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Hypocholesterolemic effect based on molecular structure and gene expression

基于分子结构和基因表达的低胆固醇效应

基本信息

批准号：
11670395
负责人：
OGAWA Hiroshi
金额：
$ 2.05万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

First of all, I established RT-PCR method for estimation of hepatic mRNA expression of various proteins involved in lipid metabolism, by using densitograph AE-6915 and lane analyzer system (Atto Corp.Tokyo). The established proteins are apoA-I, apoC-II, apoC-III, apoE, acyl-CoA oxidase (ACO), cholesterol 7 α -hydroxylase, HMG-CoA reductase, microsomal triglyceride transferprotein (MTP), h-TGL, peroxisome proliferator-activated receptor (PPAR) α, acyl-CoA oxidase (ACO) fatty acid synthase (FAS), acyl-CoA synthetase (ACS) and uncoupling protein-2 (UCP-2).Next, I applied the RT-PCR method to elucidation of the lipid-regulating activity of Kabosu-juice residue, quinoa powder and natural oils such as harpseal oil, soybean oil and rapeseed oil, using spontaneously hypertensive rats (SHR) as an animal model.In the Kabosu-juice residue experiment, serum lipids of the experimental group were significantly decreased, which was due to decreases in all lipoprotein fractions. Serum apoA-I, apoA-IV … More and apoE were also significantly decreased, which was mainly due to decreases in the high-density lipoprotein (HDL) fraction. In addition, hepatic apoA-I mRNA expression of the experimental group was markedly decreased.In the natural oil experiment, serum HDL-cholesterol and apoA-I of rapeseed oil group increased significantly compared with the other groups (soybean and harpseal oils), while hepatic apoA-I mRNA expression remained unchanged. In the contrast, serum lipids of harpseal oil group rich in n-3 polyunsaturated fatty acids (PUFA) including DPA (Docosapentaenoic acid) decreased obviously compared with the other groups, which was mostly due to decreases in the all lipoprotein fractions. These changes were associated with significant decreases in serum apoA-I, apoB and hepatic apoA-I mRNA expression, suggesting that harpseal oil may decrease very low-density lipoprotein (VLDL), low-density llipoprotein (LDL) and apoA-I HDL.These effects of harpseal oil may be attributed to n-3 PUFA including DPA.However, it is difficult to discriminate the physiological function of DPA from that of the other n-3 PUFA.On the one hand, anti-oxidative activity of the LDL fraction was significantly low only in the rapeseed group, suggesting that LDL fraction of rapeseed oil group may be less resistant to oxidation.These two experiments indicate that the hypocholesterolemic effect of Kabosu-juice residue and harpseal oil may be mediated by PPAR α. Less

首先，利用日本ATTO公司的AE-6915型光密度仪和LEAN分析仪系统，建立了肝脏脂质代谢相关蛋白基因表达的RT-PCR方法。已建立的蛋白质包括载脂蛋白A-I、载脂蛋白C-II、载脂蛋白C-III、载脂蛋白E、酰基辅酶A氧化酶、胆固醇7α羟基酶、hMG辅酶A还原酶、微粒体甘油三酯转移蛋白、h-甘油三酯、过氧化体增殖物激活受体α、酰基辅酶A氧化酶、酰基辅酶A合成酶和解偶联蛋白-2。以自发性高血压大鼠(SHR)为动物模型，在卡波苏果汁残留实验中，实验组大鼠的血脂水平显著降低，这是由于各脂蛋白组分的降低所致。血清载脂蛋白A-I、载脂蛋白A-IV…More和apoE也显著降低，这主要是由于高密度脂蛋白(HDL)部分的减少。在天然油实验中，菜籽油组大鼠血清高密度脂蛋白-胆固醇和载脂蛋白A-I较其他组(大豆油和海狗油)显著升高，而肝脏载脂蛋白A-I的mRNA表达无明显变化。相反，富含n-3多不饱和脂肪酸(PUFA)包括二十二碳五烯酸(DPA)的海豹油组与其他组相比，血脂明显降低，这主要是由于所有脂蛋白组分的减少。这些变化与血清apoA-I、apoB和肝脏apoA-I基因表达的显著降低有关，提示海狗油可以降低极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)和apoA-I HDL。这些作用可能归因于包括DPA在内的n-3PUFA。然而，很难区分DPA和其他n-3PUFA的生理功能。一方面，只有在菜籽组，低密度脂蛋白组分的抗氧化活性显著低于菜籽组。提示菜籽油组低密度脂蛋白组分的抗氧化性可能较差。这两个实验表明，葛根汁渣和海狗油的降胆固醇作用可能是通过PPARα介导的。较少