预防性给予葡多酚对小鼠血栓形成的影响

目的观察预防性给予葡多酚(GPC)对小鼠血栓形成的影响。方法将昆明种小鼠随机分为5组,分别给予不同剂量GPC、阿斯匹林或生理盐水8d,期间在实验的第6d除正常对照组外,所有动物经皮下注射1%角叉菜胶诱发血栓形成,第9d测定小鼠尾部血栓形成状况,并用放射免疫法检测血浆α-颗粒膜蛋白(GMP140)和血栓素B2(TXB2)的含量。结果高剂量GPC组小鼠血栓绝对长度、GMP140和TXB2含量分别为(12.250±0.121)mm、(7.47±0.69)ng/ml和(195.59±35.83)pg/ml,均低于血栓对照组,差别有统计学意义(P<0.05)。结论GPC对角叉菜胶诱发的小鼠血栓形成及血小板活化有一定的预防作用。     

葡多酚对大鼠DNA氧化损伤的防护作用研究

目的:研究葡多酚(GPC)对DNA氧化损伤防护作用。方法: 将大鼠分为正常对照组、高脂膳食、高脂+乙醇、高脂+ GPC(50 mg/kg bw)、高脂+乙醇+ GPC(50 和100 mg/kg bw)等共6组,饲养6 w,处死动物,制作脾细胞悬液,分不给和给予Fenton氧化两种处理,测定脾细胞DNA损伤程度及血清MDA水平和SOD活力等指标。结果: 1.不给予Fenton氧化处理的高脂+乙醇组和高脂+乙醇+GPC(100 mg/kg bw)组的 DNA损伤程度分别为76.15%和15.27%,给予氧化处理的为83.02%和19.83%,差异均有显著意义。2.高脂+乙醇组和高脂+乙醇+GPC(100 mg/kg bw)组的MDA分别为8.18±0.98 mmol/L和5.63±1.16 mmol/L,SOD为597.04±88.88 NU/ml和729.71±88.88 NU/ml,差异均有显著意义。结论: GPC对高脂和乙醇引发的DNA氧化损伤有防护作用。     

葡多酚对肝细胞内Ca~(2+)浓度和增殖活性的影响

目的探讨葡多酚(GPC)对正常肝细胞和受乙醇损伤肝细胞内Ca2+浓度与细胞增殖活性的影响。方法将大鼠正常肝细胞和乙醇损伤肝细胞加入不同剂量GPC共同培养,用Fura-2荧光测定肝细胞内Ca2+浓度,用MTT法测定细胞增殖活性。结果①正常对照组和乙醇对照组的Ca2+浓度分别为(108·26±14·17)和(651·24±47·95)nmol/L,二者差异有显著性意义(P<0·05);中、高剂量GPC组均较乙醇对照组显著性降低(P<0·05)。②加入GPC的正常肝细胞内Ca2+浓度依次为:细胞外液含Ca2+组>外液无Ca2+组>正常对照组。③正常肝细胞和乙醇损伤肝细胞的中、高剂量GPC组细胞增殖活性均较正常对照组和乙醇对照组显著性升高(P<0·05)。结论GPC可通过增加细胞外液Ca2+内流和胞内Ca2+库的释放两种途径升高正常肝细胞内Ca2+浓度,提高细胞增殖活性,并可抑制乙醇引发的肝细胞内Ca2+浓度异常升高(超载)和细胞增殖活性损伤。     

葡多酚对外周血淋巴细胞辐射损伤的保护作用

目的研究葡多酚(GPC)对人外周血淋巴细胞辐射损伤的保护作用。方法取14名健康女性的外周血,用直线加速器X射线一次性照射。设高、低剂量GPC组、阳性对照和阴性对照组,分别在培养24、48、72h后检测淋巴细胞凋亡率、增殖活性和淋巴细胞转化率等指标。结果照射后48h,阳性对照组的淋巴细胞凋亡率和增殖活性分别为(45.19±4.80)%和0.66±0.03;高剂量GPC组则为(36.26±6.77)%和0.86±0.05,差别有统计学意义(P<0.001)。结论GPC可降低X射线对淋巴细胞损伤的程度,对淋巴细胞辐射损伤有良好防护作用。     

葡多酚对活性氧自由基的清除作用研究

目的 :　探讨葡多酚 ( GPC)对活性氧自由基的清除作用。方法 :　采用电子自旋共振 ( ESR)和自旋捕集技术直接测定不同浓度 GPC对 Fenton反应体系产生的羟自由基 (· OH)、光照核黄素 /EDTA体系产生的超氧阴离子 ( O·2 )及 Fe2 + 启动线粒体膜脂质过氧化产生的脂类自由基 ( LOO· )清除作用。结果 :　 GPC浓度为 1 mg/L、1 0 mg/L、1 0 0 mg/L、1 0 0 0 mg/L对·OH的清除率 ( % )依次为 9.0、2 0 .6、47.7、57.7,对 O·2 的清除率 ( % )分别为 1 0 .9、1 7.0、50 .9、72 .1 ,对LOO·的清除率 ( % )依次为 39.8、49.6、65.9、71 .4。葡多酚对· OH、O·2 及 LOO· 50 %的清除浓度 ( IC50 值 )分别为 1 2 8.9mg/L、89.4mg/L、1 0 .4mg/L。结论 :　葡多酚对三种活性氧自由基均有不同程度的清除作用 ,其中 LOO· >O·2 >· OH。     

葡多酚对大鼠肝脏TNF-α与TGF-β_1mRNA异常表达的抑制作用

目的: 研究葡多酚(GPC)对N-亚硝基化合物引发的大鼠肝细胞肿瘤坏死因子α(TNF-α)mRNA与转化生长因子β1(TGF-β1)mRNA异常表达的抑制作用。 方法:将大鼠随机分为正常对照组、阳性对照组和2个GPC实验组,每组10只,雌雄各半。后3组给口服50 mg/kg bw亚硝酸钠诱发突变,2个GPC实验组经口分别给予GPC100 mg/kg bw和10 mg/kg bw,喂养8 w,体内灌注固定肝组织,用原位杂交技术检测肝细胞TNF-αmRNA与TGF-β1 mRNA的表达水平。 结果: 阳性对照组TNF-αmRNA与TGF-β1 mRNA表达的阳性细胞率分别为30.23%和19.47 %,高剂量GPC组则为11.94 %和6.96 %,低剂量GPC组分别为18.16%和14.03%,与阳性对照组之间的差别均有显著性意义(P<0.05)。结论: 葡多酚对N-亚硝基化合物引发的大鼠肝细胞TNF-αmRNA与TGF-β1 mRNA的异常表达均有抑制作用。     

共轭亚油酸对肥胖大鼠脂联素基因表达的影响

目的研究共轭亚油酸对饮食诱导肥胖大鼠脂联素基因表达的影响。方法选用雄性Wistar大鼠,随机分为对照组、高脂组、高脂+共轭亚油酸组(每100g饲料含共轭亚油酸分别为075g、150g、300g),每组动物10只,观察共轭亚油酸对肥胖大鼠胰岛素、血糖水平的影响,并应用RTPCR的方法检测脂联素、过氧化物酶体增殖物活性受体γ(PPARγ)的表达水平。结果高脂组大鼠血清胰岛素和血糖水平分别为(1111±273)μIU/ml,(509±066)mmol/L,075%、150%、300%剂量组胰岛素水平分别为(699±177)μIU/ml,(736±148)μIU/ml,(785±160)μIU/ml,血糖水平分别为(428±072)mmol/L,(418±055)mmol/L,(406±063)mmol/L,且共轭亚油酸可增加肥胖大鼠脂肪组织脂联素、PPARγmRNA的表达水平。结论共轭亚油酸可通过激活PPARγ上调脂联素基因的表达,改善肥胖大鼠的胰岛素抵抗。     

葡多酚对乳腺癌细胞P38MAPK信号传导通路的影响

目的:探讨葡多酚(grape proanthocyanidins,GPC)对P38MAPK(P38 mitogen-activated protein kinase,P38 MAPK)信号转导通路的影响。方法:将接种EMT-6乳腺癌细胞的BALB/C小鼠分别经口灌胃给予10、100、200mg/kg bw GPC,连续2w。用Western blot方法检测肿瘤组织磷酸化P38MAPK蛋白和MMP-2蛋白的表达水平。结果:肿瘤对照组和200mg/kgGPC组的磷酸化P38MAPK蛋白表达水平(相对灰度值)分别为1.16±0.18和0.58±0.12,MMP-2蛋白表达水平分别为0.98±0.04和0.69±0.04,差别均有显著性意义(P<0.05)。结论:GPC对乳腺癌P38MAPK信号转导通路的活化和MMP-2蛋白的表达均有一定抑制作用。     

葡多酚对血管内皮细胞自由基损伤的影响

目的:探讨葡多酚(grape procyanidin,GPC)对血管内皮细胞氧自由基损伤的保护作用。方法:取静脉内皮细胞株ECV304在含有不同浓度GPC的培养液中培养,用Fenton试剂引发细胞氧自由基损伤,分别于培养12,24,36和48h采用MTT法测定细胞的增殖水平、用流式细胞法测定细胞凋亡和MDA含量等指标。结果:培养12h阳性对照组及低、高剂量GPC组细胞增殖活性分别为0.475±0.122、0.524±0.068和0.949±0.111,差别均有显著性意义(P<0.05),24h细胞凋亡率分别为12.63%,10.17%和5.45%。结论:GPC可有效抑制氧自由基引发的细胞增殖活性损伤与细胞凋亡,对防止内皮细胞氧化损伤有很好的作用。     

中链脂肪酸对营养性肥胖大鼠体重及脂质代谢的作用

目的研究中链脂肪酸(MCFA)对营养性肥胖大鼠体重、体脂和血脂水平的影响。方法采用预防肥胖模型法,每天给予SD大鼠高脂营养饲料,并灌胃含不同剂量MCFA的食用油脂,饲养38天,观察体重、摄食量、体脂重量、血脂、胰岛素水平在不同剂量组动物间的差异。结果高、中、低三个剂量组大鼠分别摄入0·975、0·325和0·163g/kg bw MCFA38天,高剂量组与模型对照组相比,体重明显较低[分别(295·2±29·7)g和(324·6±9·1)g](P<0·05),脂肪垫重量明显较轻[分别(5·30±1·57)g和(7·20±1·74)g](P<0·05),脂肪细胞明显较小;各剂量组总的摄食量不显著低于模型对照组;血清甘油三酯(TG)、总胆固醇(TC)、胰岛素水平与模型对照组比较差异无显著性,中、高剂量组高密度脂蛋白胆固醇(HDL-C)水平高于模型对照组[分别(0·71±0·11)mmol/L、(0·73±0·12)mmol/L、(0·60±0·06)mmol/L](P<0·05),高剂量组大鼠的瘦素水平显著低于模型对照组[分别(1·61±0·39)ng/ml和(2·04±0·46)ng/ml](P<0·05)。结论在饲料摄入量没有差别的前提下,摄入0·975g/kg bw MCFA对营养性肥胖大鼠的体重增长有一定抑制作用,对血脂水平没有不良影响。     

镁预防高脂膳家兔内皮细胞损伤的研究

目的：通过血浆血栓素（ＴＸＢ２）、６－酮前列腺素Ｆ１α（６－Ｋｅｔｏ－ＰＧＦ１α）、内皮素（ＥＴ）及一氧化氮（ＮＯ）等几个方面探讨镁预防高脂膳家兔诱发动脉粥样硬化形成的可能作用。方法：成年新西兰家兔随机分为正常对照组（基础饲料＋普通饮水）,高脂对照组（高脂饲料＋普通饮水）,高镁组（高脂饲料＋含镁４２．１ｍｇ／ｋｇ饮水）,观察１２周。结果：高脂对照组家兔血浆前列腺素Ｆ１α水平及ＮＯ含量下降,ＴＸＢ２及ＥＴ水平上升。补镁提高血浆６－Ｋｅｔｏ－ＰＧＦ１α浓度和ＮＯ含量,同时也可明显降低家兔血浆ＴＸＢ２、ＥＴ及ＴＸＢ２／６－Ｋｅｔｏ－ＰＧＦ１α比值。结论：镁有调节花生四烯酸代谢、保护内皮细胞及防治动脉粥样硬化形成的作用。     

Subject Index to Volume 27

Growing male rats that weighed 120 ± 5 g were kept for 30 days on the following synthetic diets: high protein diet (HPD), 59% casein; high fat diet (HFD), 50% saturated fat; and normal diet (ND), 19% casein, 10% saturated fat, and 60% sucrose. Other essential dietary ingredients were included in all the diets. All animals were injected at the end of the 30–day period with parathion [10 mg/kg intraperitoneal (ip) injection as a single dose] or dichlorvos (30 mg/kg ip as a single dose) to compare the effect of dietary pretreatments on mortality from parathion and dichlorvos. A lower dose of parathion (7.5 mg/kg) and dichlorvos (20 mg/kg) was employed in another set of experiments to compare the spontaneous regeneration of plasma and red blood cell (RBC) cholinesterase (ChE) activity at 2 hr, 1 day, 3 days, and 5 days after administration of parathion or dichlorvos. The effect of these diets on hepatic microsomal oxidases was also determined. Results showed that diets per se did not affect initial plasma and RBC ChE activity. The HPD and HFD significantly protected against mortality from parathion but not from dichlorvos. Hepatic microsomal cytochrome P–450 and aminopyrine demethylase activity were unchanged, but aniline hydroxylase activity was increased significantly by HPD and HFD. Parathion oxidase in hepatic microsomes was significantly increased in rats fed HFD only. For the HPD, spontaneous regeneration of ChE diminished in RBCs in parathion-intoxicated rats and in plasma and RBCs of dichlorvos-intoxicated rats. The HFD did not affect ChE regeneration in plasma or RCBs of parathion-intoxicated rats, but significantly increased it in dichlorvos-intoxicated rats. There may be a reversible protein sequestration of both insecticides in growing rats fed HPD.     

葡多酚对高脂膳大鼠血脂与脂质过氧化的影向

目的　观察葡多酚 (GPC)对饲以高脂膳食、乙醇等不同膳食的大鼠血脂及脂质过氧化的影响。方法　将大鼠随机分为正常对照组、高脂膳组、高脂乙醇组、高脂GPC组、高脂乙醇GPC(高、低剂量 )组、高脂乙醇VE组 7个组 ,喂养 6周 ,测定血清甘油三脂 (TG)、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL -C)、低密度脂蛋白胆固醇 (LDL -C)、活性氧 (ROS)、丙二醛 (MDA)水平及超氧化物歧化酶 (SOD)活性等指标。结果　高脂组、高脂乙醇组的血清TG、TC、ROS、MDA水平均较实验前显著性升高 ;同高脂乙醇组比较 ,高脂乙醇高GPC组的血清TC、MDA水平均显著性降低 ,SOD活性显著性升高 (P <0 0 5 )。结论　GPC对乙醇与高脂膳食引起的血脂水平升高和脂质过氧化均有一定的抑制作用。     

硒和/或维生素E预防大鼠内皮细胞损伤的实验研究

用含硒（Ｓｅ０．５ｍｇ／ｋｇ）和／或维生素Ｅ（ＶＥ０．６ｇ／ｋｇ）的高脂饲料喂养成年雄性Ｗｉｓｔａｒ大鼠１２周。结果：高脂对照组大鼠血浆前列腺素Ｆｌα（６－酮－ＰＧＦ１α）水平下降，而血清脂质过氧化物（ＬＰＯ）、血浆血栓素（ＴＸＢ２）及内皮素（ＥＴ）水平上升；补Ｓｅ、ＶＥ及Ｓｅ＋ＶＥ可明显降低大鼠血清ＬＰＯ、血浆ＴＸＢ２、ＥＴ及ＴＸＢ２／６－酮－ＰＧＦ１α比值。同时，除了明显提高血浆谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活力外，血浆６－酮－ＰＧＦ１α浓度明显升高。实验提示，Ｓｅ和／或ＶＥ有调节花生四烯酸代谢及保护内皮细胞的作用。     

急性心肌梗死患者治疗前后血浆ET-1、血清6-酮-PGF1α、TXB2和GMP-140水平检测的临床意义

目的 探讨急性心肌梗死患者治疗前后血浆ET-1、血清6-酮-PGF1α、TXB2和GMP-140水平的变化及临床意义.方法 应用放射免疫分析法对33例急性心肌梗死患者治疗前后进行了血浆ET-1、血清6-酮-PGF1α、TXB2和GMP-140水平测定,并与35名正常人作比较.结果 急性心肌梗死患者在治疗前后血浆ET-1、TXB2和GMP-140水平非常显著地高于正常人组（P＜0.01）,而血清6-酮-PGF1α水平又明显低于正常人组（P＜0.05）,经治疗1个月后与正常人比较仍有差异（P＜0.05）.血浆ET-1水平和TXB2、GMP-140水平呈正相关（r=0.4986,0.5014,P＜0.05）,6-酮-PGF1α水平呈负相关（r=-0.4712,P＜0.05）.结论 测定急性心肌梗死患者治疗前后血浆ET-1、血清6-酮-PGF1α、TXB2和GMP-140水平变化对观察病情和预后判定具有重要的临床价值.     

High-fat diet feeding elevates skeletal muscle uncoupling protein 3 levels but not its activity in rats

OBJECTIVE: The objective of this study is to test the impact of high-fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole-body energy homeostasis. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low-fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty-four-hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability. RESULTS: Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2-fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low-fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24-hour energy expenditure. DISCUSSION: The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24-hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3-mediated uncoupling activity.     

细胞因子信号转导抑制因子3基因沉默对高脂喂养肥胖幼年大鼠的影响

目的 观察RNA干扰(RNA interference, RNAi)沉默细胞因子信号转导抑制因子3(suppressor of cytokine signaling3, SOCS3)能否改善高脂喂养幼年大鼠的肥胖和瘦素抵抗。方法 32只5周龄健康雄性SD大鼠, 随机分为4组干扰+普食组, 对照+普食组, 干扰+高脂组, 对照+高脂组, 每组各8只。侧脑室注射慢病毒载体SOCS3干扰液或慢病毒载体对照液, 然后给予高脂或普通饲料喂养28 d, 期间测摄食量和体重。处死后取血, 放射免疫法测瘦素(leptin)含量, 全自动生化分析仪测血糖(plasma glucose, PG)、总胆固醇(total cholesterol, TC)、甘油三脂(triglycerides, TG)水平。结果 干扰+高脂组大鼠的摄食量和体重分别于注射后第14天和第21天起低于对照+高脂组(P＜0.05);于注射后第22天起和第28天高于对照+普食组(P＜0.05)。干扰+高脂组大鼠瘦素水平(0.86±0.12)ng/mL低于对照+高脂组(0.97±0.13)ng/mL, 高于对照+普食组(0.75±0.10)ng/mL(P＜0.05)。结论 SOCS3基因沉默可改善幼年大鼠高脂喂养诱导的肥胖和瘦素抵抗。     

维生素E、C联用对老年正常血脂冠心病氧化修饰低密度脂蛋白及血小板活化状态的影响

目的：探讨老年正常血脂冠心病患者体内低密度脂蛋白（ＬＤＬ）氧化修饰状态,及氧化修饰低密度蛋白（Ｏｘ－ＬＤＬ）与血小板活化状态的关系。方法：选择心病组和正常组各２６全色Ｏｘ－ＬＤＬ、血小板膜α－颗粒膜蛋白（ＧＭＰ－１４０）、血栓素Ｂ２（ＴＸＢ２）为指标,在冠心病组服用维生素Ｅ、Ｃ前及一个月后比较上述各指标的变化。结果：实验发现,正常血脂老年冠心病组血浆Ｏｘ－ＬＤＬ、ＴＸＢ２浓度,ＧＭＰ－１４０水平较     

Consumption of a high-fat diet containing lard during the growth period in rats predisposes them to favorably respond to the diet in later life

To investigate whether preferential fat intake by adult rats could be linked to fat-feeding of rats during the growth period, this paper describes the next two studies. Three groups of 4-wk-old male rats in study 1 received one of three diets: control diet (CTD), low-fat high-carbohydrate diet (LFD), and high-fat low-carbohydrate diet (HFD). After 6 wk (dietary treatment period), 6 rats in each of the groups were sacrificed and the remaining rats were placed on a self-selection regimen of fat-protein diet (FPD) and carbohydrate-protein diet (CPD) for 3 wk (self-selection period). After the dietary treatment period, liver weight and plasma insulin concentration of the LFD group and perirenal fat tissue weight and plasma triacylglycerol and leptin concentrations of the HFD group were higher than those of the CTD group. Although no significant difference in fat energy ratio (F ratio) of combination diets self-selected by the three groups was observed, the F ratios of the combination diets were higher than that of the CTD. After the self-selection period, liver weight and plasma insulin concentration of the LFD group and plasma triacylglycerol concentrations of the HFD group decreased. These data suggested that the dietary selection pattern of the rats was associated with a reduced basal plasma insulin concentration. Three groups of rats in study 2 were placed on a self-selection regimen of the LFD and the HFD after being fed one of three diets (LFD, CTD and HFD) for 6 wk. Although the F ratio of the combination diet consumed by the CTD and the LFD groups was similar to that of the combination diet consumed by rats in study 1, the F ratio of the combination diet consumed by the HFD group was higher than that of other groups. These findings suggest that consumption of the fatty food during the growth period predisposed them to favorably respond to the diet that had become familiar to them in later life.