共轭型亚油酸对B（a）P诱导小鼠前胃癌的抑制作用

目的 研究共轭型亚油酸(CAL)的抑癌作用,并为进一步探讨CLA的抑癌机制提供线索。方法 以B(a)P诱导建立小鼠前胃癌动物模型,观察CLA对小鼠前胃癌促长阶段的抑制效果,共分5组,即色拉油阴性对照组、CLA阴性对照组、B(a)P阳性对照组、B(a)P CLA高剂量实验组和B(a)P CLA低剂量实验组。整个实验期为23周,检测细胞增殖、Pan-ras P21蛋白表达和氧化还原酶等指标。结果 短期给予CLA对B(a)P诱导的小鼠前胃癌促长阶段具有明显的抑制作用,B(a)P阳性对照组、B(a)P CLA高剂量实验组和B(a)P CLA低剂量实验组的肿瘤发生率分别为100％、60％和69％。其抑癌机制与其对细胞增殖活力的抑制及对机体GSH-Px、GST和SOD酶活力的诱导作用有关,而并不依赖于对Pan-ras P21蛋白表达的调节途径。结论 提示共轭型亚油酸是一种很有前途的化学预防剂,其抑癌机制可能与影响机体氧化还原体系密切相关。     

共轭亚油酸抑制苯并(a)芘诱导小鼠前胃癌的研究

目的：探讨不同的构成的共轭亚油酸（CLA）对苯并（a)芘[B(a)P]诱导的小鼠前胃癌的抑制作用及可能机制。方法：用B(a)P在昆明种小鼠体内建立前胃癌模型,观察不同构成的CLA对小鼠前胃癌形成的抑制作用,同时采用蛋白印迹法分析小鼠前胃组织中的蛋白表达情况。结果：B(a)P组、75％纯度C9,T11-CAL组、98％纯度c9,t11-CAL组、98％纯度t10,c12-CLA组的前胃肿瘤发生率分别为100．0％、75．0％、69．2％、53．8％;蛋白印迹法分析结果表明,CAL抑制ERK－1的表达,促进MKP－1的表达,而对MEK－1的表达无明显影响,结论：不同构成的CAL对B(a)P诱导小鼠前胃癌均具有抑制作用;CAL影响MAPKs级联反应ERKs及此途径负调控子MKP－1蛋白的表达可能是其抑制肿瘤作用的机制之一。     

益生菌通过共轭亚油酸调节小鼠免疫功能

目的研究共轭亚油酸(CLA)益生菌嗜酸乳杆菌F0221对小鼠免疫调节能力的影响。方法 30只8w龄雄性昆种小鼠随机分为:空白对照、F0221(阴性对照I)、亚油酸(阴性对照II)、低剂量F0221+LA、高剂量F0221+LA5组。喂养4 w后,处死。采用气相色谱-质谱测定回肠和结肠内容物中c9,t11 CLA含量,利用ELISA试剂盒测定血清白介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)和前列腺素E2(PGE2)浓度,计算脾脏和胸腺指数,并测定脾淋巴细胞增殖能力和腹腔巨噬细胞吞噬能力。结果与空白对照组相比,高剂量F0221+LA组小鼠回肠和结肠内容物中c9,t11 CLA含量、血清IL-2、TNF-α和PGE2浓度、脾淋巴细胞增殖能力和腹腔巨噬细胞吞噬能力均显著提高,但两剂量组之间上述指标无显著性差异。结论嗜酸乳杆菌F0221在小鼠体内利用肠道中的亚油酸合成c9,t11 CLA,进而显著增强机体的特异性和非特异免疫能力,其调节机制可能是通过降低PGE2体内合成能力实现的。     

番茄红素对苯并(a)芘诱发小鼠前胃组织癌变的影响

目的观察番茄红素对苯并(a)芘[B(a)P]诱发小鼠前胃组织癌变过程的影响及其可能的作用机制。方法昆明小鼠随机分成5组(n=30):正常对照组、B(a)P组、番茄红素高[20mg/kg+B(a)P]、中[10mg/kg+B(a)P]、低[5mg/kg+B(a)P]3个不同剂量的实验组,实验组与B(a)P组给予B(a)P,建立前胃癌模型,观察不同浓度的番茄红素对小鼠前胃癌形成的作用;同时用单细胞凝胶电泳法检测外周血淋巴细胞DNA损伤情况,检测超氧化物岐化酶(SOD)、丙二醛(MDA)及谷胱甘肽过氧化物酶(GSH-Px)的含量。结果正常对照组未见肿瘤形成,其余4组均见肿瘤形成,并经病理证实。番茄红素高、中、低剂量组、B(a)P对照组前胃肿瘤发生率分别为50%、60%、80%、100%。与正常对照组相比,番茄红素高、中、低剂量组和B(a)P对照组MDA含量升高,SOD活性下降,DNA氧化损伤加重,差异有显著性(P<0.05)。与B(a)P对照组相比,番茄红素高剂量组MDA含量降低,高、中剂量组SOD活性升高,DNA氧化损伤减轻,差异有显著性(P<0.05)。番茄红素对GSH-Px影响不显著。结论番茄红素具有抑制肿瘤...     

小鼠前胃癌诱导过程中组织学与脂质过氧化

诱导小鼠前胃癌的化学物有多种 ,如苯并 (a)芘 [B(a)P]、甲基苄基亚硝胺、亚硝基肌氨酸乙酯等。其中用B(a)P诱导小鼠前胃癌的方法已经被多位学者用于抗癌物质的研究 ,证明抗癌物能抑制或延缓胃癌的发生〔1～ 4〕。为研究B(a)P诱导小鼠前胃癌过程中胃组织形态学的发展变化 ,本实验用B(a)P诱导小鼠前胃癌 ,观察胃组织形态学在胃癌形成过程中的变化。同时检测不同阶段血浆中丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)活力 ,并探讨胃癌与脂质过氧化之间的关系。1　材料与方法1 1　实验动物和分组　昆明种雌性小白鼠 2 10只 ,体重 17～ 2 0g …     

气相色谱分析法测定奶油中c9,t11-共轭亚油酸的含量

共轭亚油酸(conjugated linoleic acid,CLA)(以下简称CLA)是一类共轭双键位置在9和11或10和12的亚油酸(linoleic acid, LA)同分异构体的混合物,每个双键可以成顺式或反式构型[1],因而CLA最基本的空间构象是形成8种同分异构体[2].国外的大量研究表明,CLA具有很多重要的生物活性作用[3～10],如CLA具有抑癌作用、降低胆固醇和抗动脉粥样硬化作用、抗氧化作用,能有效地防止免疫刺激的分解代谢作用等,而c9,t11-CLA被认为是生物活性作用最强的共轭亚油酸异构体.目前,国内在CLA抑癌作用方面的研究已取得了很大的进展,但是关于食物中CLA含量的测定这一领域尚属空白.我们采用气相色谱内标法对奶油中c9,t11-CLA的含量进行定量测定.     

天然和加工奶酪中抗癌脂肪酸的鉴别和定量

作者曾从烤牛肉糜中分离出含共轭双键的C-9,C-12-十八碳二烯酸(亚油酸)的同分异构衍生物,称之为共轭亚油酸(CLA)。人工合成的CLA可部分阻止小鼠由7,12-二甲并[a]蒽诱发的上皮癌,以及由苯并[a]芘诱发的前胃肿瘤发生。已在人血清、胆汁和十二指肠液中分离出CLA,人类体液中CLA来源还不清楚。本文报道了在各种天然和加工奶酪中也有CLA,并开发了一种毛细管GC/反相HPLC技术可以从样品中分离9种CLA,并对CLA的来源和形成机制加以讨论。样品中的CLA先用梯度流动相(乙腈十水)的半制备反相柱分离,再用半制备正相柱以梯度系统纯     

药物代谢酶维生素E琥珀酸酯抑制苯并(a)芘

目的　探讨药物代谢酶在维生素E琥珀酸酯 (VES)抑制苯并 (a)芘毒性中的作用。方法　建立B(a)P诱导的小鼠前胃癌模型 ,观察不同途径投予VES对前胃癌的抑制作用。再选择最佳途径观察两相药物代谢酶在此过程中的变化。采用免疫荧光光度法检测小鼠肝脏微粒体 (S - 9组分 )中Ⅰ相药物代谢酶乙氧基异吩恶唑 0 -脱乙基酶(Ethoxyresorufin 0 -deethylase,EROD)活性 ;应用试剂盒测定S - 9组分中Ⅱ相药物代谢酶谷胱甘肽 -S -转移酶(GST)活性。结果　经口投予和腹腔注射VES均可明显降低B(a)P诱导的小鼠前胃癌的发生。VES可显著降低肝脏Ⅰ相药物代谢酶乙氧基异吩恶唑 0 -脱乙基酶 (EROD)的活性 (39 1± 3 0 5 ) ,与阳性对照组 (5 7 9± 3 16 )比较 ,有显著性差异。结论　VES可降低B(a)P诱导的小鼠前胃癌 ,作用机制可能是通过影响肝脏药物代谢酶的活性来实现。     

营养

诱导胃癌细胞凋亡中天冬氨酸特异性半胱氨酸蛋白酶的表达；富含单不饱和脂肪酸的坚果对高脂大鼠血脂水平的影响；共轭亚油酸抗缺氧效果及其机制的探讨；共轭亚油酸对正常动物细胞和人体肿瘤细胞间通讯功能的影响；共轭亚油酸对人胃腺癌细胞侵袭能力的影响及其作用机制；L-蛋氨酸驱铅对小鼠体内微量元素的影响；     

共轭亚油酸营养再分配作用及其安全性

共轭亚油酸(CLA)是一组具有共轭不饱和双键的亚油酸的位置和结构异构体,具有降脂增肌、促进生长、抗癌、抗动脉粥样硬化及调节免疫等生理功能。本文总结了CLA营养再分配活性及其安全性评价的研究成果,从分子药理水平,分析了CLA的作用机制与作用方式。     

Chemopreventive effect of turmeric against stomach and skin tumors induced by chemical carcinogens in Swiss mice.

The anticarcinogenic effect of dietary turmeric on benzo[a]pyrene-(BP) induced forestomach neoplasia and 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis in female Swiss mice was evaluated. To further elucidate the mechanism of antineoplastic action of turmeric, its effect on the hepatic cytochrome b5, cytochrome P-450, glutathione, and glutathione S-transferase activities was studied in female Swiss mice. Turmeric (2% or 5%) in the diet significantly inhibited the BP-induced forestomach tumors, and this response was dose and time dependent. The 2% turmeric diet significantly suppressed DMBA-induced skin tumors in mice. The 5% turmeric diet for seven consecutive days resulted in a 38% decrease in the hepatic cytochrome b5 and cytochrome P-450 levels. Glutathione content was increased by 12%, and the glutathione S-transferase activity was enhanced by 32% in the liver. Our results document a protective effect of turmeric on BP-induced forestomach and DMBA-induced skin tumors in mice.     

Effects of allyl methyl trisulfide on glutathione S-transferase activity and BP-induced neoplasia in the mouse

Allyl methyl trisulfide (AMT), a constituent of garlic oil, was studied for its effects on glutathione S-transferase (GST) activity and on benzo[a]pyrene (BP)-induced neoplasia of the forestomach and lungs of female A/J mice. AMT induced increased GST activity in the forestomach, small bowel mucosa, liver, and lung. The forestomach and small bowel mucosa responded to a single low dose of AMT (3.0 mumol) given by oral intubation, whereas liver and lung were less reactive. A dose schedule of two administrations of 15 mumol AMT given 48 hours apart gave close-to-maximum induction in all four tissues and was chosen for investigation of its inhibitory effects. With this dose schedule, AMT produced an inhibition of BP-induced neoplasia of the forestomach as shown by a greater than 70% reduction in the number of tumors found at the completion of the experiment. Inhibition of pulmonary neoplasia did not occur. AMT is a member of a new class of naturally occurring chemicals that have the capacity to inhibit chemical carcinogenesis.     

Effects of allyl methyl trisulfide on glutathione S‐transferase activity and BP‐induced neoplasia in the mouse

Allyl methyl trisulfide (AMT), a constituent of garlic oil, was studied for its effects on glutathione S‐transferase (GST) activity and on benzo[a]pyrene (BP)‐induced neoplasia of the forestomach and lungs of female A/J mice. AMT induced increased GST activity in the forestomach, small bowel mucosa, liver, and lung. The forestomach and small bowel mucosa responded to a single low dose of AMT (3.0 μmol) given by oral intubation, whereas liver and lung were less reactive. A dose schedule of two administrations of 15 μmol AMT given 48 hours apart gave close‐to‐maximum induction in all four tissues and was chosen for investigation of its inhibitory effects. With this dose schedule, AMT produced an inhibition of BP‐induced neoptasia of the forestomach as shown by a greater than 70% reduction in the number of tumors found at the completion of the experiment. Inhibition of pulmonary neoplasia did not occur. AMT is a member of a new class of naturally occurring chemicals that have the capacity to inhibit chemical carcinogenesis.     

小鼠前胃癌诱导中Cx32表达的变化

目的 探讨Cx32在胃癌癌前病变和胃癌组织中表达的动态变化。方法 B(a)P诱导小鼠前胃癌。免疫组织化学方法检测Cx32在小鼠前胃癌的发生、发展过程中表达的变化。结果在胃癌发生、发展过程中。Cx32表达呈现一个由高水平到低水平表达直至无表达的梯度分布，即Cx32在小鼠正常前胃粘膜层中高水平表达。在不典型增生中表达明显减少或不表达，在胃癌组织中无表达。结论 Cx32基因表达的异常与胃癌的发生关系密切。Cx32表达降低或消失，导致胃粘膜上皮细胞间隙连接通讯障碍，胃粘膜细胞去分化并恶性增殖。最终发展为胃癌。     

Dietary purified cis-9,trans-11 conjugated linoleic acid isomer has anticarcinogenic properties in chemically induced mammary tumors in rats

To determine whether the purified 9c,11t conjugated linoleic acid (CLA) isomer, the main dietary isomer, is biologically active on mammary tumor growth, we carried out a dietary intervention study designed to compare its effects with those of a mixture of CLA isomers on the incidence and growth of autochthonous mammary tumors induced by methylnitrosourea in rats. After the initiation step, rats were fed a sunflower oil-based diet (5%) and separated into three experimental groups supplemented with either a 1% homemade synthesized 9c,11t isomer, a 1% CLA isomer mixture, or free fatty acids prepared from sunflower oil for the control group. We found that, in the two CLA groups compared with the control group, CLA levels were about 30 times higher in mammary fat pads and about 10 times higher in tumor tissues. Compared with the control group, there was a 44% and 45% decrease in tumor mass per rat in the CLA mixture and the 9c,11t groups, respectively, at 20 wk of diet (P < 0.05). There was a nonsignificant trend for a decrease multiplicity in CLA groups compared with the control group, with a 30% and 35% decrease in the CLA mixture and the 9c,11t groups, respectively. Incidence and latency were not significantly different between the dietary groups. Although the effect was specifically restricted in reduction in tumor mass, we concluded that the main CLA isomer found in human diet has anticarcinogenic properties in experimental mammary carcinogenesis.     

Dietary conjugated linoleic acid lowers plasma cholesterol during cholesterol supplementation,but accentuates the atherogenic lipid profile during the acute phase response in hamsters

Conjugated linoleic acid (CLA) reportedly exerts anticarcinogenic and antiatherosclerotic effects in animals. To test the hypothesis that the putative antiatherosclerotic effect of CLA might derive from an anti-inflammatory or antioxidant action on lipoprotein metabolism, an acute phase response (APR) was elicited in hamsters while varying dietary cholesterol and vitamin E intakes in two experiments. The effect of CLA intake (to 1%) was examined with 0% (Experiment 1, 7 wk) and 0 or 0.3% (Experiment 2, 12 wk) cholesterol, at which point APR was induced. In hamsters not fed dietary cholesterol (Experiment 1), CLA exaggerated the rise in plasma and LDL cholesterol observed during the APR. When CLA was fed concurrently with cholesterol (Experiment 2), plasma and liver cholesterol were reduced up to 40% independent of the APR. In addition, CLA decreased body weight gain and adipose reserves in Experiment 1, but not in Experiment 2. Because CLA failed to attenuate APR and was not influenced by vitamin E status, an antioxidant/anti-inflammatory role was not apparent. However, the reduced burden on liver and lipoprotein cholesterol induced by CLA during cholesterol feeding, suggests that CLA curtailed cholesterol absorption, whereas the rise during APR suggests that CLA exaggerated the impaired clearance of plasma cholesterol associated with acute inflammation.     

Bioproduction of conjugated linoleic acid by probiotic bacteria occurs in vitro and in vivo in mice

Probiotics have been shown to reduce the incidence of colon cancer in animal models. The mechanisms responsible for this activity are poorly defined. Conjugated linoleic acids (CLA) are a group of isomers of linoleic acid (LA) possessing anti-inflammatory and anticarcinogenic properties, which can be produced from LA by certain bacterial strains. In this study, the ability of probiotic bacteria to exert anticarcinogenic effects through the production of CLA was assessed. Incubation of probiotic bacteria (VSL3, Lactobacillus acidophilus, L. bulgaricus, L. casei, L. plantarum, Bifidobacterium breve, B. infantis, B. longum, and Streptococcus thermophilus) in the presence of LA yielded CLA production as measured by gas chromatography. Conditioned medium, containing probiotic-produced CLA, reduced viability and induced apoptosis of HT-29 and Caco-2 cells, as assessed by MTT assay and DNA laddering, respectively. Western blotting demonstrated an increased expression of PPARgamma in cells treated with conditioned medium compared with LA alone. Incubation of murine feces with LA after administering VSL3 yielded 100-fold more CLA than feces collected prior to VSL3 feeding. This study supports a role for supplemental probiotics as a strategy both for attenuating inflammation and for preventing colon cancer.     

The anticarcinogenic effect of trans-11 18:1 is dependent on its conversion to cis-9, trans-11 CLA by delta9-desaturase in rats

The present study was designed to determine whether the ability of vaccenic acid (trans-11 18:1; VA) to reduce the risk of chemically induced mammary carcinogenesis in rats is direct or is mediated via conversion to cis-9, trans-11 conjugated linoleic acid (CLA). We previously reported that dietary VA caused a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in the risk of mammary tumorigenesis. Specifically, our objective was to determine whether inhibiting Delta9-desaturase with cyclopropenoic fatty acids, supplied by sterculic oil (SO), would reverse the cancer-protective effect observed with a dietary supplement of VA-enriched butter. Female Sprague-Dawley rats were injected with a single dose of carcinogen (methylnitrosourea) and were fed 1 of 4 diets: 1) low VA (0.13% of diet), 2) low VA + SO (0.4% of diet), 3) high VA (1.60% of diet), and 4) high VA + SO. After 6 wk, the mammary glands were evaluated histologically for the appearance of premalignant lesions and were stained with bromodeoxyuridine to determine the extent of cell proliferation, and fatty acids were analyzed in plasma, liver, and mammary fat pad. The VA-enriched diet increased the tissue content of CLA, reduced the risk of developing premalignant lesions, and decreased the proliferative activity of premalignant cells in the mammary gland. Treatment with SO reversed the effects of VA. The anticarcinogenic effect of VA is predominantly, perhaps exclusively, mediated through its conversion to cis-9, trans-11 CLA via Delta9-desaturase, and when this conversion is blocked by SO, the biological response to VA is attenuated.