大豆活性肽降低大鼠血浆胆固醇机理的初步探讨

目的探讨膳食大豆活性肽对高胆固醇模型大鼠血浆胆固醇及其有关血脂指标的影响,并对其可能的作用机理加以研究。方法4周龄断乳雄性Wistar大鼠,经28d诱导高胆固醇模型以后,按血浆总胆固醇浓度将动物均衡分为2组,分别喂饲含酪蛋白和大豆活性肽的纯合成高脂饲料56d。结果经28d诱导高胆固醇模型后,高胆固醇模型大鼠的TC浓度是阴性对照组的1.51倍。又经56d喂饲含有处理因素的饲料后,酪蛋白组和大豆活性肽组大鼠体重分别增加了（198.5和119.3）g;血浆总胆固醇浓度水平分别为（6.41±0.57和3.01±0.37）mmol/L;TG水平分别为（3.73±0.70和2.13±0.61）mmol/L;粪胆汁酸含量分别为（0.75±0.13和0.96±0.17）mmol/d;与酪蛋白组相比,大豆活性肽组动物体重及TC,TG和apoB含量显著降低,而粪胆汁酸含量显著增加（P〈0.05）。大豆活性肽组可使大鼠肝脏HMG-CoA还原酶 mRNA,LDL-R mRNA的表达增强。结论膳食大豆活性肽摄入可降低高胆固醇模型大鼠TC、TG、apoB浓度、使粪胆汁酸排泄量增高,但对HDL-C,apoA水平无影响。另外,大豆活性肽可以增强大鼠肝脏HMG-CoA还原酶及LDL-R基因的表达,这可能是其降低血浆胆固醇的机理之一。大豆活性肽可影响血浆胆固醇水平,但其相应的作用机理还需进一步探讨。     

FH clinical phenotype in Greek patients with LDL-R defective vs. negative mutations

BACKGROUND: Familial hypercholesterolaemia (FH) is caused by mutations in the low-density lipoprotein receptor gene and the gene encoding apolipoprotein B-100, affecting one in 500 individuals. METHODS: One hundred and eighty-three Greek FH patients were screened for mutations on the LDLR and ApoB genes. RESULTS: We identified mutations in 67 probands and 11 relatives. Sixteen mutations located in eight different exons and the promoter of the LDLR were discovered. Among them 10 were missense mutations (C6W, S265R, A370T, Q363P, D365E, V408M, A410T, A517T, G528D, G571E), two were nonsense mutations (Q363X and C660X), three were splice defects (2140 + 5G-->A and 2140 + 9C-->T, 1706 - 10G-->A), and one was a nucleotide substitution (- 45delT) on the promoter. None of the subjects carried any apoB mutation. The detection rate of mutations in this study was 43%. From the above mutations, A410T, A519T and the splice site defects 2140 + 9C-->T were detected for the first time in the Greek population. Among them V408M, G528D, C6W and S265R account for 73% of heterozygous FH probands. V408M mutation is more common in Central West, while C6W is more common in Central East. Separating the patients into two groups (receptor defective and receptor negative) we found that the receptor negative group had higher levels of total cholesterol, low-density lipoprotein cholesterol and higher prevalence of tendon xanthomas compared with the receptor-defective group. DISCUSSION: The homogenous molecular basis of familial hypercholesterolaemia in Greece facilitates the application of a DNA diagnostic strategy based on the origin of the patient. The early mutation analysis would add valuable information on the severity of the disease.     

脂脉宁对动脉粥样硬化家兔氧化应激反应及LDL-R, VCAM-1基因表达的影响

目的:探讨脂脉宁抗动脉粥样硬化(AS)的作用机制。方法:用高脂饲料复制家兔AS模型,于4周后再灌服脂脉宁4周,检测血脂、氧化指标及主动脉低密度脂蛋白受体(LDL-R)mRNA及血管细胞黏附分子-1(VCAM-1)mRNA的表达。结果:模型组血脂4项及超氧化物歧化酶(SOD)、丙二醛(MDA)均明显较空白组升高,谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)降低,主动脉内膜、斑块明显增厚;脂脉宁0.375,0.188 g.kg-1血脂及MDA含量均明显较模型组降低,GSH,GSH-Px升高,动脉斑块减小,高剂量组效果更明显。模型组LDL-R mRNA表达明显降低,VCAM-1 mRNA表达升高;给药2组LDL-RmRNA表达则明显升高,VCAM-1 mRNA表达降低,高剂量组尤为明显。结论:脂脉宁抗AS作用与其调整脂质代谢、抗氧化及调控LDL-R mRNA及VCAM-1 mRNA表达有关。     

Protective role of puerarin on lead-induced alterations of the hepatic glutathione antioxidant system and hyperlipidemia in rats

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of the present study was to investigate the effects of puerarin on hepatic oxidative stress and hyperlipidemia in rats exposed to lead. Our data showed that puerarin significantly prevented lead-induced hepatotoxicity, indicated by both diagnostic indicators of liver damage (serum aminotransferase levels) and histopathological analysis. Moreover, lead-induced profound elevation of ROS production and oxidative stress, as evidenced by increasing of lipid peroxidation level, reducing of GPx, GST, GR and GCL activities and depleting of intracellular reduced GSH level in liver, were suppressed by treatment with puerarin. Furthermore, the increase of serum cholesterol, triglycerides and LDL induced by lead was effectively suppressed by puerarin. The HDL level in the lead treatment rats was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidemia by regulating the expression of cholesterol 7a-hydroxylase (CYP7A1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and low-density lipoprotein receptor (LDL-R) in liver of lead treated rats. Altogether, these results suggest that puerarin could protect the lead-induced liver injury and hyperlipidemia by reducing ROS production, renewing the activities of antioxidant enzymes and influencing expression of hepatic lipid biosynthesis and metabolism genes.     

Autosomal Recessive Hypercholesterolemia: Long-Term Cardiovascular Outcomes

Background

Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH.

山楂总黄酮对复合因素致大鼠脂肪肝模型脂质代谢与低密度脂蛋白受体 表达的影响

目的 研究山楂总黄酮对复合因素致大鼠脂肪肝模型脂质代谢与低密度脂蛋白受体（LDL-R）表达的影响。方法 采用复合因素致大鼠脂肪肝动物模型。造模成功后将动物随机分成6组,分别ig给予山楂总黄酮 0.3、0.6、1.2 g/kg,东宝甘泰0.6 g/kg,模型组和对照组每天ig给予等体积生理盐水。造模后、给药期间、末次给药后分别检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（AKP）活性,以及三酰甘油（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）水平;末次给药后检测血液流变学指标和肝组织匀浆TG和TC水平,同时取肝左叶分别用于病理检查观察显微结构变化,RT-PCR和免疫组化检测LDL-R mRNA和蛋白表达。结果 山楂总黄酮作用于复合因素致脂肪肝大鼠模型,其血清中脂质、肝TC和肝TG与模型组比较有显著性降低;血清ALT、AST和AKP活性与模型组比较有显著性降低;山楂总黄酮能明显降低全血黏度（高切和低切）、红细胞聚集指数、红细胞压积以及明显增加红细胞变形指数;病理组织学检查显示,各给药组脂肪变性和炎症反应程度较模型组均有一定的减轻。RT-PCR和免疫组化结果显示,模型组大鼠肝组织LDL-R mRNA和蛋白表达与对照组比较显著降低（P＜0.05）。山楂总黄酮和东宝甘泰对复合因素致脂肪肝模型大鼠肝组织LDL-R mRNA和蛋白表达降低有明显抑制作用。结论 山楂总黄酮可能通过调节脂肪代谢、改善肝脏功能和增加LDL-R mRNA和蛋白的表达,起到治疗大鼠脂肪肝的作用。     

Cholesterol-lowering effect of Aralia elata (Miq.) Seem via the activation of SREBP-2 and the LDL receptor

Background

Hyperlipidemia causes arteriosclerosis, a risk factor for coronary heart disease. Prevention of hyperlipidemia by improving dietary habits has recently attracted attention. In this regard, we investigated whether Aralia elata (Miq.) Seem (AE) extract inhibits hepatic cholesterol accumulation and modulate the cellular signaling pathway.