基于代谢组学探讨高果糖对幼年大鼠生殖及子代的影响与淫羊藿苷的干预作用

发布时间：2018-07-17 03:02

【摘要】：背景:过去几十年来,高果糖或高果糖玉米糖浆的消费量显著增加。果糖消费与代谢综合征及其合并症相关联,果糖被作为肥胖症流行的潜在因素。然而,尽管含有果糖的食品和饮料的广泛消费和肥胖的发病率上升,但很少注意果糖消耗对幼年期大鼠和对后代的长期影响,几乎没有研究关注幼年期雄鼠果糖的摄入对雄性生殖及子代的长期影响。近年,男性不育的发生率越来越高。人类饮食结构的大改变,果糖的过量摄入,是不是导致男性精子质量下降的因素呢?果糖对精子的影响,是否会遗传给子代呢?对果糖摄入的不良影响的干预,目前研究较多的是牛磺酸、白藜芦醇、沙丁鱼蛋白的补充,但缺乏有效的干预策略的数据。不育,中医认为与先天肾精不足有关,淫羊蕾苷具有补充肾阳,改善勃起功能等作用。代谢组学是通过对组群指标进行分析,以高通量检测和数据处理,研究生物体或组织细胞系统整体水平的动态变化的学科。简单地说,代谢组能够反映机体是处于正常状态还是病理状态以及何种病理状态。这种整体性、系统性的特点与中医药理论之“整体观念”相吻合。本研究拟探讨高果糖饮食对幼年雄性SD大鼠生殖及子代的影响及淫羊藿苷的干预作用,并引入代谢组学技术和方法,理论探寻高果糖饮食对幼年雄性SD大鼠生殖及子代影响的客观依据。目的:探讨高果糖饮食对幼年雄性SD大鼠生殖及子代的影响与淫羊藿苷的干预机制研究方法:第一部分,断奶SD大鼠(F0代),分为对照组,果糖喂养组,共喂养8周。喂养结束后,进行雌雄鼠1:1合笼。合笼结束后,处死雄鼠,检测精液常规;观察雌鼠妊娠率,产仔数目,子代存活率、性别比、体重变化。F1代观察至成年,进行合笼。合笼结束后,处死雄鼠,检测精液常规;观察雌鼠妊娠率,产仔数目,子代存活率、性别比、体重变化。F2代雄鼠观察至成年,处死检测精液常规。第二部分,实验设计同第一部分第一节,获得F0血清、精浆,进行代谢组学检测,发现差异代谢物。第三部分,断奶SD大鼠(F0代),分为对照组,果糖喂养组,淫羊藿苷低剂量组,淫羊藿苷高剂量组。共喂养8周。喂养结束合笼。合笼结束后,处死雄鼠,检测精液常规;观察雌鼠妊娠率,产仔数目,子代存活率、性别比、体重变化。第四部分:实验设计同第三部分。获得F0血清、精浆,进行代谢组学检测,发现差异代谢物。结果:1)高果糖饮食喂养幼年期SD大鼠影响雄鼠体重、血糖、妊娠率;影响F1及F2代体重增长,这种传代影响可能是通过影响精子质量来完成的。2)血清代谢组学分析发现,果糖组血清代谢物丙酮酸、柠檬酸、柠檬酸盐、氧化三甲胺、丙三醇/甘油、甜菜碱、3-羟基丁酸含量显著升高,而乳酸、组氨酸、谷氨酰胺/谷氨酸、高密度脂蛋白含量降低。精浆代谢组学发现:果糖组精浆雌二醇、精胺、亚精胺、2-甲基-3-羟丁酸含量升高。3)淫羊藿苷可改善精子质量,增加子代体重增长,逆转果糖喂养不良影响。4)给予淫羊藿苷干预后,血清中代谢物天冬氨酸、鞘氨醇、异维A酸、组氨酸、谷氨酰胺/谷氨酸含量升高,甲基丙烯酮、3-羟基丁酸、丙酮酸、柠檬酸、柠檬酸盐含量降低。精浆代谢组产物雌二醇、精胺、亚精胺、2-甲基-3-羟丁酸含量降低。结论:幼年期SD雄鼠高果糖饮食影响生殖及子代体重,可能是果糖喂养扰乱了脂质代谢、三羧酸循环、雄激素和雌激素代谢、精胺和亚精胺的合成,导致了精子质量的下降,从而遗传给子代。淫羊藿苷可通过调节脂质代谢、三羧酸循环,降低雌二醇、精胺和亚精胺的浓度,改善高果糖饮食对SD雄鼠及子代的不良影响。
[Abstract]:Background: the consumption of high fructose or high fructose corn syrup has increased significantly over the past several decades. Fructose consumption is associated with metabolic syndrome and its complication. Fructose is a potential factor in obesity epidemic. However, little attention has been paid to fructose consumption despite the widespread consumption of fructose and the increasing incidence of obesity. For the long-term effects of young rats and their offspring, little attention has been paid to the long-term effects of fructose intake on male reproduction and offspring. In recent years, the incidence of male infertility is becoming higher and higher. Whether the effect of sperm can be inherited to the progeny? The intervention on the adverse effects of fructose intake is the supplement of taurine, resveratrol, and sardine protein, but there is no effective intervention strategy. Infertility, Chinese medicine thinks that it is related to innate deficiency of kidney essence, and leprodine can supplement kidney yang and improve erectile function. Metabolomics is a discipline that studies the dynamic changes in the overall level of the organism or tissue cell system by analyzing the group index, using high throughput testing and data processing. In simple terms, the metabolic group can reflect the body's normal state, the pathological state and the pathological state. This holistic, systematic feature The effect of high fructose diet on the reproduction and offspring of young male SD rats and the intervention of icariin in young male rats were discussed in this study. The objective basis of the effect of high fructose diet on the growth and offspring of young male SD rats was explored. The effect of high fructose diet on the reproductive and offspring of young male SD rats and the methods of icariin intervention: the first part, weaning SD rats (F0 generation), divided into the control group and the fructose feeding group for 8 weeks. After feeding, the male and female rats were fed with 1:1 cage. After the cage ended, the male rats were killed and the semen routine was detected; the pregnancy rate of female rats was observed. The number of offspring, the survival rate of the progeny, the sex ratio, the.F1 generation of the body weight and the cage. After the closure of the cage, the male rats were killed and the semen routine was detected. The pregnancy rate, the number of offspring, the survival rate of the offspring, the sex ratio, the body weight change of the male rats were observed to the year of the male rats of the.F2 generation, and the second part of the experiment was designed and the first part was designed with the first part. In the first section, F0 serum, seminal plasma, metabonomics were detected and the difference metabolites were detected. The third part, weaning SD rats (F0 generation), divided into control group, fructose feeding group, icariin low dose group, icariin high dose group, high dose group of icariin, feeding after feeding the cage. After closing the cage, the male rats were sacrificed to test the semen routine; observed the pregnancy of female rats Rate, litter size, subgeneration survival, sex ratio, body weight change. Fourth part: experimental design and third parts. F0 serum, seminal plasma, metabolomics, differential metabolites were detected. Results: 1) high fructose diet of young SD rats affected male rats weight, blood sugar, pregnancy rate; influence of F1 and F2 generation weight growth, this passage effect could be The serum metabolomics analysis of.2, which can be accomplished through the effect of sperm quality, found that the serum metabolite pyruvic acid, citric acid, citrate, trimethylamine, glycerol / glycerol, betaine, 3- hydroxybutyric acid increased significantly, while lactic acid, histidine, glutamine / glutamic acid, high density lipoprotein content decreased. It was found that oestradiol, spermine, spermidine, 2- methyl -3- hydroxybutyric acid increased.3 in fructose group, icariin could improve sperm quality, increase the growth of progeny weight, reverse the effect of.4 on fructose feeding, and give the prognosis of icariin, serum metabolite aspartic acid, sphingosine, isovitamin A acid, histidine, glutamine / glutamic acid content The content of methylacroone, 3- hydroxybutyric acid, pyruvic acid, citric acid, citrate and citrate decreased. The content of estradiol, spermine, spermidine and 2- methyl -3- hydroxybutyric acid in the seminal plasma group decreased. Conclusion: the high fructose diet of young SD male rats affected the reproductive and offspring body weight, and it could be that fructose feeding disrupted the lipid metabolism, the three carboxylic acid cycle, androgens The synthesis of estrogen metabolism, spermine and spermidine leads to the decrease of sperm quality, thus hereditary to the progeny. Icariin can regulate the lipid metabolism, three carboxylic acid cycle, reduce the concentration of estradiol, spermine and spermidine, and improve the adverse effects of high fructose diet on SD male rats and offspring.
【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R589

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