays a key role in the regulation of a variety of fundamental processes, such as metabolism, growth, reproduction and aging. Here, the structures, distributions, conserved signaling pathways, and physiological functions of insect ILPs are reviewed in detail.  相似文献   

17.
Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods: The rats were separated randomly into 6 groups: model group Ⅰ were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/(kg.d) simultaneously, while control group Ⅰ were fed normal food for 8 weeks; model group Ⅱ were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/(kg.d) orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNF-α), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed. Results: After 8 weeks, the liver in model group Ⅰ showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased (P〈0.05) compared with control group Ⅰ. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P〈0.05) compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels ofALT, AST, ALP, FINS and HOMA-IR were significantly increased (P〈0.05) in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group Ⅱ. Conclusion: Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.  相似文献   

18.
目的:观察诺和锐30特充对2型糖尿病患者血浆C-反应蛋白的影响。方法:选择80例2型糖尿病病人,随机分为诺和锐治疗组及诺和灵30R治疗组,诺和锐为餐前即刻皮下注射,诺和灵30R为餐前30min皮下注射,观察两组病人治疗前后餐前、餐后血糖及血浆C-反应蛋白(C-reactive protein,CRP)情况。结果:诺和锐治疗组餐后血糖水平低于诺和灵30R组(P〈0.01),诺和锐治疗组治疗后C反应蛋白水平明显低于诺和灵30R治疗组(P〈0.01)。结论:对于2型糖尿病患者,诺和锐疗效优于诺和灵30R,而且可以显著降低血浆CRP的水平。  相似文献   

19.
Insulin is a major protein hormone secreted by the β-cells of the pancreas and is important for the control of diabetes. Insulin is usually administered to diabetic patients through subcutaneous injection. This mode of therapy has certain inherent disadvantages such as local pain, itching and insulin lipodystrophy around the injection site. Hence, pharmaceutical scientists have been trying to design an oral delivery system for insulin. Many challenges are associated with the oral delivery of insulin, relating to the physical and chemical stability of the hormone, and its absorption and metabolism in the human body. Here we discuss various strategies for the oral delivery of insulin that are being tried out, as well as methods used to improve the absorption of orally consumed insulin and to reduce its degradation by digestive enzymes. K Gowthamarajan is on the faculty of the Department of Pharmaceutics in JSS College of Pharmacy, Ootacamund. His research interests are in the area of designing drug delivery systems for peptides and proteins. He is currently involved in research on pharmaceutical applications of plant polysaccharides. Giriraj T Kulkarni is on the faculty of the Department of Pharmaceutics in JSS College of Pharmacy, Ootacamund. Currently, he is involved in research on pharmaceutical and biotechnological applications of plant polysaccharides. He has authored a book ‘Biotechnology and its Applications in Pharmacy’ for undergraduate and postgraduate students of pharmacy.  相似文献   

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