073 n-3脂肪酸对肿瘤细胞凋亡的影响及作用机制

n-3脂肪酸(n-3 PUFA)是一类重要的多不饱和脂肪酸,与人体多种生理过程密切相关.目前研究发现它们可能具有一定的抗肿瘤效应,而经多种途径调控肿瘤细胞凋亡是其发挥作用的重要机制之一.本文从分子生物学角度就n-3 PUFA对肿瘤细胞凋亡的影响及作用机制作一综述.     

n-3多不饱和脂肪酸对老年人肌肉衰减影响的研究进展

老年人的肌肉衰减与衰老相关的慢性炎症密切相关.n-3多不饱和脂肪酸(polyunsaturated fatty acids,PUFAs)具有抗炎特性,可能有利于减缓老年人的肌肉衰减进程.近年部分临床研究结果显示,大剂量补充n-3 PUFAs能够增加老年人(尤其是女性)肌肉质量、提高肌肉力量或改善肌肉功能,其机制可能与下...     

n-3多不饱和脂肪酸逆转肿瘤耐药性的研究进展

肿瘤细胞耐药的产生是导致肿瘤病人药物治疗失败的主要原因.研究表明,n-3多不饱和脂肪酸(n-3PUFA)能增加肿瘤细胞对化疗药物的敏感性,从而逆转肿瘤细胞对化疗药物的耐药性.这种作用可能通过脂质过氧化作用、诱导细胞凋亡、影响化疗药物的分布、抑制肿瘤新生血管和调节相关信号通路等机制来提高肿瘤细胞对化疗药物的敏感性.     

高n-3多不饱和脂肪酸鱼油饮食对小鼠肠道菌群的影响

目的探讨高n-3多不饱和脂肪酸(n-3 PUFAs)鱼油饮食的摄入对于肠道菌群的影响。方法选取成年C57BL/6小鼠,随机分成正常对照低脂组和高n-3多不饱和脂肪酸鱼油饮食两组,进行为期4w的低脂(low fat diet,LFD)和鱼油饮食(fish oil diet,FO)。并于第4w末收集粪便,提取基因组DNA,使用Miseq高通量测序技术分析其菌群结构特征。结果 FO组和LFD组小鼠肠道内菌群差异明显。FO组菌群多样性较LFD组降低,同时Bacteroidetes(拟杆菌门)明显下降,出现了新的优势菌群Akkermansia菌属。结论高n-3多不饱和脂肪酸鱼油饮食的摄入明显改变了小鼠肠道菌群结构,而这有可能是n-3PUFA在体内调控机体免疫功能的机制之一。     

父代n-3多不饱和脂肪酸对子代小鼠端粒长度的影响

目的 探讨父代备孕期n-3多不饱和脂肪酸(n-3 PUFAs)对子代端粒长度(TL)的影响。方法 将3～4周龄C57BL/6J雄性小鼠(父代)随机分为3组(10只/组),分别给予n-3 PUFAs缺乏(n-3 D)、n-3 PUFAs正常含量(n-3 N)和n-3 PUFAs高含量(n-3 H)饲料饲喂12周，然后与12周龄正常体重的同品系雌性小鼠交配繁育子代小鼠。对成年期子代小鼠进行外周血和组织TL以及端粒酶和端粒结合蛋白基因mRNA表达检测。结果 与n-3 N饲料相比，父代n-3 D饲料喂养使得子代雌和雄性小鼠的外周血、肝脏、脂肪组织和/或脑组织中的TL显著缩短，伴随雄性肝脏端粒酶组分TERC以及结合蛋白TRF2和POT1a的mRNA表达下调；同时显著缩短了子代睾丸TL并下调了端粒酶(TERT)和结合蛋白(TRF1、TRF2、POT1a)的mRNA表达。父代n-3 H饲料喂养虽然未改变子代的TL和肝脏端粒酶及结合蛋白表达，但却显著逆转了n-3 D饲料的不良影响。另外，相对于n-3 N饲料，父代n-3 D和n-3 H饲料喂养均未改变自身睾丸TL,但n-3 H饲料喂养时睾丸TL以及端粒...     

不同n-3/n-6多不饱和脂肪酸构成比膳食对大鼠一磷酸腺苷活化蛋白激酶表达的影响

目的研究不同n-3/n-6配比脂肪酸对大鼠磷酸腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)蛋白及活性表达的影响。方法58只SD大鼠适应性喂养7d后,尾静脉取血。根据血清总胆固醇水平随机分为:空白(基础饲料);高脂(高脂饲料);高脂1:1(高脂饲料+n-3/n-6=1:1配方油);高脂1:5(高脂饲料+n3/n6=1:5配方油);低脂1:1(脱脂基础饲料+n-3/n-6=1:1配方油);低脂1:5(脱脂基础饲料+n3/n6=1:5配方油)6组,喂养45d,观察大鼠摄食与体重增长。于实验前1d,15d,30d,45d分别各取血测血清总胆固醇水平,于D45处死动物。Western blotting分别分析肝和下丘脑组织中AMPK-α总蛋白及其活性表达。结果添加PUFA的4个比例组血清TC、体重与高脂组相比,显著降低,且低脂2个比例组和高脂1:1组均与高脂1:5组相比有显著差异。添加PUFA的4个比例组均与高脂组相比,大鼠下丘脑AMPK-α总蛋白表达水平明显降低,肝AMPK-α蛋白表达水平均比高脂组明显升高。结论PUFA改善血脂可能是通过增加肝AMPK表达,抑制下丘脑AMPK表达,增加肝脂肪酸氧化和抑制食欲,影响血脂代谢。     

硒与n-3多不饱和脂肪酸对甲基汞神经毒性影响的研究进展

水产品是人类甲基汞暴露的来源之一,同时包含多种对神经系统发育有重要作用的营养物质,如硒、n-3多不饱和脂肪酸。目前,多项研究提示硒与n-3多不饱和脂肪酸对甲基汞神经毒性可能具有潜在的保护作用。本文回顾了硒与n-3多不饱和脂肪酸对甲基汞神经毒性影响的流行病学与实验研究,重点讨论了其与甲基汞可能的相互作用及作用机制,在此基础上对未来的研究方向进行展望。     

n-3多不饱和脂肪酸对肥胖小鼠肠道菌群的影响

目的 探讨n-3多不饱和脂肪酸(n-3 polyunsaturated fatty acids,n-3 PUFAs)对饮食诱导肥胖小鼠肠道菌群的影响。方法 将30只3～4 周龄C57BL/ 6J雄性小鼠,随机分为3组(10只/组),分别给予高脂饲料、鱼油n-3 PUFAs高脂饲料(脂肪含量均为34.9%,供能比均为60%)以及正常脂饲料(脂肪来源于猪油和葵花籽油,脂肪含量为4.3%,供能比为10%)喂养16周。然后采集粪便,采用16sDNA-实时荧光定量PCR方法检测肠道菌群变化;取结肠组织,采用实时荧光定量PCR方法检测白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)以及单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)的mRNA表达水平。结果 与正常脂饲料喂养对照组小鼠相比,高脂饲料诱导肥胖小鼠粪便中厚壁菌门及乳杆菌属的数量显著增多,而拟杆菌门、放线菌门、变形菌门以及双歧杆菌属的数量则显著减少(P<0.05)。两组肥胖小鼠相比,鱼油n-3 PUFAs高脂组肥胖小鼠的粪便双歧杆菌属数量明显增加,而乳杆菌属数量显著减少(P<0.05)。对结肠炎性因子mRNA表达水平检测显示,高脂饲料组肥胖小鼠的IL-1β、IL-6、TNF-α及MCP-1表达量较正常脂饲料组小鼠均明显升高(P<0.05),而IL-10的表达量无变化;鱼油n-3 PUFAs高脂饲料组肥胖小鼠的IL-1β、TNF-α较高脂饲料组肥胖小鼠有显著性的降低(P<0.05)。结论 鱼油n-3 PUFAs可以改善肥胖状态下的肠道菌群紊乱及肠道炎症状态。     

n-3多不饱和脂肪酸对小鼠非酒精性脂肪肝的预防作用

目的以EPA三甘油三酯(triEPA)和DHA三甘油三酯(triDHA)为材料,研究其对非酒精性脂肪肝(NAFLD)模型小鼠的预防与改善作用。方法 C57BL/6J雄性小鼠40只,按体重随机分为对照组、triEPA补充组、triDHA补充组、模型组,每组10只小鼠。除对照组喂正常饲料外,其余各组都喂以高脂饲料,triEPA和triDHA补充组每天以1000 mg/kg bw的triEPA和triDHA乳化液灌胃,对照组和模型组每日以等量的5%阿拉伯胶溶液灌胃,饲养8w后处死小鼠,收集血液和肝脏标本。采用HE染色法观察肝脏的病变情况并测定血清谷丙转移酶(ALT)、谷草转氨酶(AST)、总甘油三酯(TG)、总胆固醇(TC)和肝脏TG、TC。结果高脂饲料诱导引起小鼠肝脏脂肪性变,triEPA和triDHA补充高脂饲料诱导的NAFLD模型小鼠8w后,显著降低了小鼠的肝重系数、血清ALT和AST活性,降低了肝脏TG和TC水平,显著降低肝脏的脂变程度。结论 triEPA和triDHA对小鼠NAFLD有积极的预防和改善作用。     

富含n-3多不饱和脂肪酸的肠外营养对脓毒症大鼠T淋巴细胞亚群和炎性因子的影响

目的:探讨富含n-3多不饱和脂肪酸(PUFA)的肠外营养(PN)对脓毒症大鼠外周血T淋巴细胞亚群和血清炎性因子的影响。方法:将36只大鼠随机分为四组,颈静脉置管术2 d后行盲肠结扎穿孔术或假手术,1对照组:给予自由饮食;2NS组:给予等渗盐水输注+自由饮食;3SO组:给予富含豆油的标准肠外营养(PN)液;4FO组:给予富含PUFA的PN液。脓毒症5 d后,检测IL-6、IL-10和T细胞亚群等。结果:脓毒症5 d后,FO组大鼠外周血CD3+、CD4+、CD4+/CD8+与NS组和SO组比有所升高,但较对照组大鼠下降;与NS组大鼠比,FO组血清IL-6、IL-10、外周血Tregs比例有所下降。结论:应用富含n-3 PUFA的PN可降低脓毒症大鼠血清炎性因子和调控外周血T淋巴细胞亚群。     

外周血淋巴细胞穿孔素和颗粒酶B在诊断移植肾急性排斥反应中的应用

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。     

外周血淋巴细胞穿孔素和颗粒酶B在诊断移植肾急性排斥反应中的应用

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穿孔索和颗粒酶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穿孔棠和颗粒酶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。     

膳食n-6/n-3脂肪酸比值对小鼠淋巴细胞脂肪酸构成和功能的影响

目的观察膳食n6n3脂肪酸比值对淋巴细胞脂肪酸构成及细胞功能的影响。方法BALBc小鼠随机分为5组n6n3比值分别为1(A组)、75(B组)、15(C组)、30(D组)和正常对照组,其中实验组S∶M∶P模拟中国居民膳食脂肪酸摄入的S∶M∶P为1∶15∶1,正常对照组为AIN93G配方的1∶15∶37。基础饲料采用AIN93G配方,脂肪酸构成以食用油脂调配。饲养12周。测定小鼠T淋巴细胞功能,脾淋巴细胞脂肪酸构成、PGE2水平。结果n6n3比值接近1时,小鼠T淋巴细胞增殖活性、CD4+、CD8+T细胞比例、培养上清IL2、PGE2水平显著降低;淋巴细胞C18∶2、C20∶4、n6PUFA含量显著减少;C22∶6、C16∶1、C18∶1、总MUFA含量明显高于其他实验组。淋巴细胞C22∶6含量与淋巴细胞增殖活性显著负相关;C20∶5含量与CD4+T淋巴细胞比例、IL2水平显著负相关;C16∶1含量与CD4+、CD8+T淋巴细胞比例显著负相关。结论小鼠脾淋巴细胞的脂肪酸构成受膳食脂肪酸构成的影响;n6n3比值为1组与比值为30的膳食组相比较,小鼠T淋巴细胞增殖活性受到抑制。     

Maternal Supplementation with Cow’s Milk Naturally Enriched with PUFA Alters the Metabolism of Sows and the Fatty Acid Profile of the Offspring

The study aimed to evaluate the supplementation of gilts with cow’s milk naturally enriched with n-3 and n-6 polyunsaturated fatty acids (PUFA) on reproductive outcomes, and the serum biochemical and FA profile of swine females and their offspring. During 316 days, 30 gilts were distributed into three groups: (1) Control, fed a basal diet + milk from cows without oil; (2) n-3, fed a basal diet + milk from cows fed a diet enriched with linseed oil; (3) n-6, fed a basal diet + milk from cows fed a diet enriched with soybean oil. The gilts receiving the diets containing PUFA had higher serum urea and very-low-density lipoprotein levels and lower serum total protein and low-density lipoprotein levels compared to the Control group. Females supplemented with n-3 presented higher serum palmitic acid and γ-linolenic acid levels than those fed n-6. Piglets from the Control group were heavier at birth than those from females supplemented with enriched milk. The piglets from females receiving enriched milk had 140 g higher body weight from 1 to 21 days old compared to the Control group, and greater average daily weight gain from 7 to 14 days old. The serum eicosapentaenoic acid level of piglets fed n-3 was 69% higher than those fed n-6, which reduced the AA/EPA ratio. Gilts supplemented with PUFA-enriched cow’s milk showed changes in their serum palmitic and γ-linolenic acid levels, in addition to improved performance, EPA concentration and consequently reduced AA/EPA ratio in their piglets, demonstrating beneficial results for their progeny.     

n-6/n-3脂肪酸配方油对大鼠血脂和脂质过氧化的影响

目的研究不同脂肪酸n-6/n-3组成的配方油对大鼠血脂和脂质过氧化的影响.方法成年SD雄性大鼠喂饲含相同胆固醇(0.5%,W/W)、饱和脂肪酸(占供给能量10%)、单不饱和脂肪酸(占供给能量13%)和多不饱和脂肪酸(占供给能量12%),但不同脂肪酸n-6/n-3比(6.48、2.07、0.93、031)的4种配方油的高脂合成饲料60天,观察大鼠血脂及脂质过氧化的变化.结果4种配方油比猪油均显著降低血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、LDL-C/HDL-C、AI[(TC-HDL-C/HDL-C,致动脉粥样硬化指数)],升高HDL-C/TC;配方油D具有独特的升高血清HDL-C2的作用;配方油A、C、D显著降低血清TG,而配方油B作用不明显.以n-3多不饱和脂肪酸占优势的配方油C、D比以n-6多不饱和脂肪酸占优势的配方油A、B显著地升高血清丙二醛,降低血清超氧化物歧化酶、全血谷胱甘肽过氧化物酶活性.4组配方油大鼠的心、脑脂褐质含量均比实验前增高,各配方油间无显著差异;心、脑脂褐质与血脂的相关分析发现心、脑脂褐质与血清TC、LDL-C呈正相关,与血清高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)关系不明显.结论从预防动脉粥样硬化的角度,脂肪酸n-6/n-3比在2.07～6.48范围内是合理的脂肪酸供给模式.     

不同n-6/n-3多不饱和脂肪酸构成比对高脂饲料喂养大鼠脂联素和糖脂代谢及抗氧化能力的影响

目的探讨高脂饲料喂养条件下,不同n-6/n-3多不饱和脂肪酸(polyunsaturated fatty acid,PUFA)构成比对大鼠脂联素和糖脂代谢及抗氧化能力的影响。方法50只雄性Wistar大鼠按体重随机分为5组:1个普通饲料组(脂肪供能比17%,n-6/n-3PUFA=5∶1)和4个高脂饲料组(脂肪供能比均为42%,n-6/n-3 PUFA构成比分别为1∶1、5∶1、10∶1、20∶1)。喂养12周后检测大鼠血糖和血脂(0、4、8和12周)、血清抗氧化指标(0和12周)以及睾周脂肪组织脂联素mRNA、蛋白表达和血清脂联素水平(12周)。结果大鼠各指标初始值组间差异均无统计学意义(P>0.05)。12周时,n-6/n-3PUFA 10∶1、20∶1组血糖显著高于对照组(P<0.05),4个高脂组血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)显著高于对照组(P<0.01),其中20∶1组TG显著高于其余3组(P<0.01);4个高脂组谷胱甘肽过氧化物酶和超氧化物歧化酶含量显著低于对照组(P<0.05),其中20∶1组下降最明显,丙二醛含量显著高于对照组(P<0.05),其中10∶1组上升最明显;20∶1组脂联素mRNA表达显著低于对照组、1∶1组和5∶1组(P<0.05),5∶1组脂联素蛋白表达水平显著高于其余高脂组(P<0.05),而20∶1组表达水平最低(P<0.05)。结论较低的n-6/n-3 PUFA构成比(1∶1和5∶1),有助于改善高脂饲料条件下大鼠糖脂代谢及抗氧化能力,提高脂联素表达。     

Effect of cholesterol feeding and sex difference on the tissue n-6 and n-3 fatty acid levels in fat-deficient rats treated with linoleate or linolenate

Weanling rats of both sexes fed on a fat-free diet for 8 weeks were given 5 i.p. Injections every 48 hr of 60 mg/100 g body weight of pure ethyl linoleate (LA) or linolenate (LN) with or without 1% dietary cholesterol supplementation. Phospholipid fatty acid compositions in plasma and liver were examined. LA administration increased n-6 fatty acids while LN treatment increased n-3 fatty acids. Cholesterol feeding significantly reduced 20: 4n-6 in LA treated animals and 20: 5n-3 and 22: 6n-3 in LN treated animals. The reductions in males were significantly greater than in females suggesting that the sex difference modulates the cholesterol-induced reduction of n-6 and n-3 fatty acids.     

Perturbation of phospholipid and triacylglycerol fatty acid positional location in the heart of rats depleted of n-3 long-chain polyunsaturates

Rats depleted of long-chain polyunsaturated n-3 fatty acids (n-3–D) display several features of the metabolic syndrome, including obesity, liver steatosis, insulin resistance, hypertension, and cardiac hypertrophy. In this study, the heart phospholipid (PL) and triacylglycerol (TG) fatty acid content and pattern were compared between female control rats (C) and n-3–D rats. The sole n-3 fatty acids found in n-3–D rats, C22:5(n-3) and C22:6(n-3), were 10 to 20 times lower than in C. The total fatty acid content of PL was lower in n-3–D rats than C. No ectopic TG accumulation was found in n-3–D rats. In both PL and TG, the C16:0/C16:1(n-7) and C18:0/C18:1(n-9) ratios suggested increased Δ9-desaturase activity in n-3–D rats. The PL C18:2(n-6)/C20:4(n-6) and C20:4(n-6)/C22:4(n-6) ratios were also lower in n-3–D rats than C. Prior intravenous injection of a medium-chain TG:fish oil emulsion to n-3–D rats 60 to 120 minutes before killing augmented the PL content in C22:5(n-3) and C22:6(n-3), minimized the age-related decrease in the PL C18:1(n-9) relative content, and increased the TG C22:4(n-6) content. The alteration of cardiac function in n-3–D rats and its improvement after injection of medium-chain TG:fish oil emulsion coincides with parallel changes in heart lipid fatty acid content and pattern.     

Lack of effect of dietary n-6:n-3 PUFA ratio on plasma lipids and markers of insulin responses in Indian Asians living in the UK

Summary Background Indian Asians living in Western Countries have an over 50 % increased risk of coronary heart disease (CHD) relative to their Caucasians counterparts. The atherogenic lipoprotein phenotype (ALP), which is more prevalent in this ethnic group, may in part explain the increased risk. A low dietary long chain n-3 fatty acid (LC n-3 PUFA) intake and a high dietary n-6 PUFA intake and n-6:n-3 PUFA ratio in Indian Asians have been proposed as contributors to the increased ALP incidence and CHD risk in this subgroup. Aim To examine the impact of dietary n-6:n-3 PUFA ratio on membrane fatty acid composition, blood lipid levels and markers of insulin sensitivity in Indian Asians living in the UK. Methods Twentynine males were assigned to either a moderate or high n-6:n-3 PUFA (9 or 16) diet for 6 weeks. Fasting blood samples were collected at baseline and 6 weeks for analysis of triglycerides, total-, LDL- and HDL-cholesterol, non-esterified fatty acids, glucose, insulin, markers of insulin sensitivity and C-reactive protein. Results Group mean saturated fatty acid, MUFA, n-6 PUFA and n-3 PUFA on the moderate and high n-6:n-3 PUFA diets were 26 g/d, 43 g/d, 15 g/d, 2 g/d and 25 g/d, 25 g/d, 28 g/d, 2 g/d respectively. A significantly lower total membrane n-3 PUFA and a trend towards lower EPA and DHA levels were observed following the high n-6:n-3 PUFA diet. However no significant effect of treatment on plasma lipids was evident. There was a trend towards a loss of insulin sensitivity on the high n-6:n- 3 PUFA diet, with the increase in fasting insulin (P = 0.04) and HOMA IR [(insulin x glucose)/ 22.5] (P = 0.02) reaching significance. Conclusion The results of the current study suggest that, within the context of a western diet, it is unlikely that dietary n-6:n-3 PUFA ratio has any major impact on the levels of LC n-3 PUFA in membrane phospholipids or have any major clinically relevant impact on insulin sensitivity and its associated dyslipidaemia. Source of support: This project was funded by the Food Standards Agency (FSA), UK.