不同类型氧化型脂蛋白对血管内皮细胞、单核细胞NFκB和PPARs的作用

目的：探讨不同类型氧化型脂蛋白作用后内皮细胞、单核细胞NFkB、IL-6表达的差异，细胞核转录因子PPARα、PPARγ、NFκB活化程度的不同。方法：超速密度梯度离心分离人血清脂蛋白，体外Cu^ 2介导氧化；人脐静脉内皮细胞的原代培养以及THP-1细胞株培养：免疫组织化学、胞浆抗原FITC标记流式细胞仪法检测不同类型氧化型脂蛋白对内皮细胞、单核细胞NFκB表达的影响，ELISA法检测上清液IL-6的表达：氧化型脂蛋白对PPARα、PPARγ、NFκB活化后，核移位率的比较。结果：Lp(a)、LDL、VLDL及HDL在相同氧化条件下，对内皮细胞、单核细胞NFκB的“核移位”作用及IL-6的表达均有差异，oxLp(a)作用最强ooxLp(a)和oxLDL对内皮细胞、单核细胞NFκB的活化程度大于PPARα和PPARγ，随作用时间而增强。结论：不同类型的氧化型脂蛋白对细胞核转录因子、炎性因子的激活强度各异。氧化型脂蛋白对核转录因子PPARα、PPARγ、NFκB的活化程度不一致。     

Cardiac metabolism,inflammation, and peroxisome proliferator-activated receptors modulated by 1,25-dihydroxyvitamin D3 in diabetic rats

Background

High free fatty acid with reduced glucose utilization in diabetes mellitus (DM) impairs cardiac function. Peroxisome proliferator-activated receptors (PPARs) modulate myocardial lipid and glucose homeostasis. The active 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) regulates oxidative stress and inflammation, which may play a key role in the modulation of PPARs. The aim of this study was to investigate whether 1,25(OH)₂D₃ can modulate the cardiac PPARs and fatty acid metabolism.

Methods

Electrocardiogram, echocardiogram, and Western blot analysis were used to evaluate cardiac fatty acid metabolism, inflammation, and PPAR isoform expression in Wistar-Kyoto (WKY) rats, DM rats, and DM rats treated with 1,25(OH)₂D₃.

Results

Compared to healthy rats, DM and 1,25(OH)₂D₃-treated DM rats had lower body weight. DM rats had larger left ventricular end-diastolic diameter, and longer QT interval than healthy or 1,25(OH)₂D₃-treated DM rats. Moreover, compared to healthy or 1,25(OH)₂D₃-treated DM rats, DM rats had fewer cardiac PPAR-α and PPAR-δ protein expressions, but had increased cardiac PPAR-γ protein levels, tumor necrosis factor-α, interleukin-6, 5′ adenosine monophosphate-activated protein kinaseα2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase 1, PPAR-γ coactivator 1-α, cluster of differentiation 36, and diacylglycerol acyltransferase 2 protein expressions.

Conclusions

1,25(OH)₂D₃ significantly changed the cardiac function and fatty acid regulations in DM hearts, which may be caused by its regulations on cardiac PPARs and proinflammatory cytokines.     

PPAR-γ配体对绒癌细胞系JEG-3体外增殖、分泌和侵袭能力的影响

目的 观察PPAR-γ配体吡格列酮(PGZ)调节绒癌细胞系JEG-3的增殖、分泌hCG和体外侵袭、转移能力.方法 用MTT法和IEMA测定细胞的增殖和分泌hCG.Matrigel侵袭模型分析细胞的迁徙和侵袭能力.结果 小剂量PGZ对JEG-3有增殖抑制作用,随PGZ浓度的增加,JEG-3透过Matrigel膜的细胞数明显减少(P＜0.01).结论 PGZ明显抑制JEG-3肿瘤细胞的生长和侵袭能力,提示PPAR-γ途径可能是妊娠滋养细胞肿瘤治疗的新方向.     

Glycine regulates inflammatory markers modifying the energetic balance through PPAR and UCP-2

Obesity is widely recognized as cause of metabolic syndrome and cardiovascular disease. It is provoked by imbalance between the spending and consumption of energy associated with a chronic inflammatory condition due to excessive storage of fat tissue. Obese patients have an impaired inflammatory profile that contributes to the development of vascular complications, with fat tissue being partially responsible for controlling both processes: energy balance (through PPAR) and inflammatory condition (through inflammatory markers). White adipose tissue produces cytokines (IL-6, TNF-α, resistin, adiponectin, etc.) and participates in a broad spectrum of processes. Recently, glycine has been reported to have anti-inflammatory properties which reduce TNF-α and IL-6 levels and increase adiponectin in 3T3-L1 adipocytes and in fat tissue of obese mice. In this study, the possible regulatory role of glycine on some factors involved in storage and energy burning (PPAR-γ, PPAR-α, PPAR-δ and UCP-2) was analyzed in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Glycine clearly increased fat tissue PPAR-γ expression in lean but not in MSG/Ob mice. The PPAR-γ and PPAR-α liver expression was repressed in both groups of mice, while the expression of PPAR-δ decreased only in lean mice. Interestingly, glycine treatment also suppressed the expression of UCP-2, TNF-α and IL-6 in lean mice, and increased adiponectin and insulin serum levels. In conclusion, glycine regulates the production of inflammatory cytokines through PPAR-γ. These results provide clues on glycine signaling mechanisms as an anti-inflammatory agent that might be useful for treatment of metabolic and vascular complications associated to inflammation in obesity.     

PPAR受体双重/泛激动剂存在的问题及前景

过氧化物酶体增殖物激活受体(PPAR)是一类配体依赖的核转录因子,属于核受体超家族。目前单纯的PPARγ激动剂类药物并不能有效预防糖尿病心血管并发症,而PPARα/γ双重激动剂能在增加胰岛素敏感性的同时还能预防心血管并发症。这类化合物正在临床试验并计划用于治疗伴有心血管并发症的2型糖尿病。研究发现,PPARα/γ双重激动剂具有意想不到的不良反应,这给临床应用带来了一系列的问题。现就PPAR受体双重/泛激动剂研究和发展中存在的问题及前景进行分析。     

小檗碱对糖尿病大鼠心肌PPARs表达的影响(英文)

目的观察小檗碱对糖尿病大鼠心脏重 / 体重比值、心肌病理结构改变和 PPARα/γ/δ蛋白表达的影响。方法注射链脲菌素（ 35 mg/kg, ip） 加高糖高脂饲料喂养 16 周建立 2 型糖尿病大鼠模型, 随后 16 周每天分别给予低中高剂量小檗碱（ 75、150、300 mg/kg） 、非诺贝特（ 100 mg/kg） 和罗格列酮（ 4 mg/kg） , 用 HE 染色检查心肌结构病变和免疫组化技术检测 PPARα/γ/δ的表达。结果小檗碱明显降低糖尿病大鼠的心脏重/ 体重比值（ P〈0.01） , 改善心肌肥厚和纤维化空泡。在心肌中几乎检测不到 PPARγ蛋白表达, 中高剂量小檗碱和非诺贝特能恢复糖尿病心肌中降低了的 PPARα和 PPARδ表达至正常大鼠水平（ P〈0.01） 。结论小檗碱调控心肌 PPARα/δ蛋白的表达可能是其降低心脏重 / 体重比值和改善糖尿性心肌结构改变的机制之一。     

An overview of the effect of linoleic and conjugated-linoleic acids on the growth of several human tumor cell lines

Both n-6 and n-3 polyunsaturated fatty acids are dietary fats important for cell function, being involved in several physiologic and pathologic processes, such as tumorigenesis. Linoleic acid and conjugated linoleic acid, its geometrical and positional stereoisomer, were tested on several human tumor cell lines originating from different tissues and with different degrees of malignancy. This was to provide the widest possible view of the impact of dietary lipids on tumor development. While linoleic acid exerted different effects, ranging from inhibitory to neutral, even promoting growth, conjugated linoleic acid inhibited growth in all lines tested and was particularly effective against the more malignant cells, with the exception of mammary tumor cells, in which behavior was the opposite, the more malignant cell line being less affected. The inhibitory effect of conjugated linoleic acid on growth may be accompanied by different contributions from apoptosis and necrosis. The effects of conjugated linoleic acid on growth or death involved positive or negative variations in PPARs. The important observation is that a big increase of PPARalpha protein occurred in cells undergoing strong induction of apoptosis, whereas PPARbeta/delta protein decreased. Although PPARalpha and PPARbeta/delta seem to be correlated to execution of the apoptotic program, the modulation of PPARgamma appears to depend on the type of tumor cell, increasing as protein content, when inhibition of cell proliferation occurred. In conclusion, CLA may be regarded as a component of the diet that exerts antineoplastic activity and its effect may be antiproliferative or pro-apoptotic.     

Dose-dependent effects of soy phyto-oestrogen genistein on adipocytes: mechanisms of action

The potential role of genistein in the prevention and treatment of obesity has attracted much attention among public and medical communities. Conversely, increasing evidence indicates that genistein as an endocrine-disrupting substance is likely to play a role in the aetiology of obesity. This review focuses on the role of soy phyto-oestrogen genistein in adipocytes and the underlying mechanisms of action. Genistein dose-dependently inhibits and stimulates adipogenesis in vitro . Increasing evidence shows that genistein dose-dependently influences obesity in both male and female animals. Dose-dependent effects of genistein on adipocytes vary with factors such as age and gender of animals. In addition, the role of developmental exposure of genistein in adult obesity has been discussed. Genistein, different from oestrogen, concurrently activates nuclear receptors, oestrogen receptors and peroxisome proliferator-activated receptors, and it inhibits various enzyme activities. The balance among these pleiotrophic effects of genistein determines its dose-dependent effects on adipocyte differentiation and function. Current data suggest that genistein could regulate adiposity. However, it remains uncertain whether genistein plays a beneficial role in the prevention and treatment of obesity. Additional evidence is required before firm conclusions showing that genistein decreases adiposity.