高脂日粮n-6/n-3脂肪酸比例对小鼠抗氧化、血脂及骨代谢的影响
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摘要
本文主要研究了摄入过量脂肪引起高脂血症及氧化应激,通过油脂中不同n-6、n-3多不饱和脂肪酸(polyunsaturated fatty acid,简称PUFA)、饲粮中α-硫辛酸(Alpha-lipoic acid ,简称LA)不同浓度,对小鼠肝脏脂代谢和脂质过氧化相关基因的影响,以及n-6、n-3配比及添加0.05%LA对小鼠骨代谢的影响。
实验一采用4周龄C57断奶雄性小鼠80只,分为10组,分别饲喂基础日粮(对照)、高脂日粮(添加油脂为猪油,粗脂肪含量21.48%)、高脂日粮中PUFA(粗脂肪含量21.48%)中n-6:n-3比例为5∶1(配比1)和10∶1(配比2),三组高脂日粮中分别添加0,0.05%,0.1%LA(w/w),饲喂6周。观察小鼠抗氧化能力及血脂代谢的变化。结果表明高脂日粮导致小鼠血脂升高,机体的总抗氧化能力(T-AOC)降低。两配比油组可提高小鼠血清超氧化物歧化酶(SOD)及总抗氧化能力,降低血清及肝脏中丙二醛(MDA)含量,改善肝脏抗氧化能力,提高肝脏对脂肪的代谢,降低总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)及动脉粥样硬化指数(AI),提高高密度脂蛋白胆固醇含量(HDL-C),维护机体对脂肪的氧化代谢平衡。其中配比2组改善脂质过氧化及提高机体抗氧化能力效果好于配比1组。添加抗氧化剂硫辛酸后能显著改善机体脂质过氧化产生的负面影响,提高小鼠机体抗氧化能力(P<0.05),改善血脂代谢。添加0.1%LA组效果略好于0.5%组(P>0.05)。添加硫辛酸与配比油同时使用,对机体抗氧化及血脂有较好的改善作用。
小鼠肝脏基因表达芯片分析表明,猪油组肝中脂肪?-氧化过程的酶显著下调,影响机体调节碳水化合物、脂类代谢有关的过氧化物酶体增殖物激活受体(PPARs)显著下调,猪油组添加0.1%LA后PPARs恢复到对照组相当的水平。表明LA对可通过影响脂肪代谢相关调控酶,影响机体的血脂水平。
试验二以高脂日粮(粗脂肪含量21.48%)、3种配比油(配比为5∶1、10∶1和15∶1),其中10∶1和15∶1配比组分别添加硫辛酸含量为0%、0.05%,对48只4周龄昆明种断奶雄性小鼠饲喂6周,考察了骨代谢相关指标的变化。观察到未添加LA时,血浆基质金属蛋白酶-9(MMP-9)在配比油组中含量配比1≈配比2组<配比3组;I型胶原羧基端前肽(PICP)含量为配比1<配比2<配比3;骨钙素(BGP)的含量为配比1>配比2≈配比3;而骨特异性碱性磷酸酶(BALP)含量则极为接近。综上,n-6:n-3为10∶1组对抑制骨吸收及促进骨沉积综合的效果好于5∶1组和15∶1组。
添加0.05%LA后,10∶1和15∶1组中MMP-9含量显著下降,PICP、BGP含量显著上升,接近正常组水平,表明LA对骨代谢有较好的保护和促进作用,但其具体作用机制及作用通道现阶段相关资料较少,有必要进一步深入研究。
Different ratios of the n-6 polyunsaturated fatty acid (PUFA) to n-3 PUFA and different content of Alpha-lipoic acid ( LA ,0.05%, 0.1%) in high fat diet affecting the capability of the antioxidation and blood fat metabolism was investigated; We also studied the change of the gene related to lipid metabolism and the lipid peroxidation in liver of mice. During the second stage, the effect of 3 ratios of mixed oil (5:1, 10:1, 15:1) supplemented with 0.05,01% LA on bone characters of the high fat diet mice was investigated.
C57 male mice were fed for 6 weeks with a high fat diet (21.48% crude fat) in 2 different ratios of mixed oil (ratio1 5:1, ratio2 10:1) and 2 different content of LA (0.05%, 0.1%, w/w) .The results show that high fat intake decreases anti-oxidative ability of mice. However, mixed oil increase the level of SOD, decrease the MDA both in the serum and the liver, thereby increased the T-AOC of the mouse, improved the fat metabolism in the liver, decreased the content of the TC, TG, LDL-C, decrease AI and increase the content of the HDL-C. The ratio 10:1 is better than the ratio 5:1.
When LA was added, the negative effect of the lipid peroxidation was significantly relieved, the capability of the anti-oxidation is increased. The improvement of the 0.05% LA group is significant (P<0.05) , the 0.1% LA group is better than the 0.05% group but not significant.
It was found that enzymes related toβ-lipid oxidation were significantly down-regulated, the PPARs related to the metabolism of carbohydrate and the lipid significantly were down-regulated, when we add 0.1%LA, both of them reduced to control level analysed from gene chip. It showed that the LA could effect the enzymes related to the lipid metabolism, to control the level of the blood lipid of the body.
In the second stage, we fed the KM male mice for 6 weeks with 3 different ratios of mixed oil (ratio 1 5:1, ratio 1 10:1, ratio 1 15:1) content 0.05% LA in high fat diet (21.48% crude fat). The different ratios of mixed oil affect different indexes, and didn’t show the semblable trend. The result of MMP-9 is ratio2 < ratio 1< ratio3; PICP is ratio1 < ratio 2 < ratio3; the result of BGP is ratio1 < ratio 2 < ratio3; the resule of BALP are close.When we add 0.05% LA, the indexes related to the osteoblast changed in a positive way. The index MMP-9 which related to the osteocalst (OC) decreased significantly. It shows that LA has a strong effect in inhibiting the expression of the OC, prevent the bone resorption. But the mechanism needs further researched .
实验一采用4周龄C57断奶雄性小鼠80只,分为10组,分别饲喂基础日粮(对照)、高脂日粮(添加油脂为猪油,粗脂肪含量21.48%)、高脂日粮中PUFA(粗脂肪含量21.48%)中n-6:n-3比例为5∶1(配比1)和10∶1(配比2),三组高脂日粮中分别添加0,0.05%,0.1%LA(w/w),饲喂6周。观察小鼠抗氧化能力及血脂代谢的变化。结果表明高脂日粮导致小鼠血脂升高,机体的总抗氧化能力(T-AOC)降低。两配比油组可提高小鼠血清超氧化物歧化酶(SOD)及总抗氧化能力,降低血清及肝脏中丙二醛(MDA)含量,改善肝脏抗氧化能力,提高肝脏对脂肪的代谢,降低总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)及动脉粥样硬化指数(AI),提高高密度脂蛋白胆固醇含量(HDL-C),维护机体对脂肪的氧化代谢平衡。其中配比2组改善脂质过氧化及提高机体抗氧化能力效果好于配比1组。添加抗氧化剂硫辛酸后能显著改善机体脂质过氧化产生的负面影响,提高小鼠机体抗氧化能力(P<0.05),改善血脂代谢。添加0.1%LA组效果略好于0.5%组(P>0.05)。添加硫辛酸与配比油同时使用,对机体抗氧化及血脂有较好的改善作用。
小鼠肝脏基因表达芯片分析表明,猪油组肝中脂肪?-氧化过程的酶显著下调,影响机体调节碳水化合物、脂类代谢有关的过氧化物酶体增殖物激活受体(PPARs)显著下调,猪油组添加0.1%LA后PPARs恢复到对照组相当的水平。表明LA对可通过影响脂肪代谢相关调控酶,影响机体的血脂水平。
试验二以高脂日粮(粗脂肪含量21.48%)、3种配比油(配比为5∶1、10∶1和15∶1),其中10∶1和15∶1配比组分别添加硫辛酸含量为0%、0.05%,对48只4周龄昆明种断奶雄性小鼠饲喂6周,考察了骨代谢相关指标的变化。观察到未添加LA时,血浆基质金属蛋白酶-9(MMP-9)在配比油组中含量配比1≈配比2组<配比3组;I型胶原羧基端前肽(PICP)含量为配比1<配比2<配比3;骨钙素(BGP)的含量为配比1>配比2≈配比3;而骨特异性碱性磷酸酶(BALP)含量则极为接近。综上,n-6:n-3为10∶1组对抑制骨吸收及促进骨沉积综合的效果好于5∶1组和15∶1组。
添加0.05%LA后,10∶1和15∶1组中MMP-9含量显著下降,PICP、BGP含量显著上升,接近正常组水平,表明LA对骨代谢有较好的保护和促进作用,但其具体作用机制及作用通道现阶段相关资料较少,有必要进一步深入研究。
Different ratios of the n-6 polyunsaturated fatty acid (PUFA) to n-3 PUFA and different content of Alpha-lipoic acid ( LA ,0.05%, 0.1%) in high fat diet affecting the capability of the antioxidation and blood fat metabolism was investigated; We also studied the change of the gene related to lipid metabolism and the lipid peroxidation in liver of mice. During the second stage, the effect of 3 ratios of mixed oil (5:1, 10:1, 15:1) supplemented with 0.05,01% LA on bone characters of the high fat diet mice was investigated.
C57 male mice were fed for 6 weeks with a high fat diet (21.48% crude fat) in 2 different ratios of mixed oil (ratio1 5:1, ratio2 10:1) and 2 different content of LA (0.05%, 0.1%, w/w) .The results show that high fat intake decreases anti-oxidative ability of mice. However, mixed oil increase the level of SOD, decrease the MDA both in the serum and the liver, thereby increased the T-AOC of the mouse, improved the fat metabolism in the liver, decreased the content of the TC, TG, LDL-C, decrease AI and increase the content of the HDL-C. The ratio 10:1 is better than the ratio 5:1.
When LA was added, the negative effect of the lipid peroxidation was significantly relieved, the capability of the anti-oxidation is increased. The improvement of the 0.05% LA group is significant (P<0.05) , the 0.1% LA group is better than the 0.05% group but not significant.
It was found that enzymes related toβ-lipid oxidation were significantly down-regulated, the PPARs related to the metabolism of carbohydrate and the lipid significantly were down-regulated, when we add 0.1%LA, both of them reduced to control level analysed from gene chip. It showed that the LA could effect the enzymes related to the lipid metabolism, to control the level of the blood lipid of the body.
In the second stage, we fed the KM male mice for 6 weeks with 3 different ratios of mixed oil (ratio 1 5:1, ratio 1 10:1, ratio 1 15:1) content 0.05% LA in high fat diet (21.48% crude fat). The different ratios of mixed oil affect different indexes, and didn’t show the semblable trend. The result of MMP-9 is ratio2 < ratio 1< ratio3; PICP is ratio1 < ratio 2 < ratio3; the result of BGP is ratio1 < ratio 2 < ratio3; the resule of BALP are close.When we add 0.05% LA, the indexes related to the osteoblast changed in a positive way. The index MMP-9 which related to the osteocalst (OC) decreased significantly. It shows that LA has a strong effect in inhibiting the expression of the OC, prevent the bone resorption. But the mechanism needs further researched .
引文
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