【作者】 张治国；

【导师】 李铎；

【作者基本信息】 浙江大学 ， 食品科学， 2008， 博士

【摘要】 T2DM(type 2 diabetes mellitus,T2DM)在世界范围内日益流行,胰岛素抵抗是T2DM发展的早期阶段和决定因素。高糖高脂饮食是胰岛素抵发展的饮食基础。醋具有降低餐后血糖应答和降血脂的作用,乙酸是其主要的功效成分。本论文以研究乙酸(醋中的挥发性酸)的降血脂作用为出发点,研究了乙酸对模拟脂饲料(模拟我国城镇居民膳食脂肪组成)饲喂大鼠的胰岛素敏感性的改善作用,以及乙酸和醋粉(醋中的非挥发性成分总和)对高果糖饮食诱导的大鼠胰岛素抵抗的预防作用,并通过人体实验初步评价了醋粉的安全性。主要结果如下:1).AIN-93G标准饲料、高脂饲料(15%大豆油和1%胆固醇)及含低(0.1%)、中(0.2%)、高(0.4%)浓度乙酸的高脂饲料饲喂ICR小鼠3周。高脂饲料导致小鼠禁食血浆和肝脏甘油三酯(TG)、总胆固醇(TC)水平显著升高(p＜0.05),内脏脂肪比率显著增加(p＜0.05)。与高脂组相比,中浓度和高浓度组血浆TG、TC和肝脏TC水平显著降低(p＜0.05)。低浓度组血浆TC也显著低于高脂组(p＜0.05)。中浓度组内脏脂肪比率显著降低(p＜0.05)。各乙酸浓度组中,乙酸中浓度组的血浆和肝脏TG、TC以及内脏脂肪比率均最低。2).用AIN-93G饲料(C组)、模拟脂饲料(M组,饲料脂肪总量为8.5%,其中大豆油为60.4%,猪油为39.6%)、含0.2%乙酸的对照饲料(CA组)和含0.2%乙酸的模拟脂饲料(MA组)饲喂SD大鼠10周。与C组相比,M组血浆高密度脂蛋白胆固醇(HDL-C)显著降低(p＜0.05),低密度脂蛋白胆固醇(LDL-C)、非酯化脂肪酸(NEFA)和胰岛素水平显著升高(p＜0.05)。肝素处理前血浆脂蛋白脂酶(LPL)活性显著降低(p＜0.05)。肝脏TG、TC含量和肝总脂酶活性显著升高(p＜0.05)。与M组相比,MA组血浆HDL-C和APOAI水平显著升高(p＜0.05)、LDL-C和APO B100以及胰岛素水平显著降低(p＜0.05)。肝总脂酶活性显著降低(p＜0.05),肝素处理前血浆LPL活性显著升高(p＜0.05)。此外,与C组相比,CA组血浆APOAI水平显著升高(p＜0.05)。3).用AIN-93G饲料(C组),高果糖饲料(F组)、高果糖加0.2%乙酸(FA组)、高果糖加0.68%醋粉(FP组)、高果糖加0.2%乙酸加0.68%醋粉饲料(FAP组)饲喂SD大鼠8周。与C组相比,F组禁食血浆TG、TC、HDL-C、LDL-C、葡萄糖、胰岛素和血清尿酸水平显著升高(p＜0.05),肝TG、TC、NEFA含量显著升高,胰岛素抵抗指数(HOMA-IRI)以及口服糖耐量实验(OGTT)的血糖曲线下面积(AUC)显著升高(p＜0.05)。与F组相比,FA组、FAP组血浆TG、LDL-C、胰岛素、血清尿酸水平,肝TG、TC、NEFA含量均显著降低(p＜0.05)。此外,AUC和血浆HDL-C水平HOMA-IRI在FA组也显著降低(p＜0.05)。FP组肝TG、NEFA显著降低(p＜0.05)。4).与C组相比,F组肝糖原含量、肝丙酮酸激酶(PK)、过氧化氢酶(CAT)、超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性显著降低(p＜0.05);肝葡萄糖-6-磷酸酶(G-6-Pase)和葡萄糖-6-磷酸脱氢酶(G-6-PDHase)活性和肝丙二醛(MDA)含量显著升高(p＜0.05)。肝总脂肪酸(TFA)中,饱和脂肪酸(SFA)的比率显著升高(p＜0.05),多不饱和脂肪酸(PUFA)的比例显著降低;C18:0、C18:1、C20:4 n-6比例显著升高(p＜0.05),C18:2n-6、C18:3n-3、C20:5n-3、C20:1、C20:2比例显著降低(p＜0.05)。与F组相比,肝糖原含量在FA组、FAP组显著升高(p＜0.05)。肝PK活性在FA、FP、FAP都显著升高(p＜0.05)。肝G-6-Pase在FA组和FAP组都显著降低(p＜0.05),肝G-6-PDHase仅在FA组表现出显著降低(p＜0.05)。肝CAT酶在FA组显著升高(p＜0.05);肝GSH-Px活性在FAP组显著升高(p＜0.05)。肝TFA中,SFA在FAP组显著降低(p＜0.05),PUFA在FA组显著升高(p＜0.05)。C18:1在FA、FAP组显著降低(p＜0.05),C18:2n-6脂肪酸在FAP组显著升高(p＜0.05)。5).健康成年人每日摄入2.5g米醋粉16周后,血清总蛋白、白蛋白和尿酸水平显著升高(p＜0.05),但这些参数的变化都在正常生理范围内。膳食乙酸补充具有降脂作用,0.2%乙酸浓度降脂效果最显著。乙酸补充有助于改善胰岛素敏感性,其作用与乙酸降低脂肪组织LPL活性和肝总脂酶活性,调节肝TG代谢有关。乙酸和醋中的非挥发性成分都对高果糖饮食引起的胰岛素抵抗有不同程度的预防作用。二者的作用途径都与抑制肝TG积累和NEFA水平、降低肝脏中C18:1和提高C18:2n-6脂肪酸比例有关。此外,乙酸的作用还与减轻氧化应激程度、抑制肝糖异生有关。每日2.5 g醋粉的摄入对人健康人是安全的,并且促进肝白蛋白合成。但由于存在升高血清尿酸的作用,高尿酸血症患者应谨慎食用。更多还原

【Abstract】 The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly in the worldwide. Insulin resistance is the determinant factor for the development of type 2 diabetes. It most often precedes the onset of T2DM by many years. High sugar/high fat diets are the dietary causes of T2DM. Vinegar has been demonstrated to have positive effects on lowering postprandial blood glucose response and anti-hyperlipidemia. Acetic acid was regarded as the main effective component in vinegar.In the present study, we studied the effects of acetic acid (the volatile acid in vinegar) on anti-hyperlipidemia in ICR mice fed on a high lipid diet and on insulin sensitivity of rats fed on a modeling diet, which has similar lipid load with the diet of Chinese town residents. We further compared the preventive effects of acetic acid and vinegar powder (the total nonvolatile components in vinegar) on insulin resistance in rats fed on a high fructose diet. We also evaluated the safety of vinegar powder with a human study. The main results summarized as follows:1) ICR mice were fed on a AIN-93G diet, a high lipid diet (15 % soybean oil and 1 % cholesterol) and diets with low (0.1 %), medium (0.2 %) or high (0.4 %) acetic acid concentrations for 3 weeks. High lipid diet increased plasma and liver triacylglycerol (TG), total cholesterol (TC) levels and the ratio of visceral adipose weight to body weight significantly (p<0.05). Compared with high lipid diet group, plasma TG, TC levels and liver TC contents decreased significantly in the medium and high concentration groups (p<0.05). Plasma TC also decreased signifieantly in low concentration (p<0.05). The ratio of visceral adipose weight to body weight decreased significantly in the medium concentration group (p<0.05). Among three acetic acid concentration groups, the medium concentration group showed lowest plasma and liver TG, TC levels and the ratio of visceral adipose weight to body weight.2) SD Rats were fed on a AIN-93G diet (C group), a modeling diet (M group, lipid content was 8.5% and was composed of 60.4 % soybean oil and 39.6 % lard), a AIN-93G diet with 0.2 % acetic acid (CA group) and a modeling diet with 0.2 % acetic acid (MA group) for ten weeks. Compared with the C group, the M group showed significant decrease in plasma high density lipoprotein cholesterol (HDL-C) but significant increases in plasma low density lipoprotein cholesterol (LDL-C), nonesterified fatty acid (NEFA) and insulin levels (p<0.05). Preheparin plasma lipoprotein lipase (LPL) activity in the M group decreased significantly (p<0.05). Liver TG, TC contents and hepatic total lipase activity in the M diet group increased significantly (p<0.05). Compared with the M group, the MA group showed significant increases in plasma HDL-C and apolipoprotein AI (APO AI) levels but significant decreases in plasma LDL-C, apolipoprotein B100 and insulin levels (p<0.05). Hepatic total lipase activity decreased signifieantly in the MA group (p<0.05). Prehepatin plasma LPL activity increased signifieantly in this group (p<0.05). Compared with the C group, plasma APO AI level increased significantly (p<0.05).3) SD rats were fed on a AIN-93G diet (C Group), a high fructose diet (60 % fructose) (F group), high fructose diets with 0.2 % acetic acid (FA group), 0.68 % vinegar powder (FP group) or 02 % acetic acid + 0.68 % vinegar powder (FAP group) for 8 weeks. Compared with the C group, the F group showed significant increases in fasting plasma TG, TC, HDL-C, LDL-C, glucose, insulin levels and serum uric acid level (p<0.05). Liver TG, TC, NEFA contents also increased signifieantly in the F group (p<0.05). Homeostatic model assessment of insulin resistance index (HOMA-IRI) and area under blood glucose curve (AUC) in oral glucose tolerance test (OGTT) increased signifieantly in the F group (p<0.05). Compared with the F group, the FA group and FAP group showed significant decrease in plasma TG, LDL-C and insulin levels, serum uric acid level and liver TG, TC and NEFA contents (p<0.05). AUC, HOMA-IRI and plasma HDL-C level in the FA group decreased signifieantly, also (p<0.05). The FP group showed significant decreases in liver TG and NEFA contents (p<0.05).4) Compared with the C group, the F group showed significant decreases in liver glycogen contents, hepatic pyruvate kinase (PK), Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities but significant increases in hepatic glucose-6-phorsphatase (G-6-Pase), glucose-6-phorsphate dehydrogenase (G-6-PDHase) activities and malondialdehyde (MDA) contents (p<0.05). The percentage of saturated fatty acid (SFA) in total fatty acid (TFA) of liver significantly increased in the F group (p<0.05), while the percentage of polyunsaturated fatty acid (PUFA) decreased significantly (p<0.05). Additionally, the F group showed significant increases in the percentages of C18:0, C18:l, C20:4 n-6 fatty acids but significant decreases in the percentage of C18:2 n-6, C18:3 n-3, C20:5 n-3, C20:l, C20:2 fatty acids in TFA of liver (p<0.05). Compared with the F group, liver glycogen contents increase signifieantly in both FA group and FAP group (p<0.05). Hepatic PK activities increased in the FA, FP and FAP groups (p<0.05). Hepatic G-6-Pase activities decreased significantly in both FA group and FAP group (p<0.05). G-6-PDHase activity decreased in the FA group significantly (p<0.05). Hepatic CAT activity increased significantly in the FA group (p<0.05). Hepatic GSH-Px activity increased significantly in the FAP group (p<0.05). The SFA percentage of in liver TFA decreased significantly in the FAPgroup (p<0.05), while the percentage of PUFA increased signifieantly in FA group (p<0.05). The C18:1 percentages in liver TFA decreased significantly in the FA group and FAP group (p<0.05). The C18:2 n-6 percentages increased significantly in the FA, FP and FAP groups (p<0.05). Additionally, The percentages of C15:0, C17:l and C22:1 fatty acids increased significantly in the FAP group (p<0.05).5) Young healthy subjects were asked to ingest five rice vinegar powder tablets (containing 2.5 g rice vinegar powder) daily for 16 weeks. Compared with the control group (without vinegar powder tablets intake), serum total protein, albumin, and uric acid levels increased significantly in the vinegar powder group. However, all hepatic and renal parameters fluctuated within normal physiological range. The changes in serum total protein, albumin and uric acid were also within the clinically normal ranges and were not clinically relevant.Dietary acetic acid supplement showed significant anti-hyperlipidemia effect. The concentration of 0.2 % showed the best effect. Dietary acetic acid improved insulin sensitivity due to affecting TG metabolism in liver by increasing the activity of hepatic total lipase. Both acetic acid and the total nonvolatile components in vinegar could interfere with the development of insulin resistance induced by high fructose diet due to decreasing TG synthesis and NEFA content in liver, increasing C18:1 but decreasing C 18:2 n-6 fatty acid percentage in liver TEA. However, acetic acid could also exert its effect by abbreviation hepatic oxidative stress and inhibition hepatic glyconeogenesis. Daily intake of 2.5 g rice vinegar powder was safe to healthy people. For its increase effect on serum uric acid level, rice vinegar powder should be cautious for patients with hyperuricemia.更多还原