高脂饮食致ApoE-/-小鼠动脉粥样硬化及主动脉瓣钙化的实验研究

目的 探讨高脂饮食致ApoE-/-小鼠动脉粥样硬化及主动脉瓣钙化模型的病理特点.方法 10只8周龄C57BL/6J小鼠纳入正常组,20只8周龄ApoE-/-小鼠随机分为对照组和模型组.正常组和对照组给予普通饮食,模型组给予高脂饮食,连续喂养24周.各组小鼠行超声心动图检测.实验结束处死小鼠后检测血清中总胆固醇(tota...     

晚期糖基化终产物受体阻断剂FPS-ZM1减缓ApoE-/-小鼠动脉粥样硬化进展的作用

目的 研究晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)阻断剂FPS-ZM1对ApoE-/-小鼠高脂喂养后动脉粥样硬化(atherosclerosis,AS)进展的干预作用.方法 ApoE-/-小鼠随机分成对照组(普通喂养),AS模型组(高脂喂...     

高脂喂养对ApoE基因敲除小鼠胆固醇代谢相关基因表达的影响

建立高脂诱导载脂蛋白E基因敲除(ApoE-/-)小鼠胰岛素抵抗模型,探讨其对胆固醇代谢相关基因表达的影响.结果 显示高脂喂养组ApoE-/-小鼠空腹血糖、游离脂防酸、总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和空腹血浆胰岛素水平明显高于对照组(均P＜0.01);肝组织中INSIG2和SCAP mRNA明显升高(P＜0.05或P＜0.01),肝INSIG2蛋白水平也明显增高(P＜0.05);而SREBP1 mRNA表达明显降低(P＜0.05).这些改变可能在该小鼠模型胆固醇代谢紊乱和胰岛素抵抗的发生中具有一定的作用.

Abstract：

To investigate the effect on gene expression related cholesterol metabolism in ApoE-/- mice with high-fat-induced insulin resistance(IR). In high-fat fed mice, FBG, FFA, TC, TG, LDL-C, HDL-C, and fasting plasma insulin were significantly higher than those of controls(P＜0.01). The INSIG2 and SCAP mRNA expressions in liver were significantly increased in high-fat fed mice compared with controls(P＜0. 05 or P＜0.01), and INSIG2 protein levels also increased(P＜0. 05). But SREBP1 mRNA expression in liver of high-fat fed mice was significantly reduced(P＜0. 05). These changes might contribute to IR and disorder of cholesterol metabolism in high-fat fed ApoE-/- mice.     

17β-雌二醇对ApoE-/-鼠Teff/Treg细胞平衡和氧化应激的影响及与动脉粥样硬化的关系

目的探讨不同时间给予17β-雌二醇(E2)替代治疗对apo E-/-雌鼠动脉粥样硬化(As)病变内效应性T细胞(Teff)和调节性T细胞(Treg)平衡和氧化应激的影响及其与As的关系。方法 5周龄apo E-/-鼠摘除卵巢后用高脂餐喂养,随机分为早期、延迟及持续治疗组,给予E2皮下注射(5μg/天)8周或16周,检测主动脉根部As病变大小、组成改变以及硫氧还蛋白TRX1的表达,并检测As病变内Th1细胞的细胞因子IFN-γ、Treg细胞的转录因子Foxp3和TRX1 m RNA的表达。结果 (1)和对照组相比,早期E2治疗使apo E-/-鼠脂质条纹的面积显著减少(8.82%±0.98%vs.19.3%±1.26%in controls,P0.01);而延迟E2治疗纤维脂质斑块的面积明显增加(30.7%±0.74%vs.25.1%±0.94%in controls,P0.05);持续E2治疗纤维脂质斑块的面积亦明显降低(22.48%±0.92%vs.25.63%±1.04%in controls,P0.05);(2)延迟E2治疗斑块内胶原和平滑肌细胞含量明显减少,而巨噬细胞数量显著增加;持续E2治疗斑块内胶原和平滑肌细胞含量明显增加,而巨噬细胞数量明显减少;(3)早期及持续E2治疗As病变内代表促炎作用的IFN-γm RNA的表达明显降低,而延迟E2治疗斑块内IFN-γm RNA的表达明显增加;(4)早期及持续E2治疗AS病变内代表抑炎作用的Foxp3 m RNA的表达明显增加,而延迟E2治疗斑块内Foxp3 m RNA的表达明显降低;(5)早期及持续E2治疗,apo E-/-鼠血清过氧化脂质(LPO)的含量明显减少,而延迟E2治疗血清LPO含量明显增加;(6)早期及持续E2治疗As病变内TRX1 m RNA及蛋白水平的表达明显降低;而延迟E2治疗斑块内TRX1 m RNA及蛋白水平的表达却明显增加。结论 apo E-/-鼠摘除卵巢后,早期E2替代治疗可抑制As病变的形成,而缺乏雌激素一定时间后,再给予E2治疗却加速了As病变的进展并使斑块趋于不稳定,其机制与调节Teff/Treg细胞平衡以及对氧化应激的影响有关。     

阿托伐他汀对ApoE-/-小鼠主动脉粥样硬化和钙化的影响

目的 探讨阿托伐他汀对ApoE-/-小鼠主动脉粥样硬化及钙化的影响.方法 12只6周龄ApoE-/-小鼠,予以高脂饮食喂养8周后,随机分为高脂组(n=6)和高脂加阿托伐他汀组(n=6),连续灌胃干预8周,于22周龄时处死,测定血清血脂、IL-6及A-SAA水平;HE染色观察主动脉粥样硬化及Von Kossa染色观察主动脉钙化;免疫组织化学染色法分析比较两组VCAM-1、MCP-1、BMP-2表达;阿托伐他汀干预人主动脉内皮细胞,测定细胞内钙含量及AKP活力,并用Western blot法测定BMP-2蛋白表达水平.结果 高脂加阿托伐他汀组ApoE-/-小鼠血清TG、TC及LDLC水平显著低于高脂组(P＜0.05);且血清IL-6及A-SAA水平较高脂组亦显著降低(P＜0.05);高脂组ApoE-/-小鼠主动脉内膜出现典型粥样硬化斑块,管腔面积缩小,高脂加阿托伐他汀组的病变程度较轻;但高脂加阿托伐他汀组ApoE-/-小鼠主动脉内膜钙盐沉积量显著高于高脂组(P＜0.05).高脂加阿托伐他汀组ApoE-/-小鼠主动脉血管壁VCAM-1、MCP-1的表达显著低于高脂组(P＜0.01),而BMP-2的表达显著高于高脂组(P＜0.01).阿托伐他汀处理人主动脉内皮细胞后,高剂量阿托伐他汀可使细胞内BMP-2蛋白表达水平显著高于对照组(P＜0.05),并使钙含量及AKP活力比低剂量组和对照组显著增加(P＜0.01,P＜0.05).结论 阿托伐他汀可降低高脂喂养的ApoE一小鼠血清TG、TC、LDL-C及IL-6、A-SAA水平,减少主动脉血管壁VCAM-1、MCP-1的表达,同时减轻主动脉粥样硬化的病变程度;但增加ApoE-/-小鼠主动脉内膜BMP-2表达,促进钙盐沉积,增加人主动脉内皮细胞BMP-2蛋白表达、钙含量及碱性磷酸酶活力,加重主动脉内膜的钙化.     

罗格列酮改善高脂饲养大鼠胰岛素抵抗机制的研究

目的探讨罗格列酮改善高脂饮食大鼠胰岛素敏感性的机制。方法SD大鼠随机分为正常对照组、高脂饮食对照组、高脂饮食罗格列酮治疗组，治疗组灌服罗格列酮。采用葡萄糖-胰岛素耐量实验测量大鼠胰岛素敏感性K值，并观察不同部位脂肪组织重量的变化及其与胰岛素敏感性K值的关系。采用RT-PCR法检测大鼠腹腔脂肪组织中TNF-α、leptin、PPAR-γ表达的变化情况；应用TUNNEL法观察腹腔脂肪细胞凋亡的变化。结果7周后，高脂饮食罗格列酮治疗组大鼠与高脂对照组相比，胰岛素抵抗明显改善，K值升高；腹腔脂肪重量减少，皮下脂肪重量相对增加；腹腔脂肪组织TNF-α、leptin表达量明显下降，PPAR-γ表达未见改变；大鼠腹腔脂肪细胞凋亡增加。但与正常对照组相比未见明显差异。结论胰岛素抵抗与腹腔脂肪组织关系密切；罗格列酮改善高脂饮食大鼠胰岛素敏感性的机制可能是通过调控脂肪细胞凋亡，影响脂肪细胞的分布，减少引起胰岛素抵抗的细胞因子的表达，从而改善胰岛素抵抗。     

吡格列酮联合二甲双胍对2型糖尿病患者胰岛素抵抗及脂肪细胞因子水平的影响

目的观察吡格列酮联合二甲双胍治疗2型糖尿病(T2DM)的疗效,探讨治疗对患者胰岛素抵抗及脂肪细胞因子水平的影响。方法将我院收治的T2DM患者72例随机分为观察组和对照组,每组36例。对照组给予口服二甲双胍治疗,观察组给予二甲双胍联合盐酸吡格列酮治疗。观察两组患者治疗前后空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(F-INS)和胰岛素抵抗指数(Homa IR)。并应用酶联免疫吸附法(ELISA)检验两组治疗前后血浆瘦素和脂联素水平。结果治疗后两组患者FPG、2 h PBG、HbA1c和Homa IR均显著降低(均P<0.05);治疗后研究组2 h PBG、HbA1c和Homa IR显著低于对照组(均P<0.05);治疗前两组瘦素和脂联素比较无统计学差异(均P>0.05),治疗结束后两组患者血清瘦素均显著降低,血清脂联素显著升高(均P<0.05),研究组血清瘦素显著低于对照组,血清脂联素显著高于对照组(P<0.05)。结论吡格列酮联合二甲双胍治疗可以有效调节T2DM患者瘦素和脂联素水平,进一步改善患者胰岛素抵抗。     

在长期高脂喂养大鼠阻断肾素血管紧张素系统对内脂素基因表达的影响

内脂素（visfatin）是新近发现的一种脂肪因子，具有类似胰岛素的作用。本研究显示，长期高脂喂养大鼠内脂素的表达与肥胖和胰岛素抵抗相平行。阻断肾素血管紧张素系统后，内脂素表达降低，胰岛素抵抗现象改善。内脂素可能在胰岛素抵抗的发生中起重要作用。     

脂代谢紊乱和脂肪细胞因子与胰岛素抵抗

糖和脂代谢异常同属于2型糖尿病的原发病理生理事件，也是胰岛素抵抗（IR）发生和发展的主要特征。游离脂肪酸的异常在IR的形成中具有至关重要的作用，而一些具有活跃的代谢作用及复杂生理功能的脂肪细胞因子与糖、脂代谢及IR也具有双向的调节作用。     

高脂诱导胰岛素抵抗ApoE基因敲除小鼠糖脂代谢的变化

目的建立高脂诱导ApoE基因敲除（ApoE^-/-）小鼠胰岛素抵抗（IR）模型,并探讨其糖脂代谢的变化。方法高脂喂养ApoE叫小鼠16周建立IR模型,采用3-^3H葡萄糖为示踪剂的扩展高胰岛素钳夹技术评价其胰岛素敏感性和糖脂代谢变化。结果普通饲料喂养ApoE^-/-小鼠（NF组）血浆FFA、TC、TG、LDL-C、HDL-C和Ins明显高于C57BL／6J小鼠对照（NC）组（P〈0．01和P〈0．05）,而高脂喂养ApoE叫小鼠（HF组）上述指标又明显高于NF组（P均〈0．01）,并且FBG也明显高于NF和NC组（P均〈0．01）。钳夹稳态时,HF组Ins明显高于NF和NC组（P均〈0．01）,FFA、TC、TG虽被抑制,但仍明显高于NF和NC组（P均〈0．01）;HF组葡萄糖输注率明显低于NF和NC组（P均〈0．01）。在钳夹结束时,HF组葡萄糖清除率明显低于NF和NC组（P均〈0．01）,而肝糖输出率则明显高于NF和NC组（P均〈0．01）,仅被抑制51％。结论ApoE^-/-小鼠存在糖脂代谢紊乱和IR的遗传特征,长期高脂饲养后更为明显。     

Basal lipolysis, not the degree of insulin resistance, differentiates large from small isolated adipocytes in high-fat fed mice

Aims/hypothesis  Adipocytes in obesity are characterised by increased cell size and insulin resistance compared with adipocytes isolated from lean patients. However, it is not clear at present whether hypertrophy actually does drive adipocyte insulin resistance. Thus, the aim of the present study was to metabolically characterise small and large adipocytes isolated from epididymal fat pads of mice fed a high-fat diet (HFD). Methods  C57BL/6J mice were fed normal chow or HFD for 8 weeks. Adipocytes from epididymal fat pads were isolated by collagenase digestion and, in HFD-fed mice, separated into two fractions according to their size by filtration through a nylon mesh. Viability was assessed by lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium assays. Basal and insulin-stimulated d-[U-¹⁴C]glucose incorporation and lipolysis were measured. Protein levels and mRNA expression were determined by western blot and real-time RT-PCR, respectively. Results  Insulin-stimulated D-[U-¹⁴C]glucose incorporation into adipocytes isolated from HFD-fed mice was reduced by 50% compared with adipocytes from chow-fed mice. However, it was similar between small (average diameter 60.9 ± 3.1 μm) and large (average diameter 83.0 ± 6.6 μm) adipocytes. Similarly, insulin-stimulated phosphorylation of protein kinase B and AS160 were reduced to the same extent in small and large adipocytes isolated from HFD-mice. In addition, insulin failed to inhibit lipolysis in both adipocyte fractions, whereas it decreased lipolysis by 30% in adipocytes of chow-fed mice. In contrast, large and small adipocytes differed in basal lipolysis rate, which was twofold higher in the larger cells. The latter finding was associated with higher mRNA expression levels of Atgl (also known as Pnpla2) and Hsl (also known as Lipe) in larger adipocytes. Viability was not different between small and large adipocytes. Conclusions/interpretation  Rate of basal lipolysis but not insulin responsiveness is different between small and large adipocytes isolated from epididymal fat pads of HFD-fed mice.     

血栓素受体拮抗剂S18 886对ApoE-/-小鼠动脉粥样硬化的影响

目的了解血栓素受体拮抗剂S18886对ApeE-/-小鼠颈总动脉粥样硬化斑块炎细胞浸润和形态学的影响。方法制作不破坏内弹力板的环包颈总脉模型,分别每天灌喂S188865mg/kg·b.w.、氯吡格雷25mg/kg·b.w.和空白水6周。结果应用S18886药物小鼠的右颈总动脉内膜损伤面积明显被抑制,内膜/中膜比值小于对照组和氯吡格雷组(P<0.05);内膜/总血管壁面积比值也明显低于对照组和氯吡格雷组(P<0.05);S18886组小鼠斑块部位细胞间粘连分子-1(ICAM-1)水平和巨噬细胞的浸润明显降低;对照组动脉斑块内的α-平滑肌肌动蛋白显著减低,S18886和氯吡格雷组斑块内的α-平滑肌肌动蛋白明显减低。结论血栓素受体拮抗剂S18886通过减低ICAM-1,抑制斑块部位的炎细胞浸润,回缩并稳定动脉粥样硬化斑块。     

The association between the triglyceride to high-density lipoprotein cholesterol ratio with insulin resistance (HOMA-IR) in the general Korean population: based on the National Health and Nutrition Examination Survey in 2007-2009

Aim

To investigate circulating visfatin and vaspin levels in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs) who frequently have higher value of HOMA-IR and beta cell dysfunction.

Methods

Serum visfatin and vaspin concentrations were measured in 179 Iranian subjects (90 normoglycemic FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods.

Result

Serum visfatin levels were significantly lower in the FDRs when compared to the controls (1.71 ± 0.93 ng/ml versus 2.69 ± 2.02 ng/ml, p = 0.0001). However, no significant difference was found in serum vaspin concentrations between the FDRs and the controls (0.452 ± 0.254 ng/ml versus 0.409 ± 0.275 ng/ml, p > 0.05). In multiple logistic regression analysis, the FDRs showed a significant association with lower visfatin levels after adjustments for age, sex, Body Mass Index, systolic and diastolic blood pressures, lipid profile, blood glucose levels and HOMA-IR [odds ratios (OR) = 1.71, 95% confidence interval (1.30-2.25); p < 0.0001].

Conclusion

The FDRs showed a significant association with lower visfatin levels. The observed lower circulating visfatin levels in FDRs may suggest a pathophysiological role for visfatin in beta cell dysfunction in this group.     

Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet

Aim/hypothesis Hyperinsulinaemia maintains euglycaemia in insulin-resistant states. The precise cellular mechanisms by which the beta cells adapt are still unresolved. A peripherally derived cue, such as increased circulating fatty acids, may instruct the beta cell to initiate an adaptive programme to maintain glucose homeostasis. When this fails, type 2 diabetes ensues. Because mitochondria play a key role in beta cell pathophysiology, we tested the hypothesis that mitochondrial metabolism is critical for beta cell adaptation to insulin resistance. Methods C57BL/6J mice were given high-fat (HF) diet for 12 weeks. We then analysed islet hormone secretion, metabolism in vivo and in vitro, and beta cell morphology. Results HF diet resulted in insulin resistance and glucose intolerance but not frank diabetes. Basal insulin secretion was elevated in isolated islets from HF mice with almost no additional response provoked by high glucose. In contrast, a strong secretory response was seen when islets from HF mice were stimulated with fuels that require mitochondrial metabolism, such as glutamate, glutamine, alpha-ketoisocaproic acid and succinate. Moreover, while glucose oxidation was impaired in islets from HF mice, oxidation of glutamine and palmitate was enhanced. Ultrastructural analysis of islets in HF mice revealed an accumulation of lipid droplets in beta cells and a twofold increase in mitochondrial area. Conclusions/interpretation We propose that beta cells exposed to increased lipid flux in insulin resistance respond by increasing mitochondrial volume. This expansion is associated with enhanced mitochondrial metabolism as a means of beta cell compensation. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.     

阻断肾素-血管紧张素系统对长期高脂喂养大鼠肝脂肪变性的影响

目的 观察长期高脂喂养诱导胰岛素抵抗状态大鼠肝脏脂肪变性与肝内血管紧张素原(AGT)、解偶联蛋白2(UCP-2)和转化生长因子β1(TGFβ1)表达的关系,并通过阻断肾素-血管紧张素系统(RAS)观察是否改善肝脂肪变性,探讨其作用机制.方法 40只大鼠分正常对照组、高脂组、血管紧张素转换酶抑制剂(ACEI)干预高脂组、血管紧张素Ⅱ受体阻滞剂(ARB)干预高脂组.正常血糖高胰岛素钳夹试验评价胰岛素敏感性,免疫组化和RT-PCR检测肝脏内AGT、UCP-2和TGFβ1蛋白及mRNA的表达,并检测血清脂质水平和肝内脂肪含量.结果 正常对照组、高脂组、ACEI干预高脂组、ARB干预高脂组稳态第2小时葡萄糖输注率分别为(11.22±1.45)、(6.22±1.02)、(8.08±1.13)、(8.16±1.26)mg·kg-1·min-1.高脂组血清学指标和肝内脂肪含量均高于正常对照组(P＜0.05),ACEI干预高脂组、ARB干预高脂组与高脂组比较,肝内脂肪含量降低(P＜0.01),脂肪变和纤维化减轻,肝内UCP-2和TGFβ1表达减少(P＜0.05).结论 阻断RAS可改善胰岛素抵抗,并可能通过下调肝内UCP-2和TGFβ1的表达,对长期高脂喂养大鼠肝脏有保护作用.     

Roles of FOXP3 in experimental atherosclerosis of ApoE-knockout mice

Background Subtypes of T cells,called regulatory T cells(Treg cell),play a critical role in limiting autoimmune processes and inflammatory responses,The aim of this study was to explore functional roles of FOXP3 in the manifestation of atherosclerosis in Apolipoprotein E deficient(ApoE)-/-mice.Methods Lentivirus-mediated(siRNA) was used to knock down FOXP3 and FOXP3high+CD4+ CD25+ T cells adoptive transfer assays in high fat diet ApoE-/-mice were done.The resulting atherosclerotic lesions were assessed by d...     

长期高脂饮食对C57BL/6小鼠骨骼肌基因表达谱的影响

目的 运用基因芯片技术研究长期高脂饮食对C57BL/6小鼠骨骼肌基因表达谱的影响,探究长期高脂饮食导致小鼠肥胖、胰岛素抵抗(IR)和2型糖尿病(T2DM)的分子机制.方法 20只雄性4周龄C57 BL/6小鼠随机分为正常饮食组和高脂饮食组,各10只,分别饲以基础和高脂饲料.16周后,称量各组小鼠体重;测定血糖、空腹血清胰岛素(FINs)、高密度脂蛋白(HDL)、甘油三酯(TG)、总胆固醇(TC)和游离脂肪酸(FFAs)水平;随后,每组随机选取4只小鼠处死,分离股四头肌,提取总RNA进行基因芯片分析.结果 高脂饮食组与正常饮食组相比,体重显著增加;FINs水平显著升高;HDL水平无显著性差异,而TC、TG和FFA水平均显著升高.采用基因芯片相关统计软件分析数据,结果发现正常饮食组与高脂饮食组相比,骨骼肌共出现590个差异表达基因.其中表达上调基因有321个,表达下调基因有269个.结论长期高脂饮食可以引起C57BL/6小鼠骨骼肌基因谱发生显著变化.     

胰腺星状细胞活化在高脂饲养大鼠胰岛纤维化形成中的作用

探讨胰腺星状细胞(PSC)活化在高脂饲养大鼠胰岛纤维化发生中的作用.高脂饲养20周的大鼠葡萄糖输注率(GIR)以及葡萄糖刺激的胰岛素分泌都明显低于对照组(P<0.01);高脂组空腹血糖、胰岛素、游离脂肪酸以及基础胰高血糖素的分泌水平显著高于对照组(P<0.05或P<0.01),高脂组胰岛纤维化,胰岛内星状细胞活化并特异性表达α-平滑肌肌动蛋白(α-SMA),提示PSC活化、增生、迁移可能是胰岛素抵抗大鼠胰岛纤维化发生的关键环节.     

吡格列酮对胰岛素抵抗大鼠血浆同型半胱氨酸水平的影响

目的　研究吡格列酮对高脂饮食诱导的胰岛素抵抗大鼠血浆同型半胱氨酸 (Hcy)水平的影响。方法　将 2 4只Wistar大鼠随机分为 3组 :对照组给予普通饲料喂养 ;高脂组喂高脂饲料诱导胰岛素抵抗动物模型 ;盐酸吡格列酮组在喂饲高脂饲料的同时 ,灌胃给盐酸吡格列酮 10mg·kg-1·d-1。各组喂食 11周时 ,分别做空腹血糖、葡萄糖耐量试验和胰岛素耐量试验后处死动物。测定血糖和胰岛素水平 ,用HOMA模型公式计算胰岛素抵抗指数 (HOMAIR)。喂食 11周后测定血浆Hcy水平。结果　试验后 3组间体重变化、空腹胰岛素、空腹血糖、HOMAIR均有显著差异 (P <0 0 5 )。其中吡格列酮组空腹胰岛素、空腹血糖、HOMAIR均显著低于高脂组 (P <0 0 1)。试验后 3组间血浆Hcy也有显著差异 ,高脂组 (35 7± 14 1) μmol/L高于对照组 (9 95± 2 4 0 ) μmol/L和吡格列酮组 (8 8± 1 39) μmol/L。相关分析显示血糖曲线下面积、空腹胰岛素、空腹血糖、HOMAIR、内脏脂肪含量均与血浆Hcy水平显著相关 (P <0 0 5 )。进一步多元逐步回归分析显示仅空腹血糖 (r =0 5 0 4 ,P =0 0 31)和HOMAIR与血浆Hcy相关 (r=0 30 2 ,P =0 0 4 6 )。结论　高脂诱导的胰岛素抵抗与大鼠血浆Hcy水平升高有关 ,吡格列酮可能通过减轻胰岛素抵抗降低血浆H