ω-3多不饱和脂肪酸对改善荷瘤大鼠营养状况的作用

目的:通过建立大鼠肿瘤动物模型,比较含ω-3多不饱和脂肪酸(PUFA)和ω-6 PUFA的不同肠外营养支持对大鼠肿瘤及机体营养状况的影响.方法:实验动物随机分为4组,对其中3组用Walker 256肉瘤细胞株建立肿瘤动物模型,通过颈静脉置管分别对其中2组实施含ω-3 PUFA及ω-6 PUFA的营养支持.最终测定血清IL-6、TNF-α及白蛋白浓度,使用Western印迹法测定Atrogin-1基因蛋白的表达量.研究期间隔日记录大鼠体重改变.结果:ω-3 PUFA组大鼠的体重丢失少于荷瘤大鼠组[(-21.30±2.95)g比(-26.80±1.03)g;P=0.009)].ω-3 PUFA组大鼠的血清IL-6浓度明显低于ω-6 PUFA组[(71.63±39.50)pg/mL比(141.72±98.32)pg/mL;P=0.002].ω-3 PUFA组大鼠的血清TNF-α浓度低于ω-6 PUFA组[(131.67±22.10)pg/mL比(167.26±37.98)pg/mL;P=0.007].ω-3 PUFA组大鼠Atrogin-1蛋白质的表达低于ω-6 PUFA组.结论:①运用ω-3 PUFA干预,可降低荷瘤大鼠的血清IL-6、TNF-α浓度;②运用ω-3 PUFA干预,可改善荷瘤大鼠体重、减轻荷瘤大鼠的体重丢失;③运用ω-3 PUFA干预,可使荷瘤大鼠的Atrogin-1基因蛋白质表达减少,改善机体的骨骼肌蛋白消耗.     

Effects of omega-3 fatty acid supplementation on vascular access thrombosis in polytetrafluorethylene grafts.

OBJECTIVE: The purpose of this study was to investigate the effects of orally administered over-the-counter omega-3 (n-3) fatty acid supplements on primary patency of polytetrafluoroethylene (PTFE) grafts. DESIGN: This study was conducted with a triple-blind, permuted-block, randomized, placebo-controlled experimental design. SETTING: Dialysis clinics with patients who, in accordance with physician diagnosis, needed a new PTFE graft. PATIENTS AND OTHER PARTICIPANTS: Patients on long-term hemodialysis with newly placed PTFE grafts who were unable to receive a native arteriovenous fistula. INTERVENTION: Patients were followed prospectively for 8 months after they had been placed into an n-3 fatty acid or control group and were monitored for primary patency. MAIN OUTCOME VARIABLE: Primary patency of the PTFE graft. RESULTS: The n-3 fatty acid group had a mean PTFE graft primary patency rate of 254.2 days (SEM = 51.8), and the control group had a mean PTFE graft primary patency rate of 254.1 days (SEM = 34.6), revealing no significant difference in survival time between groups. CONCLUSIONS: No significant differences in primary patency rates were noted in the experimental and control groups.     

大鼠肝移植术后输注ω-3多不饱和脂肪酸对T淋巴细胞的影响

目的 探讨大鼠肝移植术后应用ω-3多不饱和脂肪酸对移植肝脏功能、受体T淋巴细胞和急性排斥反应的影响.方法 行BN(RTln)大鼠到Lewis(RT11)二袖套法大鼠肝移植18例,术后颈内静脉插管,微量泵匀速输注液体.生理盐水NS组(n=6)输注生理盐水,肠外营养PN组(n=6)输注营养液,脂肪酸OM组(n=6)输注营养液+ω-3脂肪乳.术后第7天处死大鼠,留取肝组织标本病理检查,取血清检测生化指标.取抗凝血0.5 ml,流式细胞仪检测CD4+、CD8+、CD4+CD25+T细胞和CD8+CD28-T细胞.结果 大鼠肝移植术后输注ω-3脂肪酸的OM组CD4+、CD8+、CD4+CD25+和CD8+CD28-T细胞下降,与Ns组比较差异有统计学意义(t=4.28,P<0.01;t=2.63,P<0.05;t=2.59,P<0.05;t=8.86,P<0.01).OM组CD4+、CD8+、CD4+CD25+和CD8+CD28-T细胞下降,与PN组比较差异有统计学意义(分别t=8.06,t=3.57,t=5.35.t=7.98,均P<0.01).OM组CD4+/CD8+比值下降,与NS组和PN组比较差异有统计学意义(分别t=2.41,t=8.74,均P<0.01).病理学检查移植肝排斥反应强度(rejection activity index,RAI)评分,NS组为7.17±0.98,PN组为6.17±0.75,OM组为4.33±0.52,OM组与NS组、PN组比较排斥反应减轻(分别t=6.25,t=4.92,均P<0.01).结论 静脉输注ω-3多不饱和脂肪酸可以抑制T淋巴细胞,显著降低CD4+辅助性T细胞比例,减轻排斥反应.抑制性T细胞和调节性T细胞与ω-3脂肪酸减轻大鼠肝移植排斥反应的效应无关.     

Effects of omega-3 fatty acids on acute necrotizing pancreatitis in rats

The aim of this study was to investigate the influence of omega-3 fatty acids (omega3FA) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increases in mortality rate, intestinal permeability, bacterial infection in pancreas and extrapancreatic organs, and serum activity of urea and amylase, alanine transferase (ALT), interleukin (IL)-6, tumor necrotizing factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and a considerable decrease of concentrations of calcium, protein and albumin. The use of omega3FA reduced mortality, phenol sulfophthalein excretion in urine, bacterial infection in pancreas, liver, spleen, MPO and MDA levels in pancreatic and lung tissue, LDH level in BAL fluid and serum IL-6 and TNF-alpha values. Serum triglyceride increased only in the omega3FA groups. Serum amylase, ALT, calcium, urea, protein, IL-1, and degree of pancreatic damage indicated no difference between the pancreatitis groups. Increased intestinal permeability and cytokine levels, and free radical damage play an important role during the course of acute pancreatitis. The treatment with omega3FA improves these effects. omega3FA may be useful in the treatment during ANP in rats. Therefore, it can be beneficial in patients with pancreatitis.     

Gallic acid and omega-3 fatty acids mitigate epididymal and testicular toxicity in manganese-treated rats

Environmental contamination by manganese is correlated with diverse health outcomes plus reproductive dysfunction. Dietary gallic acid (GA) and omega-3 fatty acids (ω-3-FA) are well reported to elicit beneficial health effects. Though, information on GA and ω-3-FA effects on manganese-induced reproductive toxicity is absent in literature. We examined the effect of GA or ω-3-FA on manganese-induced epididymal and testicular toxicity in rats, exposed to manganese (15 mg/kg b.w.) alone, in combination with GA (30 mg/kg b.w.) or ω-3-FA (20 mg/kg b.w.) by gavage for 14 consecutive days. GA or ω-3-FA significantly (p < .05) prevented manganese-mediated increase in lipid peroxidation, myeloperoxidase activity, reactive oxygen and nitrogen species production but increased antioxidant enzymes activities and glutathione level in epididymis and testes treated rats. GA or ω-3-FA enhanced the activities of testicular function marker enzymes, namely acid phosphatase (ACP), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and glucose-6-phosphate dehydrogenase (G6PD) in the treated rats. GA or ω-3-FA amelioration of manganese-induced decreases in follicle-stimulating hormone, luteinising hormone, and testosterone levels were complemented by increase (p < .05) sperm functional characteristics in treated rats. Conclusively, GA or ω-3-FA may serve as dietary supplements to improve male reproductive dysfunction associated with manganese toxicity.     

Impact of dietary fatty acid supplementation on renal injury in obese Zucker rats

We previously reported that renal injury in hyperlipidemic, obese Zucker rats was associated with a relative deficiency of tissue polyunsaturated fatty acids (PUFA). In the present study 10-week-old obese Zucker rats were pair fed regular chow or chow containing either 20% sunflower oil rich in n-6 PUFA, fish oil rich in n-3 PUFA, coconut oil medium-chain saturated fatty acid, or beef tallow long-chain saturated fatty acid. At 34 weeks of age there were comparable reductions in albuminuria, mesangial matrix expansion, and glomerulosclerosis in the fish oil and sunflower oil groups. While both fish oil and sunflower oil reduced serum triglycerides, and improved the composition of triglyceride-enriched lipoproteins, only fish oil decreased serum cholesterol. The effect of the dietary fatty acid supplementation on fatty acid profiles were similar in isolated glomeruli and cortical tissue. In general, the amelioration in injury in the fish oil and sunflower oil fed rats was most closely linked to glomerular levels of PUFA, either n-6 or n-3. These data suggest that hyperlipidemia and abnormalities in tissue FA are closely linked, and that dietary supplementation with PUFA may ameliorate chronic, progressive renal injury.     

Cardiac performance and plasma lipids of omega-3 fatty acid-treated streptozocin-induced diabetic rats

We studied the effect of omega-3 fatty acid (omega 3FA) treatment on plasma lipids and cardiomyopathy in the diabetic rat. The omega 3FA preparation used was Promega. Male Wistar rats (250-275 g) were rendered diabetic by streptozocin (STZ; 55 mg.kg-1). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to either a treated or untreated group. Promega was administered at a dose of 0.5 ml.kg-1.day-1 by oral gavage for 4 wk, after which the rats were decapitated, plasma collected, and isolated working heart performance studied. Promega treatment did not affect plasma glucose, triglyceride, or cholesterol concentrations of either the control or diabetic rats. Cardiac performance was assessed by measuring the left ventricular response to changing left atrial filling pressures (7.5-20 cm H2O). The treatment had no effect on peak left ventricular developed pressure (LVDP) or maximal rate of change of left ventricular pressure during systole (+dP/dtmax) or diastole (-dP/dtmax) in the nondiabetic control rats. LVDP and +/- dP/dt were significantly improved (P less than .05) in the treated diabetic rats compared with untreated diabetic rats, although cardiac performance did not improve to the nondiabetic level. Cardiac sarcoplasmic reticulum (SR) calcium transport activity was not affected by the treatment in the control rats but was significantly improved (P less than .05) in the treated diabetic rats. These data suggest that omega 3FA treatment partially blocks the development of experimental diabetic cardiomyopathy, possibly by affecting SR calcium transport activity.     

Plasma fatty acid composition in continuous ambulatory peritoneal dialysis patients: an increased omega-6/omega-3 ratio and deficiency of essential fatty acids

Patients with end-stage renal disease, including those treated with peritoneal dialysis, have a high risk for death, particularly from cardiovascular causes. Plasma fatty acid (FA) composition is used as an indicator of disease risk, because its alteration has been related to metabolic disease and cardiovascular disease. For this purpose, we have measured plasma FA composition in continuous ambulatory peritoneal dialysis (CAPD) patients and compared them with those of healthy subjects. This study was performed on 51 (21 M, 30 F) CAPD patients at least 6 months under dialysis, aged 20-75 years (mean 47.81 ± 11.8 years) and 45 (25 M, 20 F) healthy control subjects aged 20-60 years (mean 38.62 ± 12.9 years). Plasma 10-cis-pentadecanoic acid, 10-cis-heptadecanoic acid, heneicosanoic acid, tricosanoic acid, nervonic acid, saturated fatty acid, and monounsaturated FA levels and delta 9 desaturase activity were significantly higher whereas linoleic acid, linolenic acid, 11,14-eicosedienoic acid, arachidonic acid, docosahexaenoic acid, and omega-3 FA levels were significantly lower in the CAPD group than those in the healthy group. Our results show that there are FA abnormalities and especially a depletion in essential FA levels and a high level of omega-6/omega-3 ratio in CAPD patients, the underlying mechanism of which is not known and needs to be investigated. Therefore, we believe that essential FA supplementation should be encouraged for CAPD patients.     

Essential fatty acid diet supplementation. Effects on peripheral nerve and skeletal muscle function and capillarization in streptozocin-induced diabetic rats

Effects of essential fatty acids on nerve conduction, hypoxic resistance, skeletal muscle contractile properties, and capillary density were examined in streptozocin-induced diabetic rats. Nondiabetic and diabetic controls and three diabetic groups treated with 10% supplements of corn oil, evening primrose oil (Efamol), or a mixture of 80% evening primrose oil and 20% fish oil (Efamol Marine) for 2 mo were used. Efamol and Efamol Marine increased plasma gamma-linolenic acid levels, but arachidonic acid was elevated only with Efamol. Diabetes resulted in 15-29% reductions in sciatic motor and sensory saphenous nerve conduction velocity. Efamol prevented conduction deficits more effectively than Efamol Marine, and corn oil had no effect. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for action potential amplitude to decline by 50% with diabetes. Corn oil had no significant effect. With Efamol, hypoxic resistance was within the nondiabetic range. Efamol Marine produced intermediate results. Functional improvements may relate to enhanced vasa nervorum perfusion, because endoneurial capillary density increased by 22% with Efamol, angiogenesis perhaps resulting from eicosanoid production from arachidonic acid. Soleus muscle contractions were prolonged by diabetes. This was partially corrected by treatment, Efamol being most effective. Extensor digitorum longus muscle had reduced tetanic tension with diabetes, and this was prevented by all treatments. Soleus showed a modest increase in capillarization with Efamol, which may have contributed to reduced susceptibility to fatigue. The data suggest involvement of abnormal fatty acid metabolism in the etiology of diabetic neuropathy and myopathy.     

Dietary omega-3 fatty acids may be associated with increased neuropathic pain in nerve-injured rats

Certain dietary proteins and oils are capable of decreasing chronic neuropathic pain levels in rats after partial sciatic nerve ligation injury. We tested, for the first time, the role of dietary polyunsaturated fatty acids in suppressing pain in partial sciatic nerve ligation-injured rats. Six groups of male Wistar rats were fed an identical casein-based, fat-free diet for 1 wk preceding partial sciatic nerve ligation injury and for 1 wk thereafter. In addition, rats received, via gavage, 1 mL/day of pure canola, corn, hemp, soy, or sunflower oil, differing significantly in their omega-3 and omega-6 polyunsaturated fatty acid content, or 1 mL of plain water. Responses to tactile and noxious heat stimuli were recorded before and after surgery and a difference score was calculated for each group by subtracting the preoperative from the post-partial sciatic nerve ligation values. Heat hyperalgesia, but not tactile allodynia, was significantly different among the dietary groups (P = 0.005). Heat hyperalgesia of rats fed hemp oil, developing the most robust response, was significantly larger compared with rats fed corn oil, developing the least pain model (difference score: 24.3 +/- 4.1 s versus 6.1 +/- 3.1 s, respectively; P < 0.001). These oils contain similar levels of omega-6 polyunsaturated fatty acids (hemp, 60%; corn, 58%) but their omega-3 levels are 28-fold different (20% versus 0.7%, respectively). A significant correlation was found among dietary levels of omega-3, but not omega-6 or the omega-3/omega-6 ratio, of the six dietary groups and heat hyperalgesia (P = 0.006). We conclude that dietary oil might predict levels of neuropathic pain in rats and that this effect may be associated with dietary omega-3 levels. IMPLICATIONS: We found that certain commonly used oils can have a significant analgesic effect in rats with persistent pain after partial nerve injury. This effect may be associated with the amounts of omega-3 fatty acids consumed by rats.     

Effects of marine n‐3 fatty acid supplementation in renal transplantation: A randomized controlled trial

Marine n‐3 fatty acids (FAs) may exert beneficial effects on inflammation, fibrosis, and endothelial function, which could preserve renal graft function. In this randomized controlled trial, 132 Norwegian renal transplant recipients received either 2.6 g of marine n‐3 FAs or olive oil (control) daily for 44 weeks, in addition to standard care. Thirty patients did not complete the trial. The primary endpoint was change (Δ) in measured glomerular filtration rate (mGFR) during follow‐up. We found no significant difference in Δ mGFR between the marine n‐3 FA group and controls (6.7 vs 3.8 mL/min per 1.73 m², P = .15). Significant beneficial effects from marine n‐3 FA supplementation were, however, seen in secondary endpoints plasma triglycerides, plasma high‐sensitivity C‐reactive protein, and brachial artery flow‐mediated dilation. In the per‐protocol population, the renal graft indices percent interstitial fibrosis and Chronic Allograft Damage Index also were significantly lower in the marine n‐3 FA group. The cumulative incidence of adverse events did not differ between the marine n‐3 FA group (n = 218) and controls (n = 240). In conclusion, marine FA supplementation did not improve renal function compared with controls, but was safe, lowered plasma triglyceride and high‐sensitivity C‐reactive protein levels, and improved endothelial function (Clinical.Trials.gov identifier NCT01744067).