【摘要】：背景:過(guò)去幾十年來(lái),高果糖或高果糖玉米糖漿的消費(fèi)量顯著增加。果糖消費(fèi)與代謝綜合征及其合并癥相關(guān)聯(lián),果糖被作為肥胖癥流行的潛在因素。然而,盡管含有果糖的食品和飲料的廣泛消費(fèi)和肥胖的發(fā)病率上升,但很少注意果糖消耗對(duì)幼年期大鼠和對(duì)后代的長(zhǎng)期影響,幾乎沒(méi)有研究關(guān)注幼年期雄鼠果糖的攝入對(duì)雄性生殖及子代的長(zhǎng)期影響。近年,男性不育的發(fā)生率越來(lái)越高。人類(lèi)飲食結(jié)構(gòu)的大改變,果糖的過(guò)量攝入,是不是導(dǎo)致男性精子質(zhì)量下降的因素呢?果糖對(duì)精子的影響,是否會(huì)遺傳給子代呢?對(duì)果糖攝入的不良影響的干預(yù),目前研究較多的是�；撬�、白藜蘆醇、沙丁魚(yú)蛋白的補(bǔ)充,但缺乏有效的干預(yù)策略的數(shù)據(jù)。不育,中醫(yī)認(rèn)為與先天腎精不足有關(guān),淫羊蕾苷具有補(bǔ)充腎陽(yáng),改善勃起功能等作用。代謝組學(xué)是通過(guò)對(duì)組群指標(biāo)進(jìn)行分析,以高通量檢測(cè)和數(shù)據(jù)處理,研究生物體或組織細(xì)胞系統(tǒng)整體水平的動(dòng)態(tài)變化的學(xué)科。簡(jiǎn)單地說(shuō),代謝組能夠反映機(jī)體是處于正常狀態(tài)還是病理狀態(tài)以及何種病理狀態(tài)。這種整體性、系統(tǒng)性的特點(diǎn)與中醫(yī)藥理論之“整體觀(guān)念”相吻合。本研究擬探討高果糖飲食對(duì)幼年雄性SD大鼠生殖及子代的影響及淫羊藿苷的干預(yù)作用,并引入代謝組學(xué)技術(shù)和方法,理論探尋高果糖飲食對(duì)幼年雄性SD大鼠生殖及子代影響的客觀(guān)依據(jù)。目的:探討高果糖飲食對(duì)幼年雄性SD大鼠生殖及子代的影響與淫羊藿苷的干預(yù)機(jī)制研究方法:第一部分,斷奶SD大鼠(F0代),分為對(duì)照組,果糖喂養(yǎng)組,共喂養(yǎng)8周。喂養(yǎng)結(jié)束后,進(jìn)行雌雄鼠1:1合籠。合籠結(jié)束后,處死雄鼠,檢測(cè)精液常規(guī);觀(guān)察雌鼠妊娠率,產(chǎn)仔數(shù)目,子代存活率、性別比、體重變化。F1代觀(guān)察至成年,進(jìn)行合籠。合籠結(jié)束后,處死雄鼠,檢測(cè)精液常規(guī);觀(guān)察雌鼠妊娠率,產(chǎn)仔數(shù)目,子代存活率、性別比、體重變化。F2代雄鼠觀(guān)察至成年,處死檢測(cè)精液常規(guī)。第二部分,實(shí)驗(yàn)設(shè)計(jì)同第一部分第一節(jié),獲得F0血清、精漿,進(jìn)行代謝組學(xué)檢測(cè),發(fā)現(xiàn)差異代謝物。第三部分,斷奶SD大鼠(F0代),分為對(duì)照組,果糖喂養(yǎng)組,淫羊藿苷低劑量組,淫羊藿苷高劑量組。共喂養(yǎng)8周。喂養(yǎng)結(jié)束合籠。合籠結(jié)束后,處死雄鼠,檢測(cè)精液常規(guī);觀(guān)察雌鼠妊娠率,產(chǎn)仔數(shù)目,子代存活率、性別比、體重變化。第四部分:實(shí)驗(yàn)設(shè)計(jì)同第三部分。獲得F0血清、精漿,進(jìn)行代謝組學(xué)檢測(cè),發(fā)現(xiàn)差異代謝物。結(jié)果:1)高果糖飲食喂養(yǎng)幼年期SD大鼠影響雄鼠體重、血糖、妊娠率;影響F1及F2代體重增長(zhǎng),這種傳代影響可能是通過(guò)影響精子質(zhì)量來(lái)完成的。2)血清代謝組學(xué)分析發(fā)現(xiàn),果糖組血清代謝物丙酮酸、檸檬酸、檸檬酸鹽、氧化三甲胺、丙三醇/甘油、甜菜堿、3-羥基丁酸含量顯著升高,而乳酸、組氨酸、谷氨酰胺/谷氨酸、高密度脂蛋白含量降低。精漿代謝組學(xué)發(fā)現(xiàn):果糖組精漿雌二醇、精胺、亞精胺、2-甲基-3-羥丁酸含量升高。3)淫羊藿苷可改善精子質(zhì)量,增加子代體重增長(zhǎng),逆轉(zhuǎn)果糖喂養(yǎng)不良影響。4)給予淫羊藿苷干預(yù)后,血清中代謝物天冬氨酸、鞘氨醇、異維A酸、組氨酸、谷氨酰胺/谷氨酸含量升高,甲基丙烯酮、3-羥基丁酸、丙酮酸、檸檬酸、檸檬酸鹽含量降低。精漿代謝組產(chǎn)物雌二醇、精胺、亞精胺、2-甲基-3-羥丁酸含量降低。結(jié)論:幼年期SD雄鼠高果糖飲食影響生殖及子代體重,可能是果糖喂養(yǎng)擾亂了脂質(zhì)代謝、三羧酸循環(huán)、雄激素和雌激素代謝、精胺和亞精胺的合成,導(dǎo)致了精子質(zhì)量的下降,從而遺傳給子代。淫羊藿苷可通過(guò)調(diào)節(jié)脂質(zhì)代謝、三羧酸循環(huán),降低雌二醇、精胺和亞精胺的濃度,改善高果糖飲食對(duì)SD雄鼠及子代的不良影響。
[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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R589

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