单侧输尿管梗阻大鼠肾脏过氧化物酶体增生物激活受体-γ的表达及其意义

目的：观察不同时限单侧输尿管梗阻(UUO)模型大鼠肾皮质过氧化物菌体增生物激活受体(PPAR)γ的表达变化及其与巨噬细胞浸润的关系。方法：用免疫组化、RT-PCR以及Western blotting的方法检测UUO大鼠梗阻3天、7天、14天的PPARγ在核酸水平和蛋白质水平的表达量变化以及表达位置的改变，其与ED-1阳性巨噬细胞浸润数的关系。结果：假手术对照组PPARγ主要表达于肾脏内髓集合管，而UUO状态下肾小管上皮细胞出现PPARγ的表达。半定量分析显示UUO后3天PPARγ的表达开始有增高趋势，7天时PPARγ的mRNA和蛋白质水平达到峰值(与对照组相比分别为3．33倍和4．36倍)，而梗阻后14天其表达已开始下降。病理学和免疫组化结果显示，UUO7天时巨噬细胞浸润明显，但纤维化改变尚不显著。UUO14天时炎性细胞积聚明显，但巨噬细胞浸润数下降，出现明显的小管萎缩和间质纤维化。UUO后PPARγ的表达与巨噬细胞浸润显著相关。结论：UUO模型大鼠肾皮质中PPARγ的表达量增加，并在肾小管部位出现PPARγ的表达。PPARγ的表达与肾间质巨噬细胞浸润显著相关。     

非酒精性脂肪肝患者不宜轻易使用噻唑烷二酮类药物

Belfort等人最近发表在新英格兰医学杂志上的报告证实匹格列酮药物对非酒精性脂肪肝（NASH）有改善作用，越来越多诊断为机能紊乱的患者将接受过氧化物酶体增生物激活受体γ（PPAR-γ）促效剂治疗。由Balas等人研究发表的文章提醒我们，必须权衡其益处与这些药物风险之间的关系。[第一段]     

子宫内膜癌组织中过氧化物酶体增生物激活受体γ的表达及意义

目的观察子宫内膜癌组织中过氧化物酶体增生物激活受体γ(PPARγ)的表达,并分析其意义。方法采用免疫组化技术检测40份子宫内膜癌组织及其癌旁组织、30份正常子宫内膜组织中PPARγ的表达情况,分析其与子宫内膜癌患者临床病理特征的关系。结果 PPARγ在子宫内膜癌中的阳性表达率为67.50%,显著高于正常子宫内膜(13.33%)及癌旁组织(17.50%)(P均<0.01)。子宫内膜癌组织中PPARγ阳性表达与肿瘤组织学分级、FIGO分期有关(P均<0.05)。结论子宫内膜癌组织中PPARγ过表达;检测其表达可能对子宫内膜癌的诊断有一定价值。     

过氧化物酶体增殖物激活受体γ对糖基化终产物诱导大鼠血管平滑肌细胞增殖的作用

目的观察吡格列酮对糖基化终产物（AGEs）刺激下大鼠血管平滑肌细胞（VSMCs）增殖的作用及对过氧化物酶体增殖物激活受体γ（PPARγ）基因及蛋白表达水平的影响,探讨PPARγ在AGEs诱导VSMCs增殖中的作用。方法（1）MTY法观察不同浓度、不同时间的AGEs对VSMCs增殖的影响及吡格列酮（1．0、10、100μmol／L）与AGEs共孵育对VSMCs增殖的干预作用。（2）用半定量逆转录聚合酶链反应测定VSMCs中PPARγ mRNA的表达。（3）用Western blot法检测PPARγ的蛋白表达。结果AGEs作用导致VSMCs增殖,AGEs抑制PPARγ mRNA和蛋白表达水平,这种抑制作用随着AGEs干预的时间延长和浓度的增加而增强（P〈0．05）。PPARγ激活剂吡格列酮通过增加PPARγ的表达,抑制AGEs诱导的VSMCs增殖。结论PPARγ表达的下降可能是糖尿病易患动脉粥样硬化的重要原因之一。     

过氧化物酶体增生物激活的受体γ活化对慢性阻塞性肺疾病大鼠肺中性粒细胞趋化因子表达的影响

过氧化物酶体增生物激活的受体γ(PPAR-γ)是核受体超家族转录因子，其活化对炎症反应和免疫应答可能有负调节作用，如抑制小鼠肺脂多糖(LPS)诱导的中性粒细胞增多与某些趋化因子的表达。本组研究旨在探讨PPAR-γ激活剂罗格列酮(RGZ)对慢性阻塞性肺疾病(COPD)大鼠肺中性粒细胞趋化因子表达的影响。     

过氧化物酶体增殖物激活型受体γ激动剂改善糖尿病合并冠心病患者动脉硬化程度的研究

目的通过观察马来酸罗格列酮(罗格列酮)对2型糖尿病合并冠心病患者代谢指标(血脂、血糖、胰岛素、糖化血红蛋白)、高敏C反应蛋白(hsCRP)、动脉硬化的影响,明确过氧化物酶体增殖物激活型γ(PPAR-γ)激动剂能否改善大动脉脉搏波速度,降低动脉硬化程度,并探讨其潜在机制.方法共46例患者被随机分为两组;治疗组26例,服用罗格列酮(4 mg/d)治疗12周;对照组20例,不改变合并用药.分别在0周(基线)、12周测定血脂、血糖、胰岛素抵抗指数、hsCRP等;并应用COLIN-VP1000动脉硬化测定仪测量研究对象的脉搏波速度以评价对动脉硬化的影响.结果罗格列酮4 mg/d治疗12周后,与基线水平及对照组相比,显著降低空腹血糖、改善胰岛素抵抗;此外,治疗组的脉搏波速度也显著低于对照组[(1 438±217.3)cm/s与(1 696±184.1)cm/s,t=4.26,P＜0.01].相关性分析显示,马来酸罗格列酮治疗前后hsCRP的降低与胰岛素抵抗的改善程度相关(r=0.48,P＜0.05).结论PPAR-γ激动剂可能通过改善代谢、降低胰岛素抵抗、抗炎症等机制降低2型糖尿病合并冠心病患者的大动脉脉搏波速度,从而降低动脉硬化程度.     

Vitamin C Improves Endothelium-Dependent Vasodilation in Patients With Insulin-Dependent Diabetes Mellitus

Objectives. We sought to determine whether the antioxidant vitamin C improves endothelium-dependent vasodilation of forearm resistance vessels in patients with insulin-dependent diabetes mellitus.Background. Endothelium-dependent vasodilation is impaired in patients with diabetes mellitus. Oxidatively mediated degradation of endothelium-derived nitric oxide contributes to abnormal endothelium-dependent vasodilation in animal models of diabetes mellitus.Methods. The study group included 10 patients with insulin-dependent diabetes mellitus and 10 age-matched control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3 to 10 μg/min). Endothelium-independent vasodilation was assessed by intraarterial infusion of nitroprusside (0.3 to 10 μg/min). Forearm blood flow dose–response curves were determined for each drug infusion before and during concomitant infusion of vitamin C (24 mg/min).Results. In diabetic subjects, endothelium-dependent vasodilation was augmented by the concomitant infusion of vitamin C (p = 0.001). Endothelium-independent vasodilation was not affected by the concomitant infusion of vitamin C (p = NS). In control subjects, vitamin C infusion did not affect endothelium-dependent vasodilation (p = NS).Conclusions. Vitamin C selectively restores the impaired endothelium-dependent vasodilation in the forearm resistance vessels of patients with insulin-dependent diabetes mellitus. These findings indicate that nitric oxide degradation by oxygen-derived free radicals contributes to abnormal vascular reactivity in humans with insulin-dependent diabetes mellitus.     

Cardiovascular Risk Factors in Patients With Congenital Heart Disease

Survival of infants born with congenital heart disease (CHD) is improving tremendously and although most of them have mild lesions, others might be considered as only being palliated and undergo many medical or surgical interventions. Patients with CHD will be exposed to the same problematic of the modern lifestyle such as increased prevalence of obesity, decreased physical activities, and exposure to smoking, which leads to acquired cardiovascular disease. We specifically investigated specific cardiovascular risk factors such as: malnutrition, smoking exposure, hypertension, integrity of the coronary and systemic arteries, thromboembolism, ventricular dysfunction, inflammation, and arrhythmias. Patients with CHD are often submitted to extremes of nutrition: as infants, they often do not meet their metabolic requirements, and as they grow older, they tend to exceed them, as seen in the general population. Some heart lesions are more prone to systemic hypertension throughout life, such as coarctation of the aorta, but surprisingly other lesions are also prone to hypertension such as Ebstein anomaly, pulmonary valve stenosis, or regurgitation. Early coronary artery atherosclerosis is also a concern in these patients. Lesions typically at risk are localized in zones of increased turbulence or high pressure or having had previous surgical manipulations. Thromboembolism is also frequent and mostly associated with arrhythmias, heart failure, multiple catheterizations, and specific surgical repairs. Finally, the complexity of heart lesions or abnormal hemodynamics lead to inflammation, heart failure, or arrhythmias. These complex interactions of risk factors ultimately lead to a decreased life expectancy.     

过氧化物酶体增生物激活受体γ共激活因子1α基因G482S和+2962A/G多态性与国人高血压患病的关系

目的研究中国北方社区人群中过氧化物酶体增生物激活受体γ共激活因子-1α基因(PGC-1α)G482S和 2962A/G多态性与高血压患病的关系。方法2004年整群随机抽取1642名(男648名,女994名,年龄35～91岁)山西农民,进行心血管流行病学调查及G482S和 2962A/G多态性检测。结果调整性别、年龄、体重指数和近期服用降血压药后,G482S、 2962A/G以及2个位点的单倍型组合与收缩压、舒张压及高血压(SBP≥140 mm Hg或DBP≥90 mm Hg或近期服用降压药物)患病危险无显著相关关系(P>0.05)。进一步分析发现,与G482G携带者相比,S482S携带者患较重高血压(SBP≥160 mm Hg或DBP≥100 mm Hg)的危险比值比(OR)为0.6(95% CI:0.4～0.98),与 2962A/A携带者相比, 2962G/G携带者OR值为1.9(95% CI:1.2～3.0),与S482SII 2962A/A单倍型组合携带者相比,G482GII 2962G/G携带者值OR为2.6(95% CI:1.5～4.4)。结论PGC-1α基因G482S和 2962A/G多态性与国人较重高血压患病存在显著关系。     

运动对高脂血症大鼠骨骼肌过氧化体增殖物激活型受体γ辅激活因子1表达的影响

目的通过研究高脂血症大鼠运动后骨骼肌过氧化体增殖物激活型受体γ辅激活因子1的变化，探讨过氧化体增殖物激活型受体γ辅激活因子1在运动改善大鼠能量代谢中的作用。方法将26只大鼠分为3组，正常对照组9只，高脂膳食组（高脂组）9只，高脂膳食＋60min运动组（运动组）8只。测定各组骨骼肌过氧化体增殖物激活型受体γ辅激活因子1基因和蛋白表达的变化。结果高脂组甘油三酯、总胆固醇和低密度脂蛋白胆固醇较对照组显著升高（P〈0．05）；运动组甘油三酯、总胆固醇和低密度脂蛋白胆固醇较高脂组显著降低（P〈0．05），高密度脂蛋白胆固醇较高脂组显著升高（P〈0．05）。与对照组比较，运动组大鼠骨骼肌过氧化体增殖物激活型受体γ辅激活因子1mRNA表达显著增高（P〈0．01）；与高脂组大鼠比较，运动组大鼠骨骼肌过氧化体增殖物激活型受体γ辅激活因子1mRNA表达显著增高（P〈0．05）。运动组骨骼肌过氧化体增殖物激活型受体γ辅激活因子1蛋白表达较对照组增加了2．14倍（P〈0．05），较高脂组增加了2．02倍（P〈0．05）。结论运动能够通过过氧化体增殖物激活型受体γ辅激活因子1改善骨骼肌的能量代谢，从而改善机体的脂质代谢，防止糖代谢异常和动脉粥样硬化的发生。     

Association of Hyperuricemia With Conventional Cardiovascular Risk Factors in Elderly Patients

The relationship between serum uric acid (UA) and cardiovascular risk profile was investigated in 557 outpatients (415 women) aged 60 years and older. Patients were grouped according to a UA cutoff level of 5.5 mg/dL. Prevalence of obesity, hypertension, and impaired glucose metabolism was increased in women with higher UA, who had higher body mass index (37.7±6.9 vs 33.1±5.9 kg/m², P<.001), waist circumference, and serum glucose and triglyceride concentrations than women with lower UA levels. Conversely, men with higher UA levels showed lower high‐density lipoprotein cholesterol and higher left ventricular mass than men with lower UA levels. Estimated glomerular filtration rate was reduced in patients with high UA levels of both sexes (65±17 vs 72±16 mL/min/1.73 m², P<.001, for women; 70±16 vs 76±15 mL/min/1.73 m², P<.03, for men). Grouping patients by sex‐specific median UA concentrations produced similar results. These data indicate that, even in the elderly, UA clusters in a sex‐specific fashion with features of metabolic syndrome and signs of target organ damage.     

高血压患者发生心血管事件危险因素的探讨

目的:探讨心血管危险因素对高血压患者10年间发生心血管事件的影响。方法:将随访到的380例住院高血压患者,根据患者是否在10年间新发主要心血管事件分为两组:事件组(n=159,至少新发主要心血管事件中的一项),无事件组(n=221,没有新发任何一项主要心血管事件),分析两组高血压患者的基线危险因素的特征及其对新发心血管事件的的影响。结果:159例新发心血管事件中发生率由高到低依次为脑血管病(23%)、冠心病(22%)、心脑血管病死亡(17%)、肾功能受损(15%)、心功能不全(12%)、糖尿病(11%)。事件组高血压患者合并基线危险因素的平均个数显著高于无事件组(2.17±1.05比1.36±0.97,P0.001)。事件组高血压患者高龄、血脂异常、糖尿病、吸烟、早发心血管病家族史比例显著高于无事件组(均P0.05)。经多因素Logistic回归,并调整年龄、性别、血压水平、高血压病程、脉压影响后,吸烟、糖尿病、血脂异常与新发心血管事件呈正相关,比值比(OR)分别为2.667(95%CI:1.449~4.478)、1.854(95%CI:1.027~3.346)、1.657(95%CI:1.028~2.672)。调整混杂因素后,每增加一个危险因素,新发心血管事件危险增加46%。结论:吸烟和糖尿病是高血压患者发生新发心血管事件的主要可改变危险因素。