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番茄红素调节大鼠血脂的剂量效应研究
The Dose-effect of Lycopene on Regulating Blood Lipids in Rats
【作者】 王浩;
【导师】 胡敏予;
【作者基本信息】 中南大学 , 营养与食品卫生, 2009, 硕士
【摘要】 目的:研究番茄红素调节大鼠血脂的剂量效应,为对番茄红素的深入研究以及应用提供实验依据。方法:纯种健康雄性Sprague-Dawley大鼠64只,体重200±10g,基础饲料适应性饲养1周,空腹称重,取尾血测定血清TC,根据血清TC水平、体重随机分为8组,每组8只:空白对照组(A组),基础饲料饲养;模型组(B组)、阳性药物对照组(C组)及番茄红素剂量组(D、E、F、G、H组),高脂饲料饲养。饲养1周后,各组大鼠灌胃处理:A组和B组给予溶剂1%CMC-Na,C组10mg·kg·bw-1·d-1氟伐他汀钠,D、E、F、G、H组分别给予4.4、11、22、44、110 mg·kg·bw-1·d-1番茄红素;氟伐他汀钠和番茄红素均以1%CMC-Na为溶剂,各组动物灌胃容量为1mg·kgbw-1·d-1。0周和实验第1、2、3周末检测血清TC、TG、LDL-C、HDL-C、SOD、MDA含量。实验结束,1%戊巴比妥那麻醉大鼠,分离出主动脉弓至髂动脉分叉处主动脉,取主动脉弓起始段0.5cm进行石蜡包埋,HE染色,光镜下观察主动脉管壁形态学变化;摘取心脏、肝脏、肾脏和睾丸,分离周围组织后称重,计算各脏器指数。结果:1.高脂饲料饲养1周后,各组大鼠血清TC、TG、LDL-C含量明显高于空白对照组(A组)(P<0.05)。随实验时间延长,模型组(B组)血清TC、TG、LDL-C含量持续升高,至实验末期,相对B组实验开始时分别升高13.56、4.51、6.65倍;光镜下观察病理切片显示动脉管腔不规则,内膜明显增厚,管壁可见弥漫性隆起,在内膜和内膜下有大量泡沫细胞堆积,部分已达到中膜层,中膜浅层结构紊乱。2.经重复测量方差分析,不同实验期不同组之间大鼠血清TC变化趋势不同(F=5265.297,P=0.000);经血清TC含量变化拟合曲线分析,实验第2(R2=0.649,P=0.000)、3(R2=0.634,P=0.000)周,番茄红素各剂量组降低血清TC水平呈现明显二次曲线关系。经重复测量方差分析,不同实验期不同组之间大鼠血清TG变化趋势不同(F=391.972,P=0.000);经血清TG含量变化拟合曲线分析,实验第2(R2=0.900,P=0.000)、3(R2=0.926,P=0.000)周,番茄红素各剂量组降低血清TG水平呈现明显的二次曲线关系。经重复测量方差分析,不同实验期不同组之间大鼠血清LDL-C变化趋势不同(F=2645.165,P=0.000);经血清LDL-C含量变化拟合曲线分析,实验第2(R2=0.463,P=0.000)、3(R2=0.717,P=0.000)周番茄红素各剂量组降低大鼠血清LDL-C水平呈现明显的二次曲线关系。整个实验期间,番茄红素各剂量组及氟伐他汀钠组对血清HDL-C无明显作用(P>0.05)。光镜下观察44mg·kg bw-1·d-1、110 mg·kg bw-1·d-1剂量组主动脉病理切片显示:大部分内膜完整,内膜残存少量泡沫细胞,未见纤维组织增生,两剂量组病理改变与氟伐他汀钠组病理改变接近。3.重复测量方差分析结果显示,不同实验期不同组之间大鼠血清SOD变化趋势不同(F=7014.837,P=0.000),经血清SOD含量变化拟合曲线分析,实验第2(R2=0.876,P=0.000)、3(R2=0.946,P=0.000)周番茄红素各剂量组升高血清SOD水平呈现明显的二次曲线关系。不同实验期不同组之间大鼠血清MDA变化趋势不同(F=1844.478,P=0.000),经血清MDA含量变化拟合曲线分析,实验第2(R2=0.870,P=0.000)、3(R2=0.876,P=0.000)周番茄红素各剂量组降低血清MDA水平呈现明显的二次方曲线关系。结论:1.参照Deepa的快速造模方法,高脂饲料饲养1周后,形成高血脂模型,方法快速简便,实验结束,模型组大鼠主动脉病理切片光镜下观察,管腔不规则,内膜明显增厚,管壁可见弥漫性隆起,在内膜和内膜下有大量泡沫细胞堆积,部分已达到中膜层,中膜浅层结构紊乱。2.番茄红素在剂量为11~44 mg·kg·bw-1·d-1范围内,降低血清TC水平呈现剂量效应关系;番茄红素在剂量为4.4~22 mg·kg·bw-1·d-1范围内,降低血清TG水平呈现剂量效应关系;番茄红素在剂量为4.4~44 mg·kgbw-1·d-1范围内,降低血清LDL-C水平呈现剂量效应关系。3.番茄红素在剂量为4.4~44 mg·kg·bw-1·d-1范围内,降低血清MDA水平,升高血清SOD水平呈现剂量效应关系。
【Abstract】 Objective:In order to study the dose-effect on lycopene regulation of plasma lipid in hyperlipidemia rats;to provide the evidence for the exploitation of lycopene and utilizion in body and research further.Methord:According to the level of serum total cholesterol and weight, Sixty-four adult male SD rats were divided randomly into eight groups: normal control,fed by normal feed;hyperlipidemia group:fed by CCT diet; positive control group:fed by CCT diet plus 10 mg·kg·b/w·d fluvastatin sodium;dose of lycopene groups:fed by CCT diet plus 4.4,11,22,44,110 mg·kg·b/w·d lycopene;intragastric administration.The level of serum total cholesterol,total triglyceride,low-density lipoprotein cholesterol, high-density lipoprotein cholesterol,SOD,and MDA were measured.At the end of the reasrch,the rats were narcosisd by tuina.Morphologic aorta atherosclerosis was observed by HE staining methods.Select morph,liver, kidney,testicle and weight them to compute the index number.Result:1.Fed by CCT diet one week,groups B rats of serum lipids were higher than group A(P<0.05).As the experimental session extended,the serum TC,TG,LDL-C of group B were become higher gradually,at the end of the experiment,TC,TG,LDL-C were 13.56,4.51,6.65 times than the start of the group B(P<0.05);the pathological section showed that endomembrane was thicked obviously,vessel wall oncoidesd,foam cells heaped up,some reached tunica media,the structure lamina superficialis of tunica media disordered.2.By the multivariate analysis of variance of repeated measure,the data showed that different doses of lycopene at different experiment stage had different degree of regulation to TC(F=5265.297,P=0.000).By curue fitting analysis,the result of week 2(R2=0.649,P=0.000) and 3(R2=0.634,P=0.000) showd that as the increasing doses of lycopene,they could reduce the role of serum TC,and showd the obviously relationship of square plot;By the multivariate analysis of variance of repeated measure,the data showed that different doses of lycopene at different experiment stage had different degree of regulation to TG(F=391.972,P=0.000).By curue fitting analysis,the result of week 2(R2=0.900,P=0.000) and 3(R2=0.926,P=0.000) showd that as the increasing doses of lycopene,they could reduce the role of serum TG,and showd the obviously relationship of square plot;By the multivariate analysis of variance of repeated measure,the data showed that different doses of lycopene at different experiment stage had different degree of regulation to LDL-C(F=2645.165,P=0.000).By curue fitting analysis,the result of week 2(R2=0.463,P=0.000)and 3(R2=0.717,P=0.000)showd that as the increasing doses of lycopene,they could reduce the role of serum LDL-C,and showd the obviously relationship of square plot;There were no significant effect to HDL-C on any dose of Lycopene(P>0.05).The dose of lycopene in the 44,110 mg·kg·b/w·d were the same as group C:the bulk of endomemb-rane was integrity,foam cells disappeared,there was not fibro-plasia.3.By the multivariate analysis of variance of repeated measure,the data showed that different doses of lycopene at different experiment stage had different degree of regulation to SOD(F=7014.837,P=0.000),By curue fitting analysis,the result of week 2(R2=0.876,P=0.000) and 3(R2=0.946, P=0.000) showd that as the increasing doses of lycopene,they could increase the role of serum SOD,and showd the obviously relationship of square plot; By the multivariate analysis of variance of repeated measure,the data showed that different doses of lycopene at different experiment stage had different degree of regulation to MDA(F=1844.478,P=0.000),By curue fitting analysis,the result of week 2(R2=0.870,P=0.000) and 3(R2=0.876,P=0.000) showd that as the increasing doses of lycopene,they could reduce the role of serum SOD,and showd the obviously relationship of square plot.Conclusion:1.By the methord of Deepa,fed by CCT diet one week,the rats became hyperlipemia,the methord was easy and quickly,at the end of the experiment groups B hepathological section showed that endomembrane was thicked obviously,vessel wall oncoidesd,foam cells heaped up,some reached tunica media,the structure lamina superficialis of tunica media disordered.2.Between the scope of 11~44 mg·kg bw-1·d-1,lycopene reduced TC showd obviously dose-effect;Between the scope of 4.4~22 mg·kg bw-1·d-1, lycopene reduced TG showd obviously dose-effect;Between the scope of 4.4~44 mg·kg bw-1·d-1,lycopene reduced LDL-C showd obviously dose-effect;3.Between the scope of 4.4~44mg·kg bw-1·d-1,lycopene reduced MDA, increased SOD showd obviously dose-effect.