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1.
目的: 探讨大鼠小肠移植后移植肠发生慢性排斥时,口服n-3多不饱和脂肪酸对移植肠黏膜细胞凋亡、颗粒酶B和穿孔素表达的调控作用. 方法: 将大鼠分为三组:①Lewis- Lewis组,口服玉米油;②F344-Lewis组,口服玉米油;③F344-Lewis组,口服鱼油.所有受鼠在移植术后16周取材检测.用流式细胞法检测肠黏膜细胞凋亡,RT-PCR法检测穿孔素和颗粒酶的表达. 结果: 慢性排斥发生后,移植肠黏膜细胞凋亡率、颗粒酶B和穿孔素的表达明显增加.口服鱼油可抑制移植肠黏膜细胞的凋亡、颗粒酶B和穿孔素的表达. 讨论: 口服n-3多不饱和脂肪酸能抑制慢性排斥期移植肠的排斥反应,提高受鼠和移植物的存活率,延缓移植物的慢性失功.  相似文献   

2.
目的探讨外周血淋巴细胞(PBL)穿孔素和颗粒酶B表达水平在肾移植诊断急性排斥反应(AR)和抗排斥疗效中的关系。方法采用定量逆转录PCR(RT-PCR)方法动态测定AR(n=7)、肾功延迟恢复(n=8)、近期肾功正常(n=27)、长期肾功稳定(n=25)组67例肾移植患者移植前后PBL穿孔素和颗粒酶B表达水平和AR的关系。结果肾移植术后患者PBL穿孔素和颗粒酶B表达强度依次为AR组、肾功延迟恢复组、近期肾功正常组、长期肾功稳定组,AR组与其它3组差异有统计学意义(P<0.01);其升高时间比临床上出现AR的症状早约3d,随着AR的逆转,其表达也逐渐降至原有基础水平。结论定量RT-PCR测定PBL穿孔素和颗粒酶B的表达可以是一种无创的、较敏感的早期诊断肾移植AR的方法,并可预测抗排斥反应治疗效果。  相似文献   

3.
目的探讨外周血淋巴细胞(PBL)穿孔素和颗粒酶B表达水平在肾移植诊断急性排斥反应(AR)和抗排斥疗效中的临床价值。方法采用定量逆转录PCR(RT-PCR)方法动态测定AR(7例)、肾功延迟恢复(8例)、近期肾功正常(27例)、长期肾功稳定(25例)的肾移植患者移植前后PBL穿孔素和颗粒酶B表达水平和AR的关系。结果肾移植术后患者PBL穿孔素和颗粒酶B表达强度依次为AR组、肾功延迟恢复组、近期肾功正常组、长期肾功稳定组,AR组与其他三组比较差异有统计学意义(P<0.01);其升高时间比临床上出现AR的症状早3d左右,随着AR的逆转,其表达也逐渐降至基线水平。结论定量RT-PCR测定PBL穿孔素和颗粒酶B的表达是一种无创、较敏感的早期诊断肾移植AR的方法,可以预测抗排斥反应的治疗效果。  相似文献   

4.
目的 研究FTY720对同种异体大鼠小肠移植慢性排斥的作用及可能作用机制.方法 以F344大鼠为供体,Lewis大鼠为受体,建立小剂量环孢霉素诱导F344-to-Lewis大鼠小肠移植慢性排斥模型.实验分为四组,Ⅰ组为对照组,n=7;Ⅱ组为FTY720组,n=8;Ⅲ组为环孢霉素A(CsA)组,n=8;Ⅳ组为FTY720+CsA组,n=8.术后八周行移植物组织病理学评分和ELISA法测定血清中移植物细胞因子IL-2,IL-4,IL-6,IL-10以及TNFα,IFNγ的表达.结果 术后八周移植物组织病理学评分,Ⅱ组、Ⅳ组与对照组比较均明显改善.但是仅血管硬化评分:Ⅳ组与对照组比较,差异具有显著性(P<0.05).术后血清(IL-10、IFNγ)与移植物(IL-10),Ⅱ组、Ⅳ组与对照组比较具有显著性差异(P<0.05).结论 单独使用FTY720或联用CsA具有改善大鼠小肠移植慢性排斥血管硬化以及促进Th1/Th2平衡趋向Th2表达的趋势的免疫保护作用.  相似文献   

5.
OBJECTIVE: Polyunsaturated fatty acid supplementation may produce beneficial effects after surgery. We investigated the influence of preoperative administration of a supplement rich in arginine, omega-3 fatty acids, and RNA, Impact (Japan), on inflammatory and immune responses in patients undergoing major surgery for cancer. METHODS: Patients in the supplement group (n = 12) received 1 L/d of Impact (Japan) for 5 d before surgery, and those in the control group (n = 14) received an ordinary diet without Impact (Japan) before surgery. Plasma levels of omega-3 and omega-6 fatty acids, thromboxane B(2), prostaglandin E(2), inflammatory markers, nutritional markers, cytokines, and cytokine receptors were obtained 5 d before the operation at the starting point of supplementation in the supplement group. Samples were collected on postoperative days (PODs) 0, 1, 3, and 7. RESULTS: After taking the supplement, significant increases in omega-3 fatty acids and rapid turnover proteins were found the day after ending supplementation (POD-0), whereas thromboxane B(2) levels and the ratio of omega-6 fatty acids to omega-3 fatty acids were significantly lower than before supplementation (P < 0.001). On POD-0 only, inflammatory markers and cytokine receptors in the supplement group showed low levels in comparison with the control group (P < 0.05). On POD-1 and POD-3, remarkable decreases in polymorphonuclear leukocyte-elastase and interleukin-8 in the supplement group were observed. CONCLUSION: Our findings suggest that oral administration of a supplement rich in omega-3 fatty acids for 5 d before surgery may improve not only preoperative nutritional status but also preoperative and postoperative inflammatory and immune responses in patients who have cancer.  相似文献   

6.
Clinical and experimental evidence has supported a benefit for the inclusion of fish oils (a primary source of omega-3 fatty acids) as a component of a normal healthy diet. Polyunsaturated omega-3 fatty acids have been demonstrated to be of benefit in a number of inflammation-associated disease states, including atherosclerosis, autoimmune disorders, malignancy, and sepsis. The beneficial effects of omega-3 fatty acids are thought to occur through the postulated antiinflammatory actions of omega-3 fats; however, the specific mechanism(s) of action has not been completely defined. In this review, we discuss the recent progress made in our laboratory on defining the mechanisms of omega-3 fatty acids activity.  相似文献   

7.
A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many chronic diseases, including cardiovascular disease. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phopholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have strong anti-inflammatory effects, suppress interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids tend to be pro-inflammatory. Because inflammation is at the base of many chronic diseases, including coronary heart disease, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Increased dietary arachidonic acid (AA) significantly enhances the apparent atherogenic effect of genotype, whereas increased dietary intake of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blunts this effect. The diet-gene interaction further suggests that dietary omega-6 fatty acids promote, whereas marine omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.  相似文献   

8.
BACKGROUND & AIMS: Spontaneous bacterial infection and septicemia due to increased bacterial translocation (BT) in patients with obstructive jaundice result in significant morbidity and mortality. The present study evaluates the effects of enteral nutrition with immune enhancing feeds on BT and intestinal villus histopathology promoted by obstructive jaundice. METHODS: Fifty male Wistar-albino rats weighing 250-300g were assigned into five equal groups of 10. Animals in Groups I, II, and III were fed with standard chow, those in Group IV were given glutamine 1g/kg/day and the remaining 10 animals in Group V were fed with an arginine, omega-3 fatty acids, and RNA-supplemented enteral diet for (1g/kg/day amino acid and 230 kcal/kg) 7 days preoperatively. Group I underwent sham operation and the remaining animals in all other groups underwent common bile duct ligation. After operation, Group I had standard chow, Groups II and IV had glutamine, Groups III and V had an arginine omega-3 fatty acids, and RNA-supplemented enteral diet for 7 days. All animals were sacrificed on the 8th postoperative day and evaluated both biochemically and histopathologically. Samples from blood, liver, mesenteric lymph nodes and spleen were cultured under aerobic conditions. RESULTS: Significantly less BT was observed in groups fed with an arginine, omega-3 fatty acids, and RNA-supplemented enteral diet or glutamine in pre-and postoperative periods as compared to others (P<0.001). Histologic evaluation also showed significant reduction in villus atrophy in these groups. CONCLUSIONS: Enteral immunonutrition using glutamine or arginine, omega-3 fatty acids, and RNA-supplemented enteral diet during both pre-and postoperative periods seems to reduce BT and decrease atrophy of intestinal mucosal villi in rats with obstructive jaundice.  相似文献   

9.
慢性病毒性肝炎(乙型和丙型)的炎症过程是免疫介导所致,涉及到CTL和NK细胞。穿孔素/颗粒酶是上述细胞重要的效应物质,与细胞凋亡有关。此文对穿孔素/颗粒酶的分子结构、生物学特性及其在肝细胞损伤中的作用进行综述。  相似文献   

10.
Background: The aim of this study was to examine the anti-inflammatory and anti-apoptotic patterns of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during methotrexate (MTX) induced intestinal damage in cell culture and in a rat model. Methods: Non-treated and treated with MTX HT 29 and HCT116cells were exposed to increasing doses of n-3 PUFAs and cell viability was evaluated using PrestoBlue® assay. Male Sprague-Dawley rats were divided into 4 experimental groups: Control rats, CONTR+n-3 PUFA rats that were treated with oral n-3 PUFA, MTX rats were treated with MTX given IP, and MTX+n-3 PUFA rats were treated with oral n-3 PUFA before and following injection of MTX. Intestinal mucosal parameters and mucosal inflammation, enterocyte proliferation and apoptosis, TNF-α in mucosal tissue and plasma (ELISA), NF-κB, COX-2, TNF-α, Fas, FasL, Fadd, Bid, Bax and Bcl-2gene and protein levels were determined 72 h following MTX injection. Results: Exposure of HT 29 and HCT116cells to n-3 PUFA attenuated inhibiting effects of MTX on cell viability. MTX-n-3 PUFA rats demonstrated a lower intestinal injury score and enhanced intestinal repair. A significant decrease in enterocyte apoptosis in MTX+n-3 PUFA rats was accompanied by decreased TNF-α, FAS, FasL, FADD and BID mRNA levels. Decreased NF-κB, COX-2 and TNF-α levels in mucosa was accompanied by a decreased number of IELs and macrophages. Conclusions: n-3 PUFAs inhibit NF-κB/COX-2 induced production of pro-inflammatory cytokines and inhibit cell apoptosis mainly by extrinsic pathway in rats with MTX-induced intestinal damage.  相似文献   

11.

Background  

Polyunsaturated fatty acids are essential nutrients for humans. They are structural and functional components of cell membranes and pre-stages of the hormonally and immunologically active eicosanoids. Recent discoveries have shown that the long-chained omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also play an important role in the central nervous system. They are essential for normal brain functioning including attention and other neuropsychological skills.  相似文献   

12.
BACKGROUND: Irinotecan hydrochloride (CPT-11), a topoisomerase I inhibitor highly effective for various cancers, has its dosage limited by diffuse mucosal damage with increased prostaglandin (PG) E(2). However, an analysis of intestinal phospholipid fatty acid composition after CPT-11 treatment has not been reported. This study aimed to evaluate intestinal phospholipid fatty acid composition in relation to intestinal mucosal integrity and plasma and mucosal PGE(2) levels after CPT-11 treatment. The effect of dietary vegetable oil supplementation, perilla oil vs corn oil, was also evaluated. METHODS: Intestinal phospholipid fatty acid composition, PGE(2) level, mucosal diamine oxidase (DAO) activity, diarrhea, and blood tests were evaluated in rats injected with CPT-11 under a conventional diet. The same parameters were compared among 3 different dietary vegetable oil supplementations: perilla oil, corn oil, and a 1:3, respectively, mixture with a semisynthetic diet during 14 days. RESULTS: CPT-11 treatment caused severe diarrhea, and intestinal mucosal fatty acid composition changed with increased PGE(2) level and decreased DAO activity. Decreases in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA/arachidonic acid (AA) ratio in colonic mucosa were observed. Perilla oil increased omega-3 polyunsaturated fatty acids, alpha-linolenic acid, EPA, and EPA/AA ratio and decreased plasma PGE(2). But the amounts used were not enough to attenuate intestinal damage from CPT-11 treatment. CONCLUSIONS: CPT-11 induced changes of intestinal mucosal fatty acid composition with increased PGE(2) level and decreased intestinal integrity; perilla oil shows the possibility of being able to attenuate those changes.  相似文献   

13.
OBJECTIVES: We investigated the effects of conjugated linoleic acid (CLA) on tumor incidence, apoptosis, eicosanoid formation, 1,2-diacylglycerol (DAG), and fatty acid profiles of colonic mucosa in 1,2-dimethylhydrazine-treated rats fed different types of dietary fats. METHODS: One hundred twenty male 7-wk-old Sprague-Dawley rats were assigned to a beef tallow (BT) diet or a fish oil (FO) diet; each group was further divided into two groups, one with CLA supplementation (BTC and FOC) and the other without (BT and FO). All groups were fed for 30 wk on experimental diets that contained 12% (w/w) dietary fat (including 1% CLA for the BTC and FOC groups) and were intramuscularly injected with 1,2-dimethylhydrazine for 6 wk, for a total dose of 180 mg/kg of body weight. RESULTS: Rats fed the FOC, BTC, or FO (omega-3 fatty acids, mainly docosahexaenoic acid) showed a reduced incidence of tumors, increased apoptotic index values (P < 0.05), and lower levels of eicosanoids (prostaglandin E(2) and thromboxane B(2)) and DAG in colonic mucosa (P < 0.05). CLA and docosahexaenoic acid were incorporated into membrane phospholipids and significantly reduced the distribution of arachidonic acid in colonic mucosal phospholipids. Because CLA and omega-3 fatty acids reduced tumor incidence and levels of cell response regulators (prostaglandin E(2), thromboxane B(2), and DAG), they may share at least one common path of action in promoting the apoptotic process of colon carcinogenesis. CONCLUSIONS: These results suggested that increased apoptosis by dietary CLA may be attributed, at least in part, to changes in arachidonic acid metabolism in rats. Therefore, CLA may have anticarcinogenic effects by inducing apoptosis through modification of signal transduction in colonic mucosal cells.  相似文献   

14.
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Studies show that consumption of polyunsaturated fatty acids (PUFA) modulates the development and progression of prostate cancer. High amounts of omega-6 fatty acids have been linked with increased prostate cancer risk, whereas omega-3 fatty acids have been shown to inhibit PCa growth. However, because omega-3 and omega-6 are both essential fatty acids and part of a complete diet, it is more relevant to determine the ideal ratio of the two that would allow patients to benefit from the therapeutic properties of omega-3 fatty acids. LNCaP prostate cancer cells were treated with dietary-based ratios of omega-6 to omega-3 fatty acids under hormone-deprivation conditions, and effects on various cellular processes were determined. A low omega-6 to omega-3 PUFA ratio can delay the progression of cells toward castration-resistance by suppressing pathways involved in prostate cancer progression, such as the Akt/mTOR/NFκB axis. It also suppresses the expression of cyclin D1, and activation of caspase-3 and annexin V staining shows induction of proapoptotic events. Taken together, our data demonstrates that maintaining a low omega-6 to omega-3 fatty acids ratio can enhance efficacy of hormone ablation therapy.  相似文献   

15.
Omega-3 fatty acids from marine and plant sources provide a wide range of benefits in several human health conditions. In vivo studies indicate that omega-3 fatty acids influence the course of several human diseases, including those that involve abnormal immune function, mental disorders, and genetic abnormalities in lipid metabolism. Omega-3 fatty acids are taken up by virtually all body cells and affect membrane composition, eicosanoid biosynthesis, cell signaling cascades, and gene expression. These fatty acids are especially important during human brain development; maternal deficiency of omega-3 fatty acids may lead to several neurological disorders. The review highlights recent findings on omega-3 fatty acids' influence on autoimmune diseases, mental health, and gene expression.  相似文献   

16.
Polyunsaturated fatty acids (PUFAs) have an important role in human diet, both for the prevention and the therapy of different pathologies. In this review, a critical evaluation of PUFAs dietary sources and biological functions in human organism has been done. In particular, the efficacy of omega-3 fatty acids in the improvement of the lipidic pattern and in the excitability of myocardium has been analyzed, and, therefore, their usefulness in the prevention of cardiovascular diseases and postinfarction arrhythmias. As PUFAs are precursors of prostaglandins and leucotriens, which are involved in phlogosis and immune response, a diet rich in fish oil reduces the production of PGE2 involved in many phlogosis events. Moreover, an increase in the eicosapentaenoic acid (EPA) intake leads to a reduction in the production of inflammatory cytokines (interleukin 1, 2, 6 and tumor necrosis factor); so, it is important to use omega-3 in chronic inflammatory diseases, as the rheumatoid arthritis. It seems that omega-3 could prevent the onset of hormone-dependent tumours (i.e. breast and prostatic cancer); in vitro observations, in fact, have shown that the PG of the series 2, derived from omega-6, have a carcinogenic action; instead, the anticancer effect of omega-3 could derive from their effect in antagonizing the formation of such PG; it can be useful, therefore, to increase the dietary omega-3/omega-6 ratio. Moreover, the effects of omega-3 on the anatomic and functional central nervous system development and of their possible therapeutical use in some psychiatric pathologies were evaluated.  相似文献   

17.
OBJECTIVE: We investigated effects of Japanese torreya (Torreya nucifera) seed oil containing non-methylene-interrupted polyunsaturated fatty acid of all-cis-5,11,14-eicosatrienoic acid (sciadonic acid) on rat lipid metabolism. METHODS: Male Sprague-Dawley rats were fed the experimental diets based on AIN-93 containing 10% corn, soybean, or torreya oil for 4 wk. Blood and tissues were recovered from each rat, and concentrations of triacylglycerol, cholesterol, and phospholipid in plasma and liver were determined by enzymatic assays. Moreover, fatty acid composition was analyzed for triacylglycerol, cholesterol ester, and phospholipid isolated from plasma and liver lipids by gas liquid chromatography. RESULTS: Plasma triacylglycerol level in rats fed torreya oil was lower than that in rats fed corn or soybean oil, although there were no significant differences in plasma cholesterol and phospholipid levels in all rats. Liver triacylglycerol level was also lower in rats fed torreya oil, whereas liver cholesterol and phospholipid levers were same for all rats. omega-3 Polyunsaturated fatty acids such as 22:6 (omega-3) were lower in plasma and liver lipids of torreya and corn oil groups, whereas omega-6 polyunsaturated fatty acids such as 22:4 (omega-6) and 22:5 (omega-6) were higher. Considerable amounts of sciadonic acid were detected in cholesterol ester, triacylglycerol, and phospholipid in plasma and liver of rats fed torreya oil. CONCLUSION: These observations suggest that torreya seed oil can modify lipid metabolism, resulting in lower triacylglycerol levels in plasma and liver of rats.  相似文献   

18.
We studied the effects that dietary fat has on the capacity of preparations of rat small intestinal mucosal cells to metabolize benzo[a]pyrene (BP) in vitro and on the composition of fatty acids in the endoplasmic reticulum of the intestinal mucosa. When rats were fed diets containing different types of fat, there were significant changes in the incorporation of fatty acids into the endoplasmic reticulum of the mucosal cells of the small intestine: the proportions of polyunsaturated fatty acids in the endoplasmic reticulum reflected the amounts of these fatty acids in the dietary fat. The rate of BP oxidation in the intestinal mucosa was dependent on the amount and composition of the dietary fat, but the range and proportions of the metabolites produced were not affected. Dietary C18:2 was particularly important in elevating the rate of BP oxidation, but dietary C20:5 and C22:6 also effectively increased the rate of BP oxidation. The rate of BP oxidation in the small intestine of rats fed different diets was positively correlated with the proportion of polyunsaturated fatty acids in the endoplasmic reticulum of the mucosal cells.  相似文献   

19.
Omega-3 fatty acids and anorexia   总被引:2,自引:0,他引:2  
PURPOSE OF REVIEW: To review the mechanisms of action of omega-3 fatty acids and their role in the brain, as well as their therapeutic implications in anorexia. RECENT FINDINGS: Recent studies have demonstrated that omega-3 fatty acids modulate changes in the concentrations and actions of several orexigenic and anorexigenic neuropeptides in the brain, including neuropeptide Y, alpha-melanocyte stimulating hormone and the neurotransmitters serotonin and dopamine. In patients with acute and chronic inflammatory conditions, low tissue concentrations of omega-3 fatty acids and high concentrations of proinflammatory cytokines are found, in association with anorexia and decreased food intake. The data suggest that omega-3 fatty acid supplementation suppresses proinflammatory cytokine production and improves food intake by normalizing hypothalamic orexigenic peptides and neurotransmitters. SUMMARY: Based on current data, omega-3 fatty acid supplementation has a role in the treatment of anorexia by stimulating the production and release of orexigenic neurotransmitters in food intake regulatory nuclei in the hypothalamus.  相似文献   

20.
Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.  相似文献   

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