非诺贝特和吡格列酮对代谢综合征大鼠血压及体重的影响

目的:探讨非诺贝特和吡格列酮对高果糖诱导的代谢综合征(MS)大鼠血压及体重的影响.方法:用高果糖饮食饲养SD大鼠构建Ms大鼠模型,将存活的大鼠随机分为空白对照组(n=8),代谢综合征模型组(n=39).又将代谢综合征模型组分为4个亚组:模型对照亚组(n=10),非诺贝特亚组(n=8),毗格列酮亚组(n=11),非诺贝特+吡格列酮哑组(n=10)分别单用非诺贝特和吡格列酮及二者合用干预.分析比较两种药物单用及合用,对MS大鼠收缩压、体重等的影响.结果:吡格列酮亚组干预后与干预前比收缩压降低(P<0.01),胰岛素敏感指数(ISI)升高(P<0.01).非诺贝特亚组干预后与干预前比收缩压、ISI变化均不明显(P>0.05).非诺贝特+吡格列酮亚组干预后与干预前比收缩压降低,ISI升高(P均<0.01),差异有统计学意义.干预后,各药物干预亚组与模型对照亚组问体重差异无统计学意义(P>0.05).结论:单用吡格列酮或合用非诺贝特干预明显改善MS大鼠胰岛素抵抗、降低收缩压,可更好地控制其心血管病的危险因素.     

过氧化体增殖物激活型受体α/γ激动剂对代谢综合征患者高敏C反应蛋白和基质金属蛋白酶9的影响

目的了解过氧化体增殖物型激活受体α/γ激动剂单用与联用对代谢综合征患者高敏C反应蛋白和基质金属蛋白酶9的影响。方法 256例代谢综合征患者随机分为基础治疗组、非诺贝特组、吡格列酮组、非诺贝特+吡格列酮组。所有患者进行生活方式干预及应用相应药物。在控制血压的基础上,基础治疗组加服安慰剂;非诺贝特组加服非诺贝特0.2 g,每日1次,睡前服;吡格列酮组加服吡格列酮15 mg,每日1次;非诺贝特+吡格列酮组按相同剂量加服上述2种药物。共干预24周。干预前后测定所有患者高敏C反应蛋白和基质金属蛋白酶9的浓度。结果干预前后各组的血清高敏C反应蛋白分别为:非诺贝特组6.32±1.65 mg/L和3.52±1.98 mg/L,吡格列酮组5.85±1.59 mg/L和3.33±1.16 mg/L,非诺贝特+吡格列酮组6.49±1.34 mg/L和2.47±0.91 mg/L;干预前后各组的基质金属蛋白酶9的浓度分别为:非诺贝特组179.3±54.9μg和L/144.9±30.8μg/L,吡格列酮组188.7±62.4μg/L和146.9±27.8μg/L,非诺贝特+吡格列酮组177.5±58.7μg/L和128.8±34.8μ...     

非诺贝特和吡格列酮对血管紧张素Ⅱ介导的心肌细胞肥大和凋亡的干预作用

目的 探讨过氧化物酶体增殖物激活型受体α和γ(PPARα和PPARγ)的配体非诺贝特、吡格列酮对血管紧张素Ⅱ(Ang Ⅱ)诱导的心肌细胞肥大、凋亡的干预作用,并观察其对凋亡相关基因Bcl-2/Bax表达变化的影响 .方法 分别以非诺贝特和/或吡格列酮预处理体外原代培养的新生大鼠心肌细胞24 h后,再加用Ang Ⅱ作用24 h.采用软件分析细胞表面积,用流式细胞仪检测细胞凋亡率,用Western-blot法观察凋亡相关基因Bcl-2/Bax的表达变化,逆转录聚合酶链反应检测PPARα和PPARγ的mRNA水平.结果 与Ang Ⅱ组比较,非诺贝特组、吡格列酮组及非诺贝特和吡格列酮组的心肌细胞表面积、细胞凋亡率及Bax蛋白的表达明显降低(P＜0.05),而 Bax蛋白的表达和Bcl-2/Bax蛋白水平比值显著增加(P＜0.05),非诺贝特组、吡格列酮组及非诺贝特和吡格列酮组间的上述指标差异无显著性(P＞0.05),非诺贝特组的PPARα mRNA和吡格列酮组的PPARγ mRNA表达增高.结论 PPARα和γ激活可逆转心肌细胞肥大,抑制心肌细胞凋亡,并能改变凋亡相关基因Bcl-2/Bax的表达,但PPARα、γ配体合用无叠加效应.     

非诺贝特和吡格列酮对血管紧张素Ⅱ介导的心肌细胞肥大和凋亡的干预作用

目的探讨过氧化物酶体增殖物激活型受体α和γ(PPARα和PPARγ)的配体非诺贝特、吡格列酮对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大、凋亡的干预作用,并观察其对凋亡相关基因Bcl-2/Bax表达变化的影响。方法分别以非诺贝特和/或吡格列酮预处理体外原代培养的新生大鼠心肌细胞24h后,再加用AngⅡ作用24h。采用软件分析细胞表面积,用流式细胞仪检测细胞凋亡率,用Western-blot法观察凋亡相关基因Bcl-2/Bax的表达变化,逆转录聚合酶链反应检测PPARα和PPARγ的mRNA水平。结果与AngⅡ组比较,非诺贝特组、吡格列酮组及非诺贝特和吡格列酮组的心肌细胞表面积、细胞凋亡率及Bax蛋白的表达明显降低(P<0.05),而Bax蛋白的表达和Bcl-2/Bax蛋白水平比值显著增加(P<0.05),非诺贝特组、吡格列酮组及非诺贝特和吡格列酮组间的上述指标差异无显著性(P>0.05),非诺贝特组的PPARαmRNA和吡格列酮组的PPARγmRNA表达增高。结论PPARα和γ激活可逆转心肌细胞肥大,抑制心肌细胞凋亡,并能改变凋亡相关基因Bcl-2/Bax的表达,但PPARα、γ配体合用无叠加效应。     

过氧化物酶体增殖物激活型受体α和γ配体对左心室压力超负荷大鼠心肌胶原重塑的影响

目的探讨过氧化物酶体增殖物激活型受体a和γ(PPARα和PPARγ)的配体非诺贝特、吡格列酮对左心室压力超负荷大鼠左心室肥厚过程中心肌胶原重塑的影响.方法雄性Wistar大鼠腹主动脉缩窄复制压力超负荷模型,术后48 h存活的40只随机分为手术组(CAA组)、非诺贝特组(F组,非诺贝特30 mg·kg-1·d-1)、吡格列酮组(P组,吡格列酮3 mg·kg-1·d-1)及非诺贝特和吡格列酮合用组(F加P组,非诺贝特30 mg·kg-l·d-1和吡格列酮3 mg·kg-1·d-1).以假手术组(SH组)为对照,在给药处理8周后观察左室质量指数(LVMI)以及心肌胶原容积分数(CVF),并采用逆转录聚合酶链反应(RT-PCR)检测左心室心肌Ⅰ、Ⅲ型胶原mRNA的表达水平.结果与SH组比较,CAA组的LVMI、CVF及Ⅰ、Ⅲ型胶原mRNA表达均明显增高(P＜0.05),F组、P组及F加P组的上述指标低于CAA组(P＜0.05);F组、P组及F加P组间各指标差异无统计学意义(P＞0.05).结论PPARα和γ信号通路激活能抑制压力超负荷大鼠的心肌胶原重塑.     

PPAR-γ在调节代谢综合征患者颈动脉重构的作用

目的探讨过氧化物酶体增殖物激活受体-γ(peroxisome proliferatoractivated receptor-y,PPAR-γ)在调节代谢综合征患者颈动脉重构的作用。方法把代谢综合征患者分为吡格列酮组和对照组,所有患者均给予降压、降胆固醇、降糖等基础治疗,吡格列酮组加用PPAR-γ激动剂-吡格列酮,对照组加用安慰剂干预。分析比较干预前后吡格列酮组患者颈动脉内中膜厚度及斑块阳性率的变化,以及干预后对照组和吡格列酮组患者在颈动脉内中膜厚度及斑块阳性率上的差异。结果与干预前比较,干预后吡格列酮组患者颈动脉IMT及斑块阳性率均显著降低:干预后,吡格列酮组患者斑块阳性率较对照组患者降低。结论 PPAR-γ激活后可改善代谢综合征组患者颈动脉重构,较基础治疗更显著地抑制其斑块形成。     

PPAR-γ在调节代谢综合征患者颈动脉重构的作用

目的探讨过氧化物酶体增殖物激活受体-γ(peroxisome proliferatoractivated receptor-y,PPAR-γ)在调节代谢综合征患者颈动脉重构的作用。方法把代谢综合征患者分为吡格列酮组和对照组,所有患者均给予降压、降胆固醇、降糖等基础治疗,吡格列酮组加用PPAR-γ激动剂-吡格列酮,对照组加用安慰剂干预。分析比较干预前后吡格列酮组患者颈动脉内中膜厚度及斑块阳性率的变化,以及干预后对照组和吡格列酮组患者在颈动脉内中膜厚度及斑块阳性率上的差异。结果与干预前比较,干预后吡格列酮组患者颈动脉IMT及斑块阳性率均显著降低:干预后,吡格列酮组患者斑块阳性率较对照组患者降低。结论 PPAR-γ激活后可改善代谢综合征组患者颈动脉重构,较基础治疗更显著地抑制其斑块形成。     

吡格列酮和非诺贝特对高脂饮食大鼠胰岛细胞内信号分子的影响

目的 观察吡格列酮和非诺贝特对高脂饮食大鼠胰岛内PPAR-α、-γ和细胞内信号分子的影响.方法 40只雄性SD大鼠随机分为4组:空白对照组(NC)、单纯高脂饮食组(HF)、高脂+非诺贝特组(FF)、高脂+吡格列酮组(FP).HE染色测定胰岛面积;免疫组织化学方法检测胰岛中各种蛋白的表达.结果 HF组胰岛面积、胰岛素、PPAR-γ、PPAR-α、NF-кB、p38丝裂原活化的蛋白激酶(MAPK)、ERKl蛋白水平与对照组相比,差别有统计学意义(P<0.05);吡格列酮明显增加PPAR-γ蛋白水平,降低NF-кB、p38 MAPK、ERKl的表达水平;非诺贝特能使PPAR-α.表达水平明显升高,也能够降低NF-кB、p38MAPK的水平.结论 非诺贝特和吡格列酮在一定程度上可以纠正胰岛功能的异常和细胞内信号转导的紊乱,保护胰岛细胞.     

顽固性高血压伴代谢综合征36例降压疗效观察

目的探讨顽固性高血压伴代谢综合征的治疗效果。方法将每日口服缬沙坦胶囊80mg,吲达帕胺片2.5mg和硝苯地平控释片30mg治疗8周血压仍未达控制目标的顽固性高血压伴代谢综合征36例患者随机分为3组,各12例,每日A组加服吡格列酮片15mg和非诺贝特缓释片250mg,B组单加吡格列酮片15mg,C组单加非诺贝特缓释片250mg,加强治疗8周。治疗前后检测患者的血压、血清甘油三酯、空腹血糖水平及腰围的变化。结果加强治疗8周后,3组的血压、血清甘油三酯及空腹血糖水平较治疗前显著下降(P<0.01);A组的血压目标控制率的升高、空腹血糖和甘油三酯水平的下降比B组或C组有显著差异(P<0.01),但各组的腰围无显著变化(P>0.05)。结论吡格列酮联合非诺贝特能显著的改善缬沙坦、硝苯地平控释片和吲达帕胺对顽固性高血压伴代谢综合征的血压水平控制。     

过氧化物酶体增殖物激活型受体α、γ配体对血管紧张素Ⅱ诱导心脏成纤维细胞增殖的抑制作用

目的探讨过氧化物酶体增殖物激活型受体(PPARs)配体对血管紧张素Ⅱ(AngⅡ)诱导心脏成纤维细胞(CFs)增殖的影响及其机制.方法体外传代培养乳鼠CFs,分别以非诺贝特(PPARα配体)和(或)吡格列酮(PPARγ配体)预处理24 h后,加用AngⅡ刺激诱导CFs增殖.应用流式细胞仪分析细胞周期,以MTT比色法测定心肌细胞活力,反映细胞增殖及胶原合成.结果与对照组比较,非诺贝特、吡格列酮均降低AngⅡ诱导的CFs的S期细胞比率和增殖指数,抑制AngⅡ引起细胞活力改变和增殖(P＜0.01).相对单独用药组,2药合用组的上述指标差异无统计学意义(P＞0.05).结论PPARs信号通路激活能有效抑制AngⅡ诱导的CFs增殖,预防心肌纤维化.PPARα、γ配体合用未见明显叠加效应.     

Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10?mg/kg per day)+Feno (25?mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ～50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (～45%) and bone mineral density (BMD; ～60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.     

视黄醇结合蛋白4与糖尿病大血管病变的关系及吡格列酮的干预作用

目的研究视黄醇结合蛋白4(RBP4)、单核细胞趋化蛋白-1(MCP-1)在糖尿病动脉粥样硬化大鼠血清中的表达及吡格列酮的干预作用。方法 75只Wistar大鼠随机选取60只以高脂、高糖及链脲佐菌素诱导制成糖尿病模型,造模成功56只大鼠随机分为糖尿病组(38只)和药物干预组(干预组,18只,吡格列酮20 mg·kg~(-1)·d~(-1)灌胃)。另15只大鼠以普通饲料喂养作为对照组。3组大鼠16周后处死,取主动脉全段行HE染色,根据动脉粥样硬化的严重程度,将糖尿病组分为单纯糖尿病组(单纯组,14只)和糖尿病合并动脉粥样硬化组(合并组,24只),测空腹血糖(FBG)、空腹胰岛素(FINS)、TC、TG、HDL-C、LDL-C及血清RBP4,MCP-1,计算动脉粥样硬化指数(AIP)及胰岛素抵抗指数(HOMA-IR)。结果糖尿病组TG、LDL-C、FBG、FINS、RBP4、MCP-1、HOMA-IR、AIP高于对照组(P<0.05),干预组除RBP4与单纯组无差异外,上述指标均较单纯组和合并组下降;RBP4与TG、LDL-C、HOMA-IR、AIP、MCP-1呈正相关,与HDL-C呈负相关。RBP4、TG是糖尿病发生大血管病变的独立危险因素。结论 RBP4是糖尿病发生大血管病变的独立危险因素;吡格列酮对糖尿病大血管病变有保护作用。     

吡格列酮对急性心肌梗死小鼠心脏血管再生及心功能的影响

目的：观察吡格列酮对心肌梗死（MI）小鼠血管再生及心功能的影响方法：结扎小鼠左冠状动脉建立小鼠MI模型,将造模成功的32只小鼠随机分成AMI组和Pio组（每组各16只）,Pio组给予吡格列酮20 mg/（kg·d）灌胃,AMI组给予等量生理盐水灌胃,另15只小鼠仅穿线不结扎为Sham组 于手术后28d检测3组小鼠心功能指标,取小鼠心肌梗死边缘处心肌组织行HE染色病理学检查,CD31染色检测心肌新生血管密度结果：治疗28 d后,Pio组生存率高于AMI组,心功能射血分数（EF）、短轴缩短率（FS）较AMI组有明显改善Pio组较AMI组纤维组织增生及炎性细胞浸润的情况减轻Pio组梗死区的微血管密度明显大于AMI组结论：吡格列酮可能有促进缺血心肌血管再生、保护缺血心肌、改善心功能的作用.     

Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study

Aim: To assess the efficacy and safety of adding alogliptin versus uptitrating pioglitazone in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone. Methods: In this randomized, double‐blind, active‐controlled, parallel‐group study, patients with type 2 diabetes and A1c ≥7.0 and ≤10.0% on metformin (≥1500 mg or maximum tolerated dose; Met) and pioglitazone 30 mg (Pio30) received alogliptin 25 mg (Alo25; n = 404) or pioglitazone 15 mg (n = 399) added to Met+Pio30 for 52 weeks. The primary endpoint was change from baseline (CFB) in A1c at weeks 26 and 52, with sequential testing for non‐inferiority of Met+Pio30+Alo25 at weeks 26 and 52 and then for superiority at week 52. Results: Met+Pio30+Alo25 showed superior glycaemic control versus Met+Pio45 at week 52 [least squares (LS) mean CFB in A1c, ?0.70 vs. ?0.29%; p < 0.001]. At week 52, Met+Pio30+Alo25 resulted in greater CFB in A1c regardless of baseline A1c (p < 0.001); higher proportions of patients achieving A1c ≤7.0 (33.2 vs. 21.3%) and ≤6.5% (8.7 vs. 4.3%; p < 0.001); greater CFB in fasting plasma glucose (FPG; LS mean CFB, ?0.8 vs. ?0.2 mmol/L; p < 0.001); and greater improvements in measures of β‐cell function (p < 0.001). Hypoglycaemia incidence was low (Met+Pio30+Alo25, 4.5%; Met+Pio45, 1.5%), mostly mild to moderate, but with two severe events in the Met+Pio30+Alo25 group. No meaningful differences in incidences of individual adverse events were observed between treatments. Conclusions: Adding alogliptin to an existing metformin–pioglitazone regimen provided superior glycaemic control and potentially improved β‐cell function versus uptitrating pioglitazone in patients with type 2 diabetes, with no clinically important differences in safety.     

Pioglitazone treatment in type 2 diabetes mellitus when combined with portion control diet modifies the metabolic syndrome

Background: Treatment with thiazolidinediones (TZDs) produces weight gain. Objective: To test whether a portion control diet could prevent weight gain during treatment with pioglitazone in patients with type 2 diabetes mellitus (T2DM). Design: This 16‐week randomized, open‐label, parallel arm study compared three groups: (i) pioglitazone plus the American Diabetes Association diet (Pio + ADA); (ii) pioglitazone plus a portion control weight loss diet (Pio + PC); (iii) metformin plus the American Diabetes Association diet (Met + ADA). All participants received the same advice about calorie reduction, lifestyle change and exercise. Methods: Fifty‐one men and women with T2DM, naive to TZDs, were randomized to a 16‐week study. Pioglitazone (Pio) was titrated to a dose of 45 mg/day and metformin (Met) to a dose of 2 g/day. Fasting blood was collected for lipids, insulin and glycosylated haemoglobin A1c (HbA1c) at baseline and 16 weeks. Results: Forty‐eight of fifty‐one randomized subjects completed the study. Patients treated with Pio + ADA gained 2.15 ± 1.09 kg (mean ± SD) compared with a weight loss of 2.59 ± 1.25 kg (p < 0.05) in the Pio + PC group, and a weight loss of 3.21 ± 0.7 kg (p < 0.05) in the Met + ADA group. Waist circumference and visceral adipose tissue decreased significantly more in the Pio + PC group than in the Pio + ADA group. High‐density lipoprotein cholesterol levels were significantly increased in the Pio + PC group compared with the Met + ADA group. Pioglitazone reduced insulin resistance (homeostasis model assessment of insulin resistance (HOMA‐IR)) more than metformin. No significant differences between groups were seen for glucose, insulin, HbA1c or low‐density lipoprotein cholesterol levels. Conclusions: Pio + PC, prevented weight gain, reduced waist circumference and visceral fat compared with Pio + ADA diet.     

高同型半胱氨酸对高血压大鼠血管平滑肌细胞GRP78和CHOP的表达的影响与血管重构的关系

目的：观察同型半胱氨酸（Homocysteine,Hcy）对高血压大鼠内质网应激因子GRP78和CHOP表达及血管中层厚度变化,探讨Hcy对血管重构的影响。方法：采用腹主动脉缩窄术建立高血压大鼠模型,术后两周采用无创尾套法测量大鼠血压,选取24只成年雄性大鼠[平均动脉压（MAP）〉150mmHg]随机等分为2组,即对照组和蛋氨酸组,每组12只（n=12）。对照组给予普通饮食＋双蒸水灌胃,蛋氨酸组给于30g/L蛋氨酸饮食＋双蒸水灌胃;根据实验结束的时间,又将各组分为4W和8W两个亚组,各亚组6只（n=6）。用同型半胱氨酸检测仪检测血清同型半胱氨酸浓度,用颈动脉插管法测定各组大鼠的MAP,并利用图像分析软件测量血管中层的厚度;HE染色观察大鼠主动脉血管形态学变化;通过免疫组化及Western blot检测大鼠主动脉血管平滑肌细胞（VSMCs）组织中GRP78及CHOP表达水平。结果：①对照组大鼠血清Hcy浓度在正常值范围（〈10μmol／L）;蛋氨酸组大鼠血清Hcy浓度明显高于对照组（P〈0．01）。②两组大鼠MAP均显著增高,4周时两者之间差异不明显,8周时两者差异显著（P〈0．05）;③蛋氨酸组大鼠血管平滑肌中层厚度显著大于对照组（P〈0．05）;④HE染色显示,与对照组相比,蛋氨酸组大鼠主动脉VSMCs显著肥大,管壁显著增厚;⑤两组CRP78和CHOP蛋白表达量增高,与对照组相比蛋氨酸组表达更明显。结论：高同型半胱氨酸可能通过促使高血压大鼠动脉VSMCs内质网应激反应,导致CRP78及CHOP的平衡失调加剧,从而引起血管损伤加重,而发生血管重构加重。     

Inflammatory cytokines and chemokines,skeletal muscle and polycystic ovary syndrome: Effects of pioglitazone and metformin treatment

ObjectiveChronic low-grade inflammation is a common feature of insulin resistant states, including obesity and type 2 diabetes. Less is known about inflammation in Polycystic Ovary Syndrome (PCOS). Thus we evaluated the impact of PCOS on circulating cytokine levels and the effects of anti-diabetic therapies on insulin action, cytokine and chemokine levels and inflammatory signaling in skeletal muscle.MethodsTwenty subjects with PCOS and 12 healthy normal cycling (NC) subjects of similar body mass index were studied. PCOS subjects received oral placebo or pioglitazone, 45 mg/d, for 6 months. All PCOS subjects then had metformin, 2 g/day, added to their treatment. Circulating levels of cytokines, chemokines, and adiponectin, skeletal muscle markers of inflammation and phosphorylation of signaling proteins, insulin action evaluated by the hyperinsulinemic/euglycemic clamp procedure and Homeostasis Model Assessment of Insulin Resistance were measured.ResultsCirculating levels of a number of cytokines and chemokines were generally similar between PCOS and NC subjects. Levels in PCOS subjects were not altered by pioglitazone or metformin treatment, even though whole body insulin action and adiponectin levels increased with pioglitazone. In spite of the lack of change in levels of cytokines and chemokines, several markers of inflammation in skeletal muscle were improved with Pio treatment.ConclusionsPCOS may represent a state of elevated sensitivity of inflammatory cells in skeletal muscle to cytokines and chemokines, a property that could be reversed by pioglitazone treatment together with improved insulin action.     

胰岛素抵抗大鼠视黄醇结合蛋白4骨骼肌磷脂酰肌醇3激酶的表达及吡格列酮的干预作用

目的 观察胰岛素抵抗(IR)大鼠体内视黄醇结合蛋白4(RBP4)、骨骼肌磷脂酰肌醇3激酶( P13K)和晚期氧化蛋白产物(AOPP)的水平,以及给予吡格列酮干预后其活性的变化,探讨RBP4与IR的关系及其可能的机制。 方法 将SPF级雄性Wistar大鼠35只随机分为2组,正常对照组（对照组）11只,饲以普通饲料;模型组24只,饲以高糖高脂饲料。模型组造模成功后再随机分为2个亚组,IR组和IR+吡格列酮干预组（干预组）,每组12只;IR组和干预组继续饲以高糖高脂饲料,干预组大鼠同时给予吡格列酮20mg·kg 1·d-1灌胃,持续8周。第16周末处死大鼠取血检测三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)及空腹血糖(FBG)、空腹胰岛素(FINS),计算胰岛素抵抗指数(HOME-IR);酶联免疫吸附法(ELISA)检测血清RBP4水平,RT-PCR测定附睾脂肪组织RBP4表达;免疫组织化学染色检测骨骼肌PI3K水平;紫外分光光度计法测定AOPP水平;并取大鼠腹腔内肠系膜、附睾、腹膜反折处的脂肪组织称质量,计算腹部脂肪含量与体质量的比值。 结果 (1)IR组大鼠体质量16周后明显增加,TG、LDL-C、FINS以及脂体比较对照组均明显升高,而HDL-C则明显降低;吡格列酮干预后,干预组体质量、TG、LDL-C、FINS以及脂体比较IR组有明显下降,HDL-C明显升高;(2)IR组大鼠血清及附睾脂肪组织RBP4水平和血清AOPP水平明显高于对照组,干预组水平明显降低;(3)IR组大鼠骨骼肌组织PI3K表达水平明显低于对照组,吡格列酮干预其表达水平升高;(4)相关分析表明大鼠血清RBP4与FINS、脂体比、LDL-C呈正相关;与HDL-C、骨骼肌组织PI3K水平呈负相关。 结论 (1)IR大鼠RBP4、AOPP水平升高,RBP4是致IR的脂肪细胞因子,并可引起机体脂代谢紊乱及氧化应激增强;(2)RBP4降低大鼠胰岛素敏感性可能与其削弱胰岛素信号转导作用有关;(3)吡格列酮可降低IR大鼠RBP4及血清AOPP水平,增加骨骼肌PI3K表达,从而提高机体对胰岛素的敏感性。