动物营养学报    2018, Vol. 30 Issue (10): 3968-3975    PDF    
瘤胃保护性色氨酸饲粮中添加亚叶酸钙对绵羊血浆色氨酸、犬尿氨酸和褪黑素含量的影响
王根, 陈晖, 赵芳, 高超, 赵国栋, 李晓斌, 马晨, 杨开伦     
新疆农业大学动物科学学院, 新疆肉乳用草食动物营养重点实验室, 乌鲁木齐 830052
摘要: 本试验在瘤胃保护性色氨酸(RPTrp)饲粮中添加2种剂量的亚叶酸钙(CF),研究其对绵羊血浆色氨酸(Trp)、犬尿氨酸(Kyn)和褪黑素(MT)含量的影响,旨在探究调控反刍动物体内MT合成的方法。试验选取(3.0±0.5)岁、平均体重(64.45±3.48)kg的健康萨福克绵羊15只,随机分为3组,每组5只,分别为对照组、试验Ⅰ组和试验Ⅱ组。每天每只羊精料补充料饲喂量为12 g/kg BW,玉米青贮为1.8 kg,RPTrp为222.2 mg/kg BW,自由采食混合干草,在此基础上,试验Ⅰ组添加50 mg的CF、试验Ⅱ组添加100 mg的CF,进行15 d的饲养试验。结果表明:1)上午饲喂后0~12.0 h期间,各组间血浆Trp、Kyn含量差异均不显著(P>0.05);在上午饲喂后6.0、8.0 h时,试验组血浆Trp含量有降低的趋势(P=0.087 2、P=0.053 1);在上午饲喂后4.5、6.0、8.0、10.0 h时,试验组血浆Kyn含量也有降低的趋势(P=0.094 8、P=0.066 7、P=0.090 9、P=0.054 2)。2)上午饲喂后4.5、8.0 h时,试验组血浆5-羟色胺(5-HT)含量与对照组相比有增加的趋势(P=0.080 7、P=0.054 1),在上午饲喂后10.0 h时,试验组极显著升高(P=0.005 7);上午饲喂后6.0、8.0 h时,试验组MT含量也有增加的趋势(P=0.089 0、P=0.070 4),在上午饲喂后10.0 h时,试验组极显著高于对照组(P=0.000 2)。3)上午饲喂前0 h,与对照组相比,试验Ⅱ组血浆总抗氧化能力、谷胱甘肽过氧化物酶活性均显著提高(P < 0.05),丙二醛含量显著降低(P < 0.05),试验Ⅰ组血浆总抗氧化能力也显著提高(P < 0.05)。因此,在RPTrp(222.2 mg/kg·BW)饲粮中每天每只绵羊添加50或100 mg的CF,在上午饲喂后4.5~10.0 h期间有降低血浆Kyn含量的趋势,对血浆Trp、5-HT、MT含量整体没有显著影响,但可提高绵羊血浆抗氧化能力。
关键词: 绵羊     瘤胃保护性色氨酸     亚叶酸钙     犬尿氨酸     褪黑素    
Effects of Adding Calcium Folate in Rumen Protected Trytophan Diets on Plasma Tryptophan, Kynurenine and Melatonin Contents in Sheep
WANG Gen, CHEN Hui, ZHAO Fang, GAO Chao, ZHAO Guodong, LI Xiaobin, MA Chen, YANG Kailun     
Xinjiang Agricultural University, Xinjiang Key Laboratory of Meat & Milk Production Herbivore Nutrition, Urumqi 830052, China
Abstract: The objective of this study was to explore the method of regulating the synthesis of melatonin (MT) in ruminants by detecting the effects of adding two doses of calcium folate (CF) in rumen protected trytophan (RPTrp) diets on plasma tryptophan (Trp), kynurenine (Kyn) and MT contents in sheep. Fifteen Suffolk sheep aged (3.0±0.5) years, with an average body weight (64.45±2.41) kg were divided into 3 groups (5 in each group):control group, trail group Ⅰ and trial group Ⅱ. The amount of feed (per day per sheep) were 12 g/kg BW of concentrate supplement, 1.8 kg corn silage, 222.2 mg/kg BW of RPTrp, and mixed hay was fed ad libitum. On the basis of this, sheep in trail group Ⅰ and trial group Ⅱ were fed 50 and 100 mg CF per sheep per day, respectively. The results showed as follows:1) there was no significant difference in plasma Trp and Kyn contents among groups during 0 to 12.0 h after feeding in the morning (P>0.05), but plasma Trp content in trial groups reduced at 6.0 and 8.0 h after feeding in the morning (P=0.087 2, P=0.053 1). Plasma Kyn content in the plasma of trial groups reduced too at 4.5, 6.0, 8.0 and 10.0 h after feeding in the morning (P=0.094 8, P=0.066 7, P=0.090 9, P=0.0542). 2) At 4.5 and 8.0 h after feeding in the morning, plasma 5-hydroxytryptamin (5-HT) content in trail groups increased compared with the control group (P=0.080 7, P=0.054 1). At 10.0 h after feeding in the morning, plasma 5-HT content in trail groups significantly increased (P=0.005 7). At 6.0 and 8.0 h after feeding in the morning, plasma MT content in trail groups also increased (P=0.089 0, P=0.070 4), and it was significantly higher at 10.0 h after feeding in the morning than that in the control group (P=0.000 2). 3) Compared with the control group, the plasma total antioxidant capacity and glutathione peroxidase activity in trail group Ⅱ were significantly increased (P < 0.05), malonaldehyde content was significantly decreased (P < 0.05), and total antioxidant capacity in trail group Ⅰ was also significantly improved (P < 0.05). In conclusion, the RPTrp (222.2 mg/kg BW) diets with 50 or 100 mg CF per sheep per day has the tendency of reducing plasma Kyn content from 4.5 to 10.0 h after feeding in the morning, has no significant effect on plasma Trp, 5-HT, MT contents, but can improve the plasma antioxidant capacity of sheep.
Key words: sheep     rumen protected tryptophan     calcium folate     kynurenine     melatonin    

哺乳动物体内褪黑素(melatonin,MT)是主要由松果体合成和分泌的一种吲哚类激素,广泛分布在很多器官、组织和细胞中[1-2]。研究显示,MT可促进绵羊卵母细胞成熟[3]、维持精子功能[4]、促进胚胎发育[5]和提高机体的抗氧化能力[6],因此适当提高血浆MT含量可能对绵羊生殖和机体健康具有重要的意义。色氨酸(tryptophan,Trp)作为动物体内合成MT的前体物质,在体内经羟化、脱羧、乙酰化和甲基化形成MT。本实验室前期研究表明,补喂瘤胃保护性色氨酸(rumen protected tryptophan,RPTrp)可提高绵羊血浆总Trp和游离Trp含量,同时犬尿氨酸(kynurenine,Kyn)含量也升高。提高Trp转化为MT合成量首先要提高5-羟色胺(5-hydroxytryptamine,5-HT)合成量,而四氢生物蝶呤(tetrahydrobiopterin,BH4)是Trp合成5-HT的关键酶色氨酸羟化酶(tryptophan hydroxylase,TPH)的辅酶[7]。亚叶酸钙(calcium folinate,CF)是叶酸的衍生物,经吸收后可直接提供叶酸在体内的活化形式,具有稳定BH4的作用[8-9]。因此,本试验选择绵羊为试验动物,在RPTrp饲粮中添加CF,探究CF对调控反刍动物体内MT合成的影响。

1 材料与方法 1.1 试验时间与地点

试验于2017年7月30日至2017年8月14日在新疆惠康畜牧生物科技有限公司羊场、自然光照条件下进行。采集血样当天日出时间为07:12,日落时间为21:15,昼长14.03 h。

1.2 试验动物

选择(3.0±0.5)岁、平均体重(64.45±3.48) kg的健康萨福克绵羊15只。

1.3 试验设计

将15只萨福克绵羊随机分为3组,每组5只,分别为对照组、试验Ⅰ组和试验Ⅱ组。所有试验羊只饲喂同一营养水平精料补充料(购自新疆天康畜牧生物技术股份有限公司),每天每只羊精料补充料饲喂量为12 g/kg BW、RPTrp(购自北京亚禾营养高新技术有限公司,Trp含量≥45%,过瘤胃率≥85%)为222.2 mg/kg BW(补喂量参考Itabashi等[10]的研究结果)、玉米青贮为1.8 kg,混合干草(苜蓿:麦秸=1 : 1)为自由采食,自由饮水,在此基础上,试验Ⅰ组每天每只羊添加50 mg的CF(购自上海柯维化学技术有限公司),试验Ⅱ组每天每只羊添加100 mg的CF(添加量参考Ravaud等[11]的研究结果)。精料补充料组成及营养水平见表 1,玉米青贮、苜蓿和麦秸的营养水平见表 2

表 1 精料补充料组成及营养水平(干物质基础) Table 1 Composition and nutrition levels of the concentrate supplement (DM basis)
表 2 玉米青贮、苜蓿干草、麦秸的营养水平(干物质基础) Table 2 Nutrition levels of corn silage, alfalfa and wheat straw (DM basis)
1.4 饲养管理

试验羊只单栏位饲养,每天每只羊的RPTrp、CF、精料补充料和玉米青贮平均分成2份,分别于08:00、20:00饲喂。为保证RPTrp和CF采食完全,先将RPTrp、CF与50 g精料补充料混匀后饲喂,待绵羊采食完毕后再投喂剩余精料补充料、玉米青贮,自由采食混合干草和饮水。根据试验羊场的饲养管理规定,定期打扫圈舍。

1.5 样品的采集与处理

于试验的第16天采集血样,采集时间点为上午饲喂前0 h(07:30)、饲喂后1.5、3.0、4.5、6.0、8.0、10.0、12.0 h,通过颈静脉采集血液至肝素钠抗凝采血管中,3 500 r/min离心15 min制备血浆,分装至1.5 mL Eppendorf管中,标记后-20 ℃冰箱中冷冻保存。

1.6 指标的测定

采用高效液相色谱法测定血浆Trp、Kyn含量[12]。采用酶联免疫吸附法测定血浆5-HT、MT含量;上午饲喂前0 h血浆总抗氧化能力(T-AOC),谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量采用比色法测定,样品均送至北京华英生物技术研究所进行检测。

1.7 数据处理

采用SAS 8.0统计软件的ANOVA进行单因素方差分析,差异显著则用Duncan氏法进行多重比较。用P≤0.01、P≤0.05和0.05<P<0.10分别作为差异极显著、差异显著和有差异趋势的判断标准。

2 结果 2.1 RPTrp饲粮中添加CF对绵羊血浆Trp含量的影响

表 3可知,上午饲喂后0~12.0 h期间,各组间绵羊血浆Trp含量差异均不显著(P>0.05),变化趋势基本一致;在上午饲喂后6.0和8.0 h时,与对照组相比,试验组血浆Trp含量有降低的趋势(P=0.087 2、P=0.053 1)。

表 3 RPTrp饲粮中添加CF对绵羊血浆Trp含量的影响 Table 3 Effects of adding CF in RPTrp diets on plasma Trp content in sheep (n=5)
2.2 RPTrp饲粮中添加CF对绵羊血浆Kyn含量的影响

表 4可知,上午饲喂后0~12.0 h期间,各组绵羊血浆Kyn含量无显著性差异(P>0.05),其中在上午饲喂后4.5~10.0 h期间,与对照组相比,试验组血浆Kyn含量有降低的趋势(P=0.094 8、P=0.066 7、P=0.090 9、P=0.054 2)。

表 4 RPTrp饲粮中添加CF对绵羊血浆Kyn含量的影响 Table 4 Effects of adding CF in RPTrp diets on plasma Kyn content in sheep (n=5)
2.3 RPTrp饲粮中添加CF对绵羊血浆5-HT含量的影响

表 5可知,上午饲喂后0~8.0 h期间,与对照组相比,试验组绵羊血浆5-HT含量均有所提高,各组间变化趋势相似,但各组间差异不显著(P>0.05);其中在上午饲喂后4.5和8.0 h时,试验组血浆5-HT含量有增加的趋势(P=0.080 7、P=0.054 1);在上午饲喂后10.0 h时,试验组极显著高于对照组(P=0.005 7),试验组间差异不显著(P>0.05)。

表 5 RPTrp饲粮中添加CF对绵羊血浆5-HT含量的影响 Table 5 Effects of adding CF in RPTrp diets on plasma 5-HT content in sheep (n=5)
2.4 RPTrp饲粮中添加CF对绵羊血浆MT含量的影响

表 6可知,上午饲喂后0~8.0 h期间,各组间绵羊血浆MT含量差异不显著(P>0.05),但在上午饲喂后6.0和8.0 h时,试验组MT含量有增加的趋势(P=0.089 0、P=0.070 4)。上午饲喂后8.0~10.0 h期间,对照组绵羊血浆MT含量呈下降趋势,上午饲喂后10.0 h时为白天含量最小值,而试验组呈上升趋势,上午饲喂后10.0 h时极显著高于对照组(P=0.000 2)。

表 6 RPTrp饲粮中添加CF对绵羊血浆MT含量的影响 Table 6 Effects of adding CF in RPTrp diets on plasma MT content in sheep (n=5)
2.5 RPTrp饲粮中添加CF对绵羊血浆抗氧化能力的影响

表 7可知,上午饲喂前0 h,与对照组相比,试验Ⅱ组绵羊血浆T-AOC、GSH-Px活性显著提高(P<0.05),MDA含量显著降低(P<0.05),试验Ⅰ组T-AOC也显著提高(P<0.05),但试验Ⅰ组血浆GSH-Px活性、MDA含量与对照组差异不显著(P>0.05)。各组间血浆SOD活性无显著性差异(P>0.05)。

表 7 RPTrp饲粮中添加CF对绵羊血浆抗氧化能力的影响 Table 7 Effects of adding CF in RPTrp diets on plasma antioxidant capacity in sheep (n=5)
3 讨论 3.1 RPTrp饲粮中添加CF对绵羊血浆Trp、Kyn含量的影响

本试验中,上午饲喂后0~12 h期间,各组间绵羊血浆Trp含量无显著性差异,但试验组均低于对照组,且在上午饲喂后6.0和8.0 h时有降低的趋势。研究显示,CF是叶酸的衍生物,具有稳定和促进机体BH4合成的作用[8]。本试验结果可能与添加CF提高了绵羊体内BH4的含量和TPH的活性、促进Trp沿5-HT途径分解为5-羟色氨酸有关。本试验中,上午饲喂后4.5~10.0 h期间,与对照组相比,试验组绵羊血浆Kyn含量有降低的趋势,与血浆Trp含量的变化趋势基本一致。研究表明,动物体内约95%的L-Trp在色氨酸-2, 3双加氧酶(tryptophan-2, 3-dioxygenase,TDO)和吲哚胺-2, 3双加氧酶(indoleamine-2, 3-dioxygenase,IDO)作用下生成Kyn[13]。正常生理情况下,TDO是肝内催化Trp形成Kyn关键酶,活性主要受底物Trp和激素(糖皮质激素和雌激素)水平的影响[14-15],而IDO主要在机体受感染、炎症或应激时肝外组织发挥作用[16]。本试验中,添加CF可能对绵羊肝内TDO活性无显著影响,血浆Kyn含量降低可能与添加CF提高了绵羊体内TPH活性或表达量有关。

3.2 RPTrp饲粮中添加CF对绵羊血浆5-HT、MT含量的影响

本试验中,上午饲喂后0~8.0 h期间,试验组绵羊血浆5-HT含量与对照组相比无显著性升高,但在上午饲喂后4.5和8.0 h时有升高的趋势。研究显示,动物体内TPH主要有2种不同基因编码的亚型TPH1和TPH2。TPH1主要分布在肠嗜铬细胞和松果体中,TPH2主要分布于肠神经系统和中枢神经系统5-HT神经元中[17-19]。在中枢神经系统中,BH4含量并不能使TPH2饱和,因此,直接向脑室注入10 μL浓度为20 nmol/L的BH4或通过微透析灌注BH4的类似物四氢生物蝶呤二盐酸均可显著增加小鼠脑部组织TPH2活性和5-HT含量[20-21]。能否通过提高血浆BH4含量进而提高TPH1活性和血浆5-HT含量还未见报道。本试验结果可能是CF添加量不足或CF在瘤胃中降解而导致,对TPH1活性无显著性影响。本试验中CF添加量是参考胃癌患者化疗时口服CF量(90 mg/d)设置[11],目前尚未有CF在反刍动物瘤胃内是否有降解的研究文献,今后的试验可通过增加CF添加量或瘤胃保护性CF进一步验证。本试验结果还可能与绵羊体内TPH表达量有关。如果TPH表达量较低,BH4已使其饱和,通过添加CF增加BH4含量也可能对TPH1活性无显著影响。研究表明,哺乳动物机体超过95%的5-HT分布于胃肠道,主要有肠嗜铬细胞合成[22-23]。本试验中,上午饲喂后10.0 h时,试验组绵羊血浆5-HT含量极显著高于对照组,这可能与添加CF促进了肠嗜铬细胞中TPH1的表达和5-羟色氨酸合成有关。由于本试验未采集绵羊肠黏膜组织,在以后试验中可通过测定绵羊肠黏膜中TPH1含量进一步验证。

研究表明,TPH1不仅是合成5-HT的限速酶,也是合成MT的关键酶[24]。在白天,哺乳动物血浆MT主要来于肠嗜铬细胞[25]。Namboodiri等[26]证实,腹腔注射20或200 mg/kg BW的5-羟色氨酸可显著提高绵羊血浆MT含量。本试验中,上午饲喂后6.0和8.0 h时,试验组绵羊血浆MT含量有增加的趋势,上午饲喂后10.0 h时极显著高于对照组。这可能与添加CF增加了绵羊肠嗜铬细胞中TPH1表达量、提高了血浆5-羟色氨酸含量有关。此外,5-HT既是色氨酸、5-羟色氨酸的转化产物,也是生成MT的前体物质。研究发现,肠嗜铬细胞、肠神经细胞、血小板、肝脏和肾脏广泛存在单胺氧化酶,可将5-HT转化为5-羟吲哚乙酸,最后经尿液排出体外[23, 27-28]。本试验中,上午饲喂后4.5 h时,试验组血浆5-HT含量有增加的趋势,而MT含量并未增加,可能与补喂CF增加了绵羊体内5-羟吲哚乙酸含量有关。在今后的研究中可进一步检测绵羊血浆和尿液中5-羟吲哚乙酸含量,验证RPTrp饲粮中添加不同剂量CF对绵羊血浆5-HT含量的影响。

3.3 RPTrp饲粮中添加CF对绵羊血浆抗氧化能力的影响

本试验中,RPTrp饲粮中添加CF可提高绵羊血浆抗氧化能力。研究表明,叶酸可促进二氢生物喋呤(BH2)向BH4转化,而BH4具有抗氧化的功能[29]。由于CF可直接提供叶酸在体内的活化形式,促进BH2向BH4转化。本试验结果可能与绵羊血浆BH4含量升高有关。此外,本试验结果还可能与绵羊血浆MT含量升高有关,MT是一种有效的抗氧化剂,可减少机体活性氧和活性氮的含量,增加抗氧化酶的表达和活性[6]

4 结论

在RPTrp(222.2 mg/kg BW)饲粮中每天每只绵羊添加50或100 mg的CF,有降低血浆Kyn含量的趋势,对白天血浆Trp、5-HT、MT含量整体没有显著影响,但可提高绵羊血浆抗氧化能力。

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