罗格列酮对实验性慢性环孢素肾病的作用

目的 探讨罗格列酮（RSG）对慢性环孢素肾病（CCN）大鼠模型的肾保护作用。 方法 低盐饮食基础上建立CCN大鼠模型，其中1组模型鼠用RSG同时灌胃。分别在实验开始后第14天和第35天处死动物，检测血浆和肾组织血管紧张素Ⅱ（AngⅡ）、AngⅡ1型受体(AT1R)、转化生长因子β1(TGF-β1)、细胞外调节蛋白激酶（p-ERK）、α-SMA和纤连蛋白（FN）的表达。在体外用不同浓度的CsA和RSG孵育NRK细胞。RT-PCR检测肾皮质TGF-β1，Western印迹分析检测FN、AT1R、p-ERK水平。 结果 RSG可改善环孢素A导致的大鼠肌酐清除率的下降[（0.586±0.094）比(1.072±0.105)ml&#8226;min^-1&#8226;kg^-1，P < 0.01]、血浆和肾组织AngⅡ水平增加（P < 0.01）、肾间质单核细胞浸润（P < 0.01）、肾间质纤维化（1.707±0.019 比 2.335±0.022，P < 0.01）、肾组织α-SMA表达增加（P < 0.01）、肾皮质TGF-β1 mRNA水平增加（P < 0.01）、NRK细胞FN、AT1R和p-ERK蛋白水平增加（P < 0.05）。 结论 RSG可能通过减轻炎细胞浸润、影响AngⅡ作用和下调TGF-β1等途径减轻CsA所致的肾组织损伤。     

酒石酸罗格列酮对2型糖尿病患者颈动脉内膜中层厚度作用的分析

目的:探讨酒石酸罗格列酮(噻唑烷二酮类药物)抑制动脉粥样硬化的作用。方法:60例2型糖尿病患者服用罗格列酮4mg/d,观察期3个月。通过B型超声仪检测治疗前后颈动脉内膜中层厚度(IMT)及相关生化指标的变化。结果:患者服用罗格列酮3个月后,其IMT值(0.78±0.14)同治疗前(0.84±0.14)比较明显的降低(P<0.001),且IMT值与胰岛素抵抗指数(IAI)呈正相关(r=0.31,P<0.05)。结论:酒石酸罗格列酮可能通过降低胰岛素抵抗以及发挥抗炎抗细胞增殖作用,对2型糖尿病早期动脉粥样硬化病变具有一定的抑制作用。     

噻唑烷二酮类药物治疗2型糖尿病的有效性及安全性

噻唑烷二酮类药物是一类新型的治疗2型糖尿病的药物,通过提高机体对胰岛素的敏感性来达到良好控制血糖的作用.噻唑烷二酮类药物还可以有效地降低2型糖尿病患者血中低密度脂蛋白胆固醇、C-反应蛋白、基质金属蛋白酶-9、纤溶酶原激活物抑制剂-11的水平等,提高高密度脂蛋白胆固醇水平,改善血管内皮功能,减少2型糖尿病患者发生心血管疾病的风险.噻唑烷二酮类药物不良反应发生率低,安全性良好.     

噻唑烷二酮类治疗溃疡性结肠炎疗效的荟萃分析

目的采用Meta分析方法对噻唑烷二酮类药物(罗格列酮、吡格列酮)治疗溃疡性结肠炎的疗效进行系统评价。方法以"噻唑烷二酮"、"罗格列酮"、"吡格列酮"、"溃疡性结肠炎"、"随机对照试验"为检索词,检索PubMed、CNKI、WanFang Data、CBM、Google数据库,并追溯参考文献进行全面的文献检索。根据纳入与排除标准筛选文献,提取数据并评价质量,用Review Manager 4.3软件进行Meta分析,同时进行敏感性分析及发表偏倚的评估。结果本研究共纳入文献6篇,经Meta分析,噻唑烷二酮类能明显降低溃疡性结肠炎的疾病活动评分(UCAI)(WMD=-0.92,95%CI:-1.17~-0.66,P0.00001);噻唑烷二酮类明显增加溃疡性结肠炎的有效缓解人数(OR=12.31,95%CI:1.71~88.74,P=0.01);噻唑烷二酮类药物能明显改善溃疡性结肠炎的组织学分级,尤其是0~Ⅰ级(OR=2.71,95%CI:1.55~4.72,P=0.0004)。失效安全数结果显示,发表偏倚较小。敏感性分析研究表明结果稳定可靠。结论噻唑烷二酮类药物能显著提高溃疡性结肠炎的临床疗效。     

过氧化物酶体增殖物激活受体γ配体噻唑烷二酮类在脑缺血中的神经保护作用

噻唑烷二酮类物质为过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)的合成配体.PPARγ对多种类型组织均有一定的保护作用,研究涉及的领域包括糖及脂类代谢、癌症、动脉粥样硬化等.目前,噻唑烷二酮类物质在中枢神经系统疾病中的作用备受关注,如脑梗死、多发性硬化、阿尔茨海默病等.文章综述了脑缺血后PPARγ配体噻唑烷二酮类对抑制神经胶质细胞增殖、促进血管生成以及对抗神经元凋亡的作用.     

渥曼青霉素阻断罗格列酮对人巨噬细胞酰基辅酶A:胆固醇酰基转移酶-1表达的影响

目的:研究过氧化体增殖物激活型受体-γ(peroxisome proliferator activated receptors-γ,PPAR-γ)配体罗格列酮对巨噬细胞酰基辅酶A:胆固醇酰基转移酶-1(Acyl-CoA:cholesterol acyltransferase-1,ACAT-1)表达的影响及可能机制。方法:在RPMI 1640培养基中培养人单核细胞株(THP-1),加入佛波酯培养48h,细胞贴壁呈巨噬细胞样分化。将细胞分为空白对照组、不同浓度罗格列酮组和罗格列酮 渥曼青霉素(wortmannin)组,运用实时定量PCR和Western blot,观察巨噬细胞ACAT-1 mRNA和蛋白表达水平的变化。结果:罗格列酮可明显抑制ACAT-1 mRNA和蛋白的表达,且呈浓度依赖性;加入磷酯酰肌醇三磷酸激酶(phosphate dylinositol 3-kinase,PI3K)信号途径抑制剂渥曼青霉素后ACAT-1表达较罗格列酮组高,较空白对照组低。结论:PPAR-γ配体罗格列酮通过PI3K途径抑制ACAT-1表达发挥其抗动脉粥样硬化的作用。     

Acute effects of pioglitazone on glucose metabolism in perfused rat liver

Pioglitazone, a thiazolidinedone derivative, decreases insulin resistance and improves hyperglycemia in insulin-resistant obese and/or diabetic animals. However, the mechanisms by which hyperglycemia is improved are not well defined. We investigated the effects of pioglitazone on hepatic glucose metabolism using a perfused rat liver model. Perfusion with the buffer containing 1 – 10 μm pioglitazone for 20 min dose-dependently increased the hepatic fructose 2,6-bisphosphate content, a potent activator of 6-phosphofructo 1-kinase. The furctose 2,6-bisphosphate level after 20 min perfusion with 10 μm pioglitazone was 64.9± 14.5 pmol/mg ⋅ protein, significantly higher than the control (48.3±10.9 pmol/mg ⋅ protein). When the liver from a starved for 48 h rat was perfused with the buffer containing 2 mm lactate but no glucose, glucose was generated from lactate via the gluconeogenic pathway and flowed into the effluent perfusate at a constant rate of 31±0.6 μmol/g ⋅ liver/h. The addition of 10 μm pioglitazone decreased the glucose output rate to 19.3±3.8 μmol/g ⋅ liver/h. Dose-dependent inhibition of glucose output by pioglitazone was observed in the 1 – 10 μm dose range. These results indicate that pioglitazone may not only stimulate glycolysis but also inhibit gluconeogenesis in the liver. These acute and insulin-independent effects on hepatic glucose metabolism may partly account for the diverse anti-diabetic effects of pioglitazone. Received:13 May 1996 / Accepted in revised form: 14 April 1997     

吡格列酮治疗对糖尿病大鼠心肌的保护作用

目的探讨吡格列酮治疗对链脲佐菌素(STZ)糖尿病(DM)大鼠心肌的保护作用。方法雄性SD大鼠28只随机分为正常对照组(NC组),糖尿病组(DM组),吡格列酮治疗组(DP组):DM组制模后用STZ(65 mg.kg-1)制成DM大鼠模型,DP组用吡格列酮20 mg.kg-1.d-1灌胃连续8周。8周后测空腹血糖(FBS)、甘油三酯(TG)、总胆固醇(TC)、空腹胰岛素(FINS),并取左室心肌组织行电镜观察、免疫组化检测心肌组织中转化生长因子β1(TGF-β1)水平。结果与NC组比较,DM组与DP组FBS、TG、TC、TGF-β1均明显增高(P<0.05)、FINS降低(P<0.01);与DM组比较,DP组TG、TGF-β1均下降、FINS增加(P<0.05),但TC、FBS与DM组比较差异无统计学意义(P>0.05)。结论吡格列酮治疗可显著减轻DM大鼠心肌超微结构的病理改变,该药对DM大鼠心肌有一定保护作用。     

Rosiglitazone increases extravasation of macromolecules and endothelial nitric oxide synthase in skeletal muscles of the fructose-fed rat model

Reduced extravasation of macromolecules in skeletal muscle has recently been documented in the fructose-fed rat model, corroborating a hypothesis that a functional obliteration of muscle regional microcirculation might lead to hypertension and restrict access of nutrients and hormones to their target cells. The goal of this study was to assess the impact of a treatment with rosiglitazone on the reduced muscle vasopermeability observed previously in the fructose-fed rat model. Fructose-fed Sprague-Dawley rats were gavaged with rosiglitazone (10 micromol kg(-1) per day; n = 21) or the vehicle only (n = 19) for 3 consecutive weeks before assessing the extravasation of Evans Blue (EB) dye in vivo in distinct muscle groups. Relative to control group, rosiglitazone reduced mean arterial blood pressure (Delta = -16.7%, P < 0.001), plasma insulin (Delta= -39.1%, P < 0.05) and plasma triglyceride (Delta= -32.8 %, P < 0.01) concentrations in a significant manner. Plasma VEGF concentrations were significantly lower in the rosiglitazone-treated animals compared to the control animals (32.7 +/- 0.8 pg ml(-1) versus 46.1 +/- 1.2 pg ml(-1), P < 0.001). While no changes were observed in the lungs or the kidneys, fructose-fed rats treated with rosiglitazone had a 30-50% increase (P < 0.005) in the extravasation of EB regardless of the skeletal muscle group studied (rectus femoris, soleus, gastrocnemius lateralis, vastus lateralis and tibialis cranalis). In homogenates of skeletal muscles (vastus lateralis) of fructose-fed rats, rosiglitazone resulted in a significant increase in NO synthase (NOS) activity (Delta = +41.9 %, P < 0.003) as well as endothelial NOS immunoreactive mass (Delta = +37.8 %, P < 0.01) compared to the control animals. There was no change in the immunoreactive level of the nNOS isoform, the most abundant muscle isoform, or in the immunoreactive levels of VEGF. In conclusion, rosiglitazone appears to restore a vascular dysfunction previously documented in the skeletal muscle microcirculation, as evidenced by improved skeletal muscle vasopermeability and upregulation of the muscle endothelium-NO system in the fructose-fed rat model. These effects on muscle per se might also result in a partial improvement of the insulin resistance phenomenon by improving the distribution of nutrients and insulin to skeletal muscle. This effect appears to be independent of circulating levels of VEGF since changes in plasma concentrations of this permeability factor were lower in the rosiglitazone-treated group.