The cyclopentenone prostaglandin 15-deoxyΔ12,14-prostaglandin J2 attenuates the development of zymosan-induced shock

Objective Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. This study investigated the effect of 15-deoxy-^12,14-PGJ₂ (15d-PGJ₂), a PPAR- ligand, in a model of zymosan-induced nonseptic shock in mice.Materials and methods Mice were randomly assigned to one of four groups (n=10 each) and treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline solution) plus 15d-PGJ₂ (30 µg/kg, suspended in 10% DMSO) 1 h before and 6 h after zymosan administration; group 3, 15d-PGJ₂ (30 µg/kg, suspended in 10% DMSO; group 4, vehicle for PGJ₂ (10% DMSO) always 1 h before and 6 h after saline administration. After 18 h mice were killed and tissues and biological fluids used for biochemical, immunohistochemical, and histological analysis.Measurements and results 15d-PGJ₂ inhibited the inflammatory response and significantly reduced peritoneal mononuclear cell infiltration and histological injury in mice. A significant protection was demonstrated in kidney, liver, and pancreas injury by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubin, and alkaline phosphatase levels. 15d-PGJ₂ also reduced the appearance of nitrotyrosine in the inflamed intestinal tissues. Histological examination revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ₂ treated mice.Conclusions Our findings demonstrate that 15d-PGJ₂ exerts potent anti-inflammatory effects on zymosan-induced shock.Electronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

红景天提取物对胰岛素抵抗大鼠肝脏过氧化物酶体增殖物激活受体-γmRNA 表达的影响

目的：观察中药红景天提取物对高脂饮食诱导的胰岛素抵抗大鼠胰岛素敏感性及过氧化物酶体增殖物激活受体-γ（ PPAR-γ） mRNA表达的影响。方法将70只Wistar大鼠随机分为2组,正常对照组20只,高脂模型组50只。正常对照组给予基础饲料,高脂模型组给予高脂饲料,均喂养4周后2组各随机选取10只大鼠行高胰岛素-正葡萄糖钳夹试验判断造模是否成功,确认造模成功后将剩余高脂模型组大鼠随机分为高脂对照组和高脂＋红景天干预组,每组20只。高脂＋红景天干预组给予红景天提取物1 g/（ kg ＆#183; d）灌胃,正常对照组及高脂对照组给予等容积0．9％氯化钠注射液灌胃,其他饲养条件不变,继续喂养4周。观察比较各组大鼠造模后和灌胃4周后血清甘油三酯（ TG）、血清总胆固醇（ TC）、游离脂肪酸（ FFA）、空腹血糖（ FPG）及空腹血清胰岛素（ FINS）的含量变化,并记录葡萄糖输注率（ GIR）变化及PPAR-γmRNA的表达情况。结果高脂模型组大鼠造模后与正常对照组比较FPG、FINS明显升高（P＜0．05）,GIR明显下降（P＜0．05）;高脂对照组灌胃4周后与正常对照组比较TG、TC及FFA水平均明显升高（P＜0．05）,高脂＋红景天干预组较高脂对照组TC、TG及FFA水平均明显下降（P＜0．05）,与正常对照组水平相当（P＞0．05）;高脂对照组灌胃4周后与正常对照组比较FPG、FINS明显升高（P＜0．05）,GIR明显下降（P＜0．05）,高脂＋红景天干预组较高脂对照组FPG、FINS水平明显下降（P＜0．05）,GIR明显升高（P＜0．05）,与正常对照组水平相当相（P＞0．05）;高脂对照组灌胃4周后PPAR-γmRNA表达水平与正常对照组表达水平相当（P＞0．05）,高脂＋红景天干预组较正常对照组及高脂对照组比较PPAR-γmRNA表达水平均有明显升高（P＜0．05）。结论红景天提取物对大鼠的     

Cytokine-induced endogenous production of prostaglandin D2 is essential for human group 2 innate lymphoid cell activation

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PPAR-γ在多囊卵巢综合征大鼠脂肪组织中的表达及意义

目的:探讨过氧化物酶增殖物激活受体-γ(PPAR-γ)在多囊卵巢及正常大鼠脂肪组织中的表达及在多囊卵巢综合征(PCOS)发病中的作用。方法:应用脱氢表雄酮(DHEA)皮下注射23天龄SD雌性大鼠20天,建立PCOS大鼠模型,应用免疫组织化学技术对PPAR-γ在PCOS大鼠和对照组大鼠脂肪组织的表达强度变化进行研究。结果:PCOS大鼠模型建立成功;PPAR-γ在PCOS组脂肪组织基质细胞上的表达强度(102.7656±11.15510)明显低于对照组(146.3264±4.93102),P<0.001。结论:PPAR-γ在多囊卵巢大鼠发病中起着重要作用。     

Effect of the peroxisome proliferator perfluorodecanoic acid on growth and lipid metabolism in Sprague Dawley rats fed three dietary levels of selenium

The possible interrelationships between the effects of dietary selenium and perfluorodecanoic acid (PFDA) on growth and lipid metabolism were studied in the male Sprague Dawley rat. Rats were divided into groups and placed on diets containing three levels of selenium (0.04, 0.2, and 1.0 ppm as sodium selenite). Two weeks later, half the rats in each group received a single 35 mg/kg IP injection of PFDA in corn oil, while their pair-fed companion received only vehicle. Rats injected with PFDA stopped gaining weight, and weighed less than pair-fed controls, despite equal food intakes. Two weeks following PFDA administration the rats were killed and plasma cholesterol and triglycerides, and liver peroxisomal enzyme activities were quantified. In contrast to other peroxisome proliferators, PFDA increased plasma triglycerides while decreasing plasma cholesterol. The rate of peroxisomal fatty acid -oxidation was decreased, even though the activity of fatty acyl-CoA oxidase, the first enzyme in the peroxisomal fatty acid -oxidation pathway, was increased. Dietary selenium, other than increasing the liver to body weight ratio, did not alter growth or lipid metabolism. This study demonstrates, for the first time, the existence of a non-hypotriglyceridemic peroxisome proliferator-PFDA.     

Pioglitazone does not increase cerebral glucose utilisation in a murine model of Alzheimer’s disease and decreases it in wild-type mice

Aims/hypothesis Clinical trials are in progress to test thiazolidinediones in neurodegenerative diseases such as Alzheimer’s disease that involve deficiencies in brain glucose metabolism. While thiazolidinediones enhance glucose uptake in non-cerebral tissues, their impact on brain energy metabolism has not been investigated in vivo. We thus determined whether the thiazolidinedione pioglitazone reverses the decrease in cerebral glucose utilisation (CGU) in a model of brain metabolic deficiency related to Alzheimer’s disease. Results are relevant to diabetes because millions of diabetic patients take pioglitazone as an insulin-sensitising drug, and diabetes increases the risk of developing Alzheimer’s disease.Materials and methods The regional pattern of CGU was measured with the 2-deoxy [¹⁴C] glucose autoradiographic technique in adult awake mice overexpressing transforming growth factor β1 (TGFβ1), and in wild-type littermates. Mice were treated with pioglitazone for 2 months.Results Measurement of CGU in 27 brain regions confirmed that TGFβ1 overexpression induced hypometabolism across the brain. Pioglitazone did not reverse the effect of TGFβ1 overexpression and decreased regional CGU in control animals by up to 23%. The extent of the regional CGU decrease induced by pioglitazone, but not that induced by TGFβ1, correlated strongly with basal CGU, suggesting that the higher the local metabolic rate the greater the reduction of CGU effected by pioglitazone.Conclusions/interpretation In contrast to its stimulatory effect in non-cerebral tissues, chronic treatment with pioglitazone decreases CGU in vivo. This evidence does not support the hypothesis that pioglitazone could act as a metabolic enhancer in Alzheimer’s disease, and raises the question of how thiazolidinediones could be beneficial in neurodegenerative diseases.     

Troglitazone attenuates hypoxia-induced injury in cultured term human trophoblasts

OBJECTIVE: The purpose of this study was to test the hypothesis that the thiazolidinedione troglitazone, a peroxisome proliferator activated receptor-gamma ligand, attenuates hypoxia-induced trophoblast injury. STUDY DESIGN: Cytotrophoblasts from 4 term human placentas were cultured in the presence or absence of 10 mumol/L troglitazone in either 20% oxygen (standard conditions) or 1% oxygen (hypoxic conditions) for variable periods before cell harvest. Medium beta-human chorionic gonadotropin and human placental lactogen were analyzed by enzyme-linked immunosorbent assay. Apoptosis was quantified by cytokeratin-18 cleavage products staining; p53 expression was examined by Western blot analysis. RESULTS: beta-human chorionic gonadotropin and human placental lactogen levels were >/=2-fold higher in troglitazone-exposed cells at 16 hours of hypoxia, compared with vehicle control cells ( P <.05). The apoptotic index was reduced by >/=30% ( P <.001), and the expression of p53 was 2-fold lower ( P <.02) in troglitazone-exposed cells under hypoxia for 24 hours of low oxygen. CONCLUSION: Troglitazone attenuates the influence of acute hypoxia on cultured term human trophoblasts.     

Mutations affecting the expression of the MOX gene encoding peroxisomal methanol oxidase in Hansenula polymorpha

In this study, aimed at identifying genetic factors acting positively upon the MOX gene, we report the isolation and characterisation of several methanol utilisation-defective (Mut⁻) mutants of Hansenula polymorpha. These fall into 12 complementation groups, eight of which show significant reductions in alcohol (methanol) oxidase activity in methanol. Three of these groups, identifying the MUT3, MUT5 and MUT10 loci, exhibit extremely low levels of MOX promoter activity, not only in methanol medium, but also during growth in glycerol or methylamine. We suggest that these loci play a significant role in the derepression of the MOX gene expression. One of these genes (MUT10) also seems to be involved in the utilisation of carbon sources other than methanol, and it is apparent that the same gene plays some role in the biogenesis or in the enlargement of the peroxisome. Three other genes (MUT7, MUT8 and MUT9) appear to be involved in peroxisome biogenesis, whereas most other mutants harbour lesions that leave the peroxisome biogenesis and proliferation unaffected. Received: 8 March 2000 / Accepted: 9 May 2000