实验性糖尿病大鼠肝,肾,心,脑脂肪酸代谢的动态变化

报道对链脲佐菌素（STZ）诱导的实验性糖尿病大鼠几种重要脏器（肝、肾、心、脑）卵磷脂、脑磷脂中脂肪酸构成的变化。不饱和脂肪酸变化的模式（C18：2n-6，C20：3n-6，C22：5n-3，C22：6n-3增加，C20：4n-6降低）基本相同，改变的先后顺序是肝→心、肾→脑。     

Subchronic (13-week) oral toxicity study of dihomo-γ-linolenic acid (DGLA) oil in rats

Dihomo-γ-linolenic acid (DGLA) is one of the essential fatty acids, and has anti-inflammatory and anti-allergic effects. To assess the toxicity of a novel DGLA oil produced by the fungus Mortierella alpina, we examined it in the Ames test and in acute and subchronic oral toxicity tests in rats. In the Ames test, no mutagenicity was found up to 5000 μg/plate. The acute toxicity test revealed no toxicity related to DGLA oil at 10 g/kg. In the subchronic toxicity test, DGLA oil (500, 1000, and 2000 mg/kg) was orally administered. Water and soybean oil (2000 mg/kg) were used for the no-oil control and soybean oil control groups, respectively. There was no death in either sex. Because of administration of large amounts of oil, food consumption was low in the soybean oil control and the three test groups, which appeared to mildly decrease urinary excretion of Na, K, and Cl, as well as total serum protein, albumin, and blood urea nitrogen levels. There were no toxicological changes in body weight, food consumption, ophthalmological examination, urinalysis, hematological examination, blood biochemical examination, necropsy, organ weight, or histopathological examination. These findings show that the no-observed-adverse-effect level of the DGLA oil was 2000 mg/kg.     

A butter diet induces higher levels of n-3 PUFA and of n−3/n−6 PUFA ratio in rat serum and hearts than a safflower oil diet

The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not differ among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (p<0.005, respectively). Higher levels of α-tocopherol were found in the butter groups than in the safflower oil groups (p<0.05) and in the casein groups than in the soy protein groups (p<0.01). In comparison with the safflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (p<0.005). The ratios of n-3/n-6 PUFA in the butter groups in serum, 0.26 and 0.18, and in the hearts, 0.37 and 0.36, (butter-casein diet and butter-soy protein diet, respectively) were higher than those of the safflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (p<0.005). In the soy protein groups, higher n-3 PUFA contents in the hearts were found than those of the casein groups (p<0.05). This study suggested that the butter diet induces higher levels of n-3 PUFA and a higher n-3/n-6 PUFA ratio than the safflower oil diet in rat serum and hearts over a long feeding period.     

Elevated concentrations of linoleic acid in erythrocyte membrane phospholipids in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is a disorder characterized by diffuse inflammation of the gastrointestinal tract. The immune response and inflammation are mediated by polyunsaturated fatty acids and influenced by dietary fats and lipid metabolism. This study examined the qualitative and quantitative fat intake of IBD patients and healthy controls on plasma phospholipid and erythrocyte membrane phospholipid (EMP) fatty acid content. Measurement of the fatty acid composition of plasma phospholipid and EMP were performed in 29 UC patients, 20 CD patients, and 31 healthy controls. Anthropometric characteristics and data on dietary intake were also collected. We observed significantly lower lipid intake in UC and CD patients vs controls. The UC and CD patients had significantly higher levels of linoleic acid in their EMP than did controls. There were no significant differences in the levels of n-3 polyunsaturated fatty acids, but there were significantly higher levels of the n-6 in the EMP of UC and CD patients compared with controls. The significant differences persisted after the data were adjusted for potential confounders and lipid intake. Higher levels of linoleic acids and n-6 fatty acids, which are involved in production of proinflammatory mediators, were found in IBD patients compared with controls, thereby implicating n-6 fatty acids in the pathophysiology of the disease.     

The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial

STUDY OBJECTIVE: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. DESIGN: Multicenter, randomized, placebo controlled, double blind. SETTING: Three Danish hospital Departments of Rheumatology. PATIENTS: Fifty-one patients with active rheumatoid arthritis. INTERVENTION: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. MAIN RESULTS: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis.     

Cyclooxygenase-2 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer related mortality worldwide. The incidence of HCC is rising worldwide, especially in the United States. The overall survival of patients with HCC is grim and currently no efficient secondary prevention or systemic treatments are available. Recent evidence suggests that COX-2 signaling is implicated in hepatocarcinogenesis and COX-2 inhibitors prevent HCC cell growth in vitro and in animal models. However, given the recently reported side effect associated with some of the COX-2 inhibitors, it is imperative to develop chemotherapeutic strategy that simultaneously targets COX-2 and other related key molecules in hepatocarcinogenesis or to utilize agents inhibiting COX-2 signaling in conjunction with other standard chemotherapy or radiation therapy. Such combinational therapeutic approaches are expected to provide synergistic anti-tumor effect with lesser side effect. In this regard, the recently delineated interplay between COX-2-derived PG signaling and other growth-regulatory pathways such as EGFR, Met, iNOS, VEGF and n-3 polyunsaturated fatty acids is expected to provide important therapeutic implications. This review summarizes the recent advances in understanding the mechanisms for COX-2-derived PG signaling in hepatocarcinogenesis and focuses on the newly unveiled interactions between PG cascade and other key signaling pathways that coordinately regulate HCC growth. Understanding these mechanisms and interplays will facilitate the development of more effective chemopreventive and therapeutic strategies.     

ω-3多不饱和脂肪酸在严重脓毒症机械通气早期的保护作用的研究

目的 观察ω-3多不饱和脂肪酸在严重脓毒症机械通气早期的保护作用.方法 将32例严重脓毒症机械通气的患者随机分为对照组（17例）和治疗组（15例）.使用等氮、等热量肠内及肠外混合营养共5 d,热量为113 kJ（27 kcal）/（kg·d）.对照组病人用中长链脂肪乳剂,研究组病人用ω-3鱼油脂肪乳＋中长链脂肪乳剂.分别在试验开始前和试验第6天早晨,抽血检测白细胞数、总蛋白、白蛋白、MDA、血浆C反应蛋白、血气分析指标（动脉氧分压、动脉二氧化碳分压氧合指数）,同时记录患者临床体征（心率、呼吸、体温）及进行APACHEⅡ评分.结果 添加鱼油脂肪乳的患者呼吸情况（17.13±3.78）次/分、氧合情况（251.27±52.68）、CRP（46.13±25.33）及APACHEⅡ评分（ 14±3.67）分及MDA（7.95±2.48）分,较对照组明显改善（P〈0.05）.结论 ω-3多不饱和脂肪酸在严重脓毒症机械通气患者早期应用可以降低患者体内过渡的炎症反应,减少氧化应激产物的生成,改善患者的氧合情况.     

Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells

The role of cyclooxygenase-2 (COX-2) and the mechanism by which it influences the development and behavior of prostate cancer is unclear. Selective COX-2 inhibitors may be effective against prostate cancer via COX-2-independent mechanisms. But administration of high doses of COX-2 inhibitors over longer period of time may not be devoid of side effects. There is increasing interest in using COX-2 inhibitors in combination with other chemopreventive agents to overcome the issue of toxicity. However, the molecular mechanisms underlying their combined actions are not well understood. Therefore, the present study was designed to determine the effects of low doses of docosahexaenoic acid (DHA) in combination with celecoxib on the molecular targets at the proteins level in rat prostate cancer cells. Two-dimensional gel electrophoresis, in combination with mass spectrometry analysis, was used for protein identification. Western blot analysis confirmed the proteins identified. Paraffin-embedded tissue sections from the rat prostate tumor were used to detect base level expression of heat shock protein 70 (HSP70) and p53. The rate of cancer cell growth was inhibited more effectively (p < 0.01) by DHA in combination with celecoxib at lower doses (2.5 microM each). A total number of twelve proteins were differentially expressed by the combined action of DHA and celecoxib at low doses. It was interesting to note that these agents activated both HSP70 and p53 proteins. Activation of HSP70 by the combined actions of DHA and celecoxib in the presence of wild-type p53 reveals a unique COX-2 independent mode of action against prostate cancer.     

Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: Docosahexaenoic acid or eicosapentaenoic acid

Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as cancers. As chronic inflammations are associated with malignancies, it is important to prevent inflammation-mediated neoplastic formation, promotion and/or progression. One possible intervention will be using cancer chemopreventive agents such as curcumin (CUR), a potent anti-inflammatory and anti-oxidative stress compound. Polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) are potent anti-inflammatory agents by decreasing the production of inflammatory eicosanoids, cytokines, and reactive oxygen species (ROS). The present study aims at examining whether CUR with DHA or EPA would have synergistic anti-inflammatory effects in RAW 264.7 cells. Non-toxic concentrations of single and combination of the compounds were investigated at 6, 12 and 24 h. The nitric oxide (NO) suppression effects were most prominent at 24 h. All the combinations of CUR and DHA or EPA with lower concentrations of CUR 5 μM and 25 μM of DHA or EPA were found to have synergistic effects in suppressing LPS-stimulated NO and endogenous NO levels. Importantly, very low doses of CUR 2.5 μM and DHA or EPA of 0.78 μM could synergistically suppress the LPS-induced prostaglandin E₂ (PGE₂). The combinations were also found to suppress iNOS, COX-2, 5-lipoxygenase (5-LOX) and cPLA₂ but induce HO-1. Taken together, the present study clearly shows the synergistic anti-inflammatory as well as anti-oxidative stress effects of CUR and PUFA.     

Do Pregnant Women and Those at Risk of Developing Post-Natal Depression Consume Lower Amounts of Long Chain Omega-3 Polyunsaturated Fatty Acids?

The aims were to compare intakes of long chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) in pregnant and non-pregnant women in Australia and to compare these intakes to the Australian National Nutrition Survey of 1995 (NNS95) [1] and to determine if the LC n-3 PUFA intakes differed in women who may be 'at risk' compared with women 'not at risk' of developing post-natal depression (PND). A validated LC n-3 PUFA food frequency questionnaire and pregnant women's Edinburgh Postnatal Depression Scale (EPDS) scores were used. LC n-3 PUFA intakes were comparable to the NNS95 but did not differ due to pregnancy or whether or not a woman is at risk of developing PND.