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1.
Abstract

Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets are known to alter brain morphology and reproductive endocrine parameters. This study characterized dietary phytoestrogens' effect on retinal thickness in male and female Long-Evans rats. Experiment 1a and 1b: upon arrival (50 day-old) animals received either a phytoestrogen-rich diet (containing 600 μg phytoestrogen/g diet; referred to as Phyto-600) or a diet low in phytoestrogens (Phyto-free). Males remained on these diets until 140 days of age (females until 160 days of age). In both sexes a significant (but opposite) diet difference in retinal thickness was identified. Male Phyto-600 and female Phyto-free animals had significantly greater retinal thickness compared to Phyto-free males and Phyto-600 females, respectively. Experiment 2: male or female rats were raised from conception on either the Phyto-600 or Phyto-free diet until sacrifice at 75 days of age. Consistent with experiment 1, males exposed to the Phyto-600 diet lifelong had significantly greater retinal thickness than lifelong fed Phyto-free males (no significant differences were identified in females). These data suggest that phytoestrogens influence rat retinal characteristics in a sexually dimorphic manner (more robust effect in males vs. females) and that this influence can occur even in adulthood.  相似文献   

2.
Tocopherols are present in significant amounts in vegetable oils used in human foods. The most prevalent tocopherols in foods are the α, β, γ, and δ variants with (RRR) stereochemistry. Tocopherols are lipophilic phenolic antioxidants, produced by plants. In the United States, γ -tocopherol is the most prominent dietary tocopherol due to its high amount in the dominant commercially produced vegetable oils such as soybean, corn, and cottonseed. In this report, experiments were designed to study the inhibitory effect of mixed tocopherols against N-methyl-N-nitrosourea-induced mammary tumor growth in female Sprague-Dawley rats. Beginning at 21 days of age, rats were treated with a single intraperitoneal injection of 50 mg/kg body weight of N-methyl-N-nitrosourea. One wk later, the rats were fed experimental diets containing 0 or 0.1% mixed tocopherols containing over 50% γ -tocopherol. At 9 wk after N-methyl-N-nitrosourea treatment, all rats were evaluated for inhibition of mammary tumor growth and proliferating cell nuclear antigen. Dietary administration of mixed tocopherols significantly suppressed mammary tumor growth (P < 0.05) and proliferating cell nuclear antigen (P < 0.01) and also moderately suppressed tumor multiplicity. The treatment increased the serum levels of γ - and δ -tocopherols without affecting the body weight. The results of this study suggest that mixed tocopherols may be safe and effective agents for the prevention of breast cancer.  相似文献   

3.
There are conflicting reports on the effect of soy and its components on mammary carcinogenesis in adult female rats, mainly because of different rodent models that are used in chemoprevention studies. The present study was undertaken to compare the tumor-preventative effects of soy protein isolate (SPI) and two of its isoflavones in a "standard" model that had been used for the identification of many chemopreventive agents. Six groups of female Sprague-Dawley rats were provided with modified cornstarch AIN-76A diets supplemented as follows: no additional agents (control), purified genistein (200 mg/kg diet), purified daidzein (200 mg/kg diet), genistein + daidzein (100 mg/kg diet each), SPI containing normal levels of isoflavones (SPI-n), or SPI depleted of isoflavones (SPI-d). Mammary carcinomas were induced by 7,12-dimethylbenz[a]anthracene (DMBA) introduced 1 wk after the animals began consuming the experimental diets. At the end of the study (120 days after DMBA treatment), no significant differences were found among the six groups with respect to tumor incidence or survival, nor was there a significant reduction in tumor multiplicity in the genistein or genistein + daidzein group. However, there was a 32% reduction in tumor multiplicity in the daidzein and SPI-n groups relative to the control group (P ? 0.05). The most effective diet was SPI-d, which produced a 50% reduction in tumor multiplicity relative to the control (P ? 0.01). The difference between the SPI-d group and the daidzein or SPI-n group was not significant. Median tumor latency was increased from 53 days in the control group to 68 days in the daidzein group and to 72 days in the SPI-d group, but these differences were not statistically significant. These results show that daidzein and SPI (with normal or low levels of isoflavones) are effective inhibitors of DMBA-induced mammary tumors in adult rats.  相似文献   

4.
In this study, the effects of dietary fatty acids on the fatty acid compositions and lipid metabolic-related genes expression in N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis were evaluated. The 50-day-old female Sprague-Dawley rats were intervened by different dietary fats (15% wt/wt), including saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-6 polyunsaturated fatty acid (PUFA), n-3 PUFA, 1:1 n-6/n-3, 5:1 n-6/n-3, 10:1 n-6/n-3, and 1:2:1 S/M/P (1:1 n-6/n-3), alone or in combination with MNU. There was no mammary tumor occurrence in the control and MNU-treated n-3 PUFA groups after 18 wk. n-3 PUFA diet retarded the weight growth of rats. 1:1 n-6/n-3 diet significantly reduced the MNU-induced tumor incidence and tumor multiplicity compared with SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and 1:2:1 S/M/P diets (42.86% vs. 83.33%–92.31%, 0.79 vs. 2.62–2.85, P < 0.01). Additionally, 1:1 n-6/n-3 diet substantially increased cis-5,8,11,14,17-eicosapentaenoic acid and cis-4,7,10,13,16,19-docosahexaenoic acid levels, whereas it decreased C20:4 level and the mRNA expressions of fatty acid synthase, Cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) in mammary tissues (P < 0.05). These results suggest that 1:1 n-6/n-3 in the diet is effective in the prevention of mammary tumor development by increasing the n-3 PUFA content and reducing the expression of lipid metabolic-related genes.  相似文献   

5.
维生素E对DMBA诱导的大鼠乳腺肿瘤的抑制作用   总被引:1,自引:0,他引:1  
目的 研究维生素E对乳腺癌的抑制作用。方法 把出生50天的雌性SD大鼠(体重约176g)随机分为4组:阴性对照组、阳性对照组、低剂量组和高剂量组。除阴性对照组外其余每只大鼠经灌胃给致癌剂(DMAB),每只15mg溶于1.5的植物油中,给予致癌剂的同时给低剂一组和高剂量组大鼠含维生素E的饲料,对照组大鼠喂基础饲料,持续喂养24周。结果 表明阳性对照组、低剂量组、高剂量组大鼠乳腺肿瘤的发生率分别为75.0%、52.4%、34.8%有显性差异,同时病理组织学观察也有一定差别。结论 维生素E可能对乳腺癌具有化学预防作用。  相似文献   

6.
Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.  相似文献   

7.
Abstract

A deficiency of sex hormones affects brain function in mammals, including the decrease of protein synthesis. Recently, we have shown that the protein synthesis in the brain depended on the quality of dietary protein in ovariectomized female rats. The methionine is the first limiting amino acid for the recommended dietary allowance of amino acids in soy protein. The purpose of this study was to determine whether the addition of dietary methionine affected the rate of brain protein synthesis in ovariectomized female rats fed on the soy protein diet. Experiments were conducted on two groups of ovariectomized female rats (24 week) given the diets containing 5% soy protein or 5% soy protein+0.2% methionine for 10 d. The fractional rates of protein synthesis in cerebral cortex and cerebellum significantly increased with an addition of dietary methionine. In the brain, the RNA activity [g protein synthesized/((g RNA)· d)] was significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg of RNA/g of protein) was not related to the fractional rate of protein synthesis in any organ. The results suggest that the addition of limiting amino acid for the low soy protein elevates the rate of protein synthesis in the brain of ovariectomized female rats, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.  相似文献   

8.
Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectal cancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects. Since both melatonin and glycine have anti-cancer activities without relevant side effects, this study was designed to investigate their combined effects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced in male Wistar rats. Melatonin and glycine alone or their combination were supplemented for 14 days (n = 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), and immunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared between groups. Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p = 0.002) and 43% (p = 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls. Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters. The leukocyte count was significantly increased with melatonin at the end of the experiment (p = 0.012) which was due to a high lymphocytes count. Tumor microvascular density was significantly reduced in all treatment groups. The results of this study suggest an inhibitory function for melatonin and glycine alone in the case of CRC liver metastasis growth by acting as natural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation and immunomodulation.  相似文献   

9.
Estrogen receptor (ER) and/or progesterone receptor (PR) expression has been associated with more favorable breast cancer prognosis. Results on the differential association of diet with ER and/or PR positive and negative tumors have been inconclusive. In a large case-control study conducted in Athens, Greece, we investigated whether diet is associated with the expression of ER-alpha or PR in mammary tumors of 421 women with histologically confirmed breast cancer. Diet was assessed through an extensive food frequency questionnaire and results were analyzed using multiple logistic regression. After controlling for non-nutritional variables and mutually adjusting for energy-generating nutrients and ethanol, carbohydrate intake was inversely associated with ER-alpha (P = 0.04) and PR (P = 0.10) expression. The odds ratios (OR) per one standard deviation increment were 0.69 with 95% confidence interval (95% CI) 0.48-0.98 for ER-alpha and 0.72 (95% CI 0.49–1.07) for PR expression. No consistent or statistically significant associations were noted for any of the other energy-generating nutrients or food groups examined. Although in these data no strong relations of qualitative aspects of diet with hormone receptor expression in breast cancer tumors were evident, the inverse association of carbohydrate intake with ER-alpha, and perhaps PR, expression merits further study in future investigations.  相似文献   

10.
健康促进理论在体力活动促进中的应用   总被引:2,自引:0,他引:2  
李洋  傅华 《中国健康教育》2004,20(2):138-141
健康促进理论起源于行为学的认知心理学理论 ,在其自身的发展完善过程中借鉴和吸收了市场学、传播学、组织理论、生态学理论等多种社会学理论体系的成分。健康促进理论为健康促进项目提供了理论性的框架 ,在健康促进项目的设计、实施和评价中发挥着指导性作用。健康促进理论主要可以被概括为个体水平 ,人际水平和群组、社区水平 3个层面 ,另外 ,在健康促进实践中运用这 3个层面的健康促进理论时 ,可以借鉴和遵循PRECEDE -PROCEDE模式、社会市场学理论或生态学模式 ,以在操作中对各个层面上的健康促进理论进行组织和协调[1 ] 。规律的…  相似文献   

11.
Gliomas are tumors of glial origin formed in the central nervous system and exhibit profound morphological and genetic heterogeneity. The etiology of this heterogeneity involves an interaction between genetic alterations and environmental risk factors. Scientific evidence suggests that certain natural dietary components, such as phytoestrogens, flavonoids, polyunsaturated fatty acids, and vitamins, may exert a protective effect against gliomas by changing the nature of the interaction between genetics and environment. Similarly, certain antiinflammatory drugs and dietary modifications, such as methionine restriction and the adoption of low-calorie or ketogenic diets, may take advantage of glioma and normal glial cells’ differential requirements for glucose, methionine, and ketone bodies and may, therefore, be effective as part of preventive or treatment strategies for gliomas. Treatment trials of glioma patients and chemoprevention trials of individuals with a known genetic predisposition to glioma using the most promising of these agents, such as the antiinflammatory drugs curcumin and gamma-linolenic acid, are needed to validate or refute these agents’ putative role in gliomas.  相似文献   

12.
Genistein, a major soy isoflavone having weak estrogenic activities, has been suggested to reduce the risk of breast cancer incidence. However, many studies have yielded inconsistent results. We investigated the effects of dietary genistein on the development of breast cancer using ethyl methanesulphonate (EMS) chemically induced rat model of hormone-dependent mammary carcinoma. Female Wistar King A rats were orally given EMS for 12 wk and fed isoflavone-free NIH-07PLD diets with or without genistein, beginning immediately after weaning period. All EMS-treated rats fed either diet developed estrogen and/or progesterone receptor-positive mammary carcinoma by 24 wk. The addition of either low or high genistein, which produced the plasma concentrations comparable with those observed in humans consuming high soy diets, did not show any preventive activity. Soy-containing pellet food, exhibiting substantial plasma concentrations of isoflavones such as genistein, daidzein, equol, and glycitein, significantly increased the latency periods, compared to either NIH-07PLD diet with low (P = 0.027) or high (P = 0.034) genistein. Body weights, total EMS uptakes, and urinary estradiol concentrations were not significantly different among groups. These data indicate that genistein does not exert clear preventive effects and that isoflavone components other than genistein might be preventive against hormone-dependent mammary carcinogenesis.  相似文献   

13.
茶多酚抑制促癌物TPA促癌作用抗氧化机制研究   总被引:9,自引:1,他引:8  
祁禄  韩驰 《卫生研究》1998,27(1):50-52
用促癌物TPA涂抹小鼠皮肤,并涂抹绿茶多酚(GTP)。结果表明:GTP可明显抑制涂抹TPA诱导的鸟氨酸脱羧酶(ODC)活性增高及某些抗氧化酶(CAT、GR、GST)活性降低。另外,在体外试验中加入0.2、0.4、0.8mg/LGTP可明显抑制TPA诱发大鼠多型核白细胞(PMNs)生成的过氧化氢,并有一定的剂量—反应趋势。上述结果表明GTP抑制TPA促癌作用的机制可能与其抗氧化作用有关。  相似文献   

14.
目的 研究p53基因mRNA及蛋白在大鼠肝促癌过程中的表达及作用。方法 雄性Wistar大鼠随机分为6组:高、中、低剂量组,启动对照组、促癌对照组、正常对照组。高、中、低剂量组、启动对照组建立大鼠肝癌二阶段启动-促进模型。高、中、低剂量组分别给予含500、100、50mg/kg苯巴比妥的饲料;启动对照组只给予基础饲料;促癌对照组不启动,只给予含500mg/kg苯巴比妥的饲料;正常对照组不给予任何处理因素。各组给予苯巴比妥后的第1、5、10、15、20、30周,以免疫组化亲和链霉素-生物素-过氧化酶法检测促肝癌过程中p53基因蛋白表达,原位杂交检测p53 mRNA表达。结果 经启动处理的各组大鼠肝癌前病变可见突变型p53(mtp53)蛋白表达。当给予高剂量和中剂量促癌物处理后,p53蛋白表达增高。低剂量组和启动对照组p53蛋白表达高于正常,但随着促癌物给予时间的延长未见明显改变。正常对照组和促癌对照组野生型p53 mRNA(wtp53)表达水平很低。经启动处理的高、中、低剂量组和启动对照组wtp53 mRNA高于正常组。高、中剂量组随着促癌物给予时间的延长,wtp53 mRNA表达降低,低剂量组和启动对照组随着时相点延长wtp53 mRNA略呈增高趋势。结论 p53参与大鼠肝癌促癌过程,可能由促癌物引起p53的下调和突变,导致不利于修复和凋亡的环境,有利于癌前肝细胞克隆增生,从而促进肝癌形成。  相似文献   

15.
Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.  相似文献   

16.
不同膳食纤维对大鼠体内脂质过氧化作用的影响   总被引:4,自引:2,他引:4  
宋扬  吴晖云 《卫生研究》1997,26(5):318-320
考察了3种不同膳食纤维——纤维素、麦麸、果胶对高脂膳食大鼠体内脂质过氧化程度的影响。40只Wistar大鼠被随机分为4组,其中3组分别给与10%的3种膳食纤维,喂养3个月后发现,膳食纤维组大鼠粪便中脂肪排出量增多,血清中及红细胞膜MDA水平均显著地低于对照组(P<0.05),红细胞膜的流动性显著地高于对照组(P<0.05),说明3种膳食纤维均可降低大鼠体内的脂质过氧化水平,减少自由基对生物膜的损伤。  相似文献   

17.
Methylglyoxal is a precursor to advanced glycation endproducts that may contribute to diabetes and its cardiovascular-related complications. Methylglyoxal is successively catabolized to d-lactate by glyoxalase-1 and glyoxalase-2. The objective of this study was to determine whether dietary fructose and green tea extract (GTE) differentially regulate methylglyoxal accumulation in liver and adipose, mediated by tissue-specific differences in the glyoxalase system. We fed six week old male Sprague-Dawley rats a low-fructose diet (10% w/w) or a high-fructose diet (60% w/w) containing no GTE or GTE at 0.5% or 1.0% for nine weeks. Fructose-fed rats had higher (P < 0.05) adipose methylglyoxal, but GTE had no effect. Plasma and hepatic methylglyoxal were unaffected by fructose and GTE. Fructose and GTE also had no effect on the expression or activity of glyoxalase-1 and glyoxalase-2 at liver or adipose. Regardless of diet, adipose glyoxalase-2 activity was 10.8-times lower (P < 0.05) than adipose glyoxalase-1 activity and 5.9-times lower than liver glyoxalase-2 activity. Adipose glyoxalase-2 activity was also inversely related to adipose methylglyoxal (r = −0.61; P < 0.05). These findings suggest that fructose-mediated adipose methylglyoxal accumulation is independent of GTE supplementation and that its preferential accumulation in adipose compared to liver is due to low constitutive expression of glyoxalase-2.  相似文献   

18.
The association between soy food and soy isoflavone intake and cardiovascular disease (CVD) risk is uncertain, especially in women. We aimed to investigate this association in Korean women. We analyzed data from the Korean Genome and Epidemiology Study, including 4713 Korean women aged 40–69 years with no CVD or cancer at baseline. Dietary information was obtained using a validated semi-quantitative food frequency questionnaire, and the incidence of CVD was assessed using biennial self-reported questionnaires on medical history. The mean follow-up time was 7.4 years, during which 82 premenopausal and 200 postmenopausal women reported CVD incidence. The highest tofu, total soy foods, and dietary soy isoflavone intake groups were significantly associated with a decreased CVD risk in premenopausal women (tofu: hazard ratio (HR) 0.39; 95% confidence interval (CI), 0.19–0.80; total soy food: HR 0.36; 95% CI, 0.18–0.70; dietary soy isoflavones: HR 0.44; 95% CI, 0.22–0.89), whereas no association was observed in postmenopausal women. Other soy foods showed no association with CVD incidence. Dietary soy isoflavones and total soy foods are associated with a decreased CVD risk in premenopausal women. Among soy foods, only tofu showed significant health benefits.  相似文献   

19.
将96只刚断乳WAK纯品系雄性大鼠随机分成4组,每组又分成4个亚组(6只/亚组),分别喂饲含5%、10%、15%、20%蛋白质及2ppm、6ppm、15ppm、30ppm锌各指定饲料8周。在最后1周,测定食物、粪便、尿液中氮含量。结果尿氮随膳食蛋白质水平增加明显增加(P<0.05),粪氮损失随膳食锌摄入水平增加而明显降低,含锌2ppm、6ppm组表现氮潴留率明显低于15ppm、30ppm含锌组110%蛋白质水平和15ppm膳食锌时氮潴留率为最大。同时,蛋白质水平组≥10%各组,尿氮、粪氮与血浆蛋白、血浆锌呈负相关(P<0.05);而5%的蛋白质水平组,血浆蛋白、血浆锌只与尿氮有相关关系(P<0.01),而与粪氮无关(P>0.05).说明本试验条件下:低蛋白膳食,锌对氮潴留影响意义不大,不是唯一的限定因素,只是一非控制因素;在适宜和较高水平的蛋白质摄入情况下,锌对氮潴留影响有重要意义,是一控制因素。  相似文献   

20.
大豆异黄酮对去睾丸大鼠血糖及血脂的调节作用研究   总被引:1,自引:0,他引:1  
目的 研究环境内分泌干扰物--植物雌激素大豆异黄酮(soy isoflavones,SIF)对去睾丸雄性大鼠血糖及血脂的调节作用.方法 将54只健康7周龄清洁级雄性Wistar大鼠按体重随机分为6组,分别为假手术组(SHAM)、去睾丸对照组(ORCH)、低剂量大豆异黄酮组(L-SI)、中剂量大豆异黄酮组(M-SI)、高剂量大豆异黄酮组(H-SI)和雌激素对照组(EC),每组9只.用1.5%戊巴比妥钠按40 mg/kg腹腔注射麻醉,除假手术组进行单纯开腹手术外,其余5组均摘除睾丸.高脂饲料喂养4周,其中,低、中、高剂量大豆异黄酮组每kg高脂饲料分别加入大豆异黄酮1、3、9 g,雌激素对照组每kg高脂饲料中加入已烯雌酚0.45 mg.在第2、4周分别检测大鼠胰岛素、空腹血糖(FBG)及血脂[甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)]水平.结果 去除睾丸后大鼠的体重显著下降,差异均有统计学意义(P<0.05).与雌激素对照组比较,假手术组、去睾丸对照组和高、中、低剂量大豆异黄酮组大鼠体重均较高,差异有统计学意义(P<0.05).大鼠体重多随着大豆异黄酮染毒剂量的升高而降低.与去睾丸对照组相比,第4周高、中、低剂量大豆异黄酮组大鼠血糖均显著下降,中、高剂量大豆异黄酮组大鼠胰岛素水平显著升高,差异均有统计学意义(P<0.05).大豆异黄酮和雌激素可显著降低大鼠TC水平(P<0.05),而对LDL无明显影响(P<0.05),不能改善大鼠HDL水平(P<0.05),对TG有一定的降低作用,但差异无统计学意义(P>0.05).结论 大豆异黄酮可通过提高去睾丸大鼠体内胰岛素水平而发挥降血糖作用,可显著降低TC水平,对TG具有一定的调节作用,但对HDL和LDL无明显影响.  相似文献   

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