RESEARCH PAPER

Regulatory Effects of Terpinen-4-ol on Liver Development, Antioxidant Capacity and Immune Function of Weaned Piglets under Immune Stress Induced by Lipopolysaccharide

  • QIU Guangzhi , 1 ,
  • ZHANG Mengwei 1 ,
  • GAO Chang 1 ,
  • WU Kaixin 1 ,
  • YU Lihuai 1 ,
  • DONG Li , 1, 2, *
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  • 1 College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
  • 2 Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 625014, China
* associate professor, E-mail:

Received date: 2024-03-21

  Online published: 2024-09-08

Abstract

The aim of this study was to investigate the regulatory effects of terpinen-4-ol (TER) on liver development, antioxidant capacity and immune function of weaned piglets under immune stress induced by LPS. Forty 28-day-old weaned piglets (weaned at 21 days of age) with similar body weight were selected and randomly divided into five groups with eight piglets per group. Piglets in the control group (CON group) and lipopolysaccharide group (LPS group) were fed a basal diet, and others in low, medium and high-dose terpinen-4-ol groups were fed the basal diet supplemented with 30 (PLT group), 60 (PMT group) and 90 mg/kg (PHT group) terpinen-4-ol, respectively. The pre-experimental period lasted for 3 days, and the experimental period lasted for 21 days. At the end of the experiment, the weaned piglets in LPS group and terpinen-4-ol groups were intraperitoneally injected with 100 μg/kg BW of LPS, while others in the control group were intraperitoneally injected with equivalent dose of 0.9% saline. The results showed as follows: 1) compared with CON group, the liver weight and liver index of LPS group were significantly decreased (P<0.05). Compared with LPS group, the liver weight of PHT group was significantly increased (P<0.05). 2) The cytoplasm of liver cells of CON group was intact, no obvious inflammation and necrosis were found; the liver tissue of LPS group was seriously damaged, including liver cell necrosis, cell swelling, cell membrane structure destruction and nuclear contraction. Compared with CON group, the area and particle size of liver cells of LPS group were significantly decreased (P<0.05). Compared with LPS group, the area and particle size of liver cells of PLT, PMT and PHT groups were significantly increased (P<0.05). 3) Compared with CON group, the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in liver of LPS group were significantly decreased (P<0.05). Compared with LPS group, the liver GSH-Px activity of PLT, PMT and PHT groups was significantly increased (P<0.05). 4) Compared with CON group, the liver interleukin-1β (IL-1β) content of LPS group was significantly increased (P<0.05). Compared with LPS group, the liver IL-1β content of PMT and PHT groups was significantly decreased (P<0.05), and the contents of interleukin-6 (IL-6) and interleukin-8 (IL-8) in liver of PHT group were significantly decreased (P<0.05). In conclusion, the LPS stimulation can lead to liver damage, liver antioxidant and immune function impairment. Dietary terpinen-4-ol can enhance antioxidant capacity and immune function and alleviate liver inflammatory damage of weaned piglets by increasing liver antioxidant oxidase activity, reducing pro-inflammatory factor content and increasing anti-inflammatory factor content.

Cite this article

QIU Guangzhi , ZHANG Mengwei , GAO Chang , WU Kaixin , YU Lihuai , DONG Li . Regulatory Effects of Terpinen-4-ol on Liver Development, Antioxidant Capacity and Immune Function of Weaned Piglets under Immune Stress Induced by Lipopolysaccharide[J]. Chinese Journal of Animal Nutrition, 2024 , 36(9) : 5608 -5616 . DOI: 10.12418/CJAN2024.478

在现代集约化和规模化养猪生产中,早期断奶技术已经得到普及[1]。仔猪断奶后环境和营养物质的改变易导致其产生免疫应激[2]。为了减少免疫应激给养猪业带来的损失,生产上往往采用在饲粮中添加抗生素来抑制断奶仔猪免疫应激。在饲料禁抗的背景下,寻求抗生素替代物缓解断奶仔猪免疫应激已经成为研究热点问题。4-萜品醇(terpinen-4-ol,TER)来源广泛,不仅存在于茶树油中,也存在于很多药用植物的精油中[3],可以有效抑制机体炎症反应[4-5]。课题组前期研究结果表明,在饲粮中添加茶树油(4-萜品醇含量约60%)可提高断奶仔猪生长性能,降低腹泻率,提高仔猪肠道屏障功能[6-7];并通过构建仔猪脂多糖(lipopolysaccharide,LPS)免疫损伤模型,发现4-萜品醇可有效提高断奶仔猪生长性能,有效改善仔猪肠道绒毛和微绒毛受损,缓解仔猪肠道炎症损伤[8]。肝脏是机体最大的代谢器官,是物质合成和分解的主要场所,由断奶引起的免疫应激可造成仔猪产生炎症反应,造成肝脏损伤,从而限制仔猪的生长发育,严重时甚至会造成仔猪死亡[9]。因此,本试验在前期研究基础上,解析不同添加量4-萜品醇对断奶仔猪肝脏发育、抗氧化能力和免疫功能的调节作用,以期为缓解断奶仔猪免疫应激提供新的营养干预方案和新的营养调控靶点。

1 材料与方法

1.1 伦理声明

本试验所有程序均按照扬州大学实验动物伦理委员会批准的方案进行,批准文号为202302040。

1.2 试验材料

本试验所用LPS为粉末状,来源于大肠杆菌O55∶B5;4-萜品醇为液体状,纯度95%。

1.3 试验设计

选取体重相近的28日龄仔猪40头(21日龄断奶),随机分为5组,每组8头仔猪,公母各占1/2。对照组(CON组)和脂多糖组(LPS组)饲喂基础饲粮,低、中和高剂量4-萜品醇组分别在基础饲粮中添加30(PLT组)、60(PMT组)和90 mg/kg(PHT组)的4-萜品醇。预试期3 d,正试期21 d,试验结束时,LPS组和各4-萜品醇组仔猪腹腔注射100 μg/kg BW的LPS,对照组仔猪腹腔注射等量的0.9%生理盐水。基础饲粮参照NRC(2012)标准配制,其组成及营养水平见表1
表1 基础饲粮组成及营养水平(风干基础)

Table 1 Composition and nutrient levels of the basal diet (air-dry basis) %

项目Items 含量Content
原料Ingredients
玉米Corn 10.00
鱼粉Fish meal 5.83
膨化玉米Puffed corn 27.67
大豆油Soybean oil 1.67
发酵豆粕Fermented soybean meal 8.00
大豆浓缩蛋白Soybean protein concentrate 2.50
全脂大豆Full fat soybean 6.50
乳清粉Whey powder 15.00
面粉Flour 10.00
稻壳粉Rice husk powder 0.33
葡萄糖Glucose 2.50
蔗糖Sucrose 5.00
载体稻壳粉Carrier rice husk powder 1.30
磷酸氢钙CaHPO4 0.15
L-赖氨酸L-Lys 0.43
蛋氨酸Met 0.30
苏氨酸Thr 0.29
色氨酸Trp 0.14
精氨酸Arg 0.39
缬氨酸Val 0.19
氯化胆碱Choline chloride 0.12
氯化钠NaCl 0.30
预混料Premix1) 1.39
合计Total 100.00
营养水平Nutrient levels2)
消化能DE/(MJ/kg) 14.40
粗蛋白质CP 18.40
钙Ca 0.74
总磷TP 0.52

1)预混料为每千克饲粮提供 The premix provided the following per kg of the diet:Fe 53 mg,Cu 5 mg,Mn 13 mg,Zn 40 mg,Co 0.06 mg,Se 0.23 mg,I 0.33 mg,VA 13 500 IU,VD3 2 750 IU,VE 6.25,VK3 1.25 mg,硫胺素 thiamine 0.5 mg,核黄素 riboflavin 3.75 mg,泛酸 pantothenic acid 6.25 mg,烟酸 nicotinic acid 8.75 mg,吡哆醇 adermin 0.5 mg,VB12 0.01 mg,生物素 biotin 0.013 mg,叶酸 folic acid 0.125 mg,植酸酶 phytase 500 mg,甜味剂 sweetener 200 mg,谷氨酸钠 sodium glutamate 1 000 mg,霉菌吸附剂 mold adsorbent 500 mg,抗氧化剂 antioxidant 200 mg。

2)消化能为计算值,其他营养水平为实测值。DE was a calculated value, while the other nutrient levels were measured values.

1.4 饲养管理

试验猪场为养殖试验基地,设备设施齐全,疫情防控管理严格。试验期结束(试验第21天)时对各组实施对应的刺激,6 h后屠宰取样[10]。仔猪自由采食和饮水,每日饲喂4次(07:00、11:00、15:00、19:00)。

1.5 测定指标及方法

1.5.1 饲粮营养成分

粗蛋白质(CP)含量采用凯氏定氮法(GB/T 6432—2018)测定,钙(Ca)和总磷(TP)含量分别参考GB/T 6436—2018和GB/T 6437—2018进行测定。消化能参照NRC(2012)计算,计算方式为每个原料的猪消化能乘以原料比例的总和。

1.5.2 肝脏发育指标

试验结束后,每个试验组随机选取6头仔猪称重,屠宰后进行肝脏的称重,计算每头仔猪的肝脏指数(肝脏重/活体重)。

1.5.3 肝脏组织结构

选取合适的1 cm厚的肝脏组织,用4%多聚甲醛固定,然后修样、洗涤、脱水,最后镜检、拍照。通过光学显微镜(Olympus CKX41,日本)观察组织细胞,于合适视野处拍照。通过Image-Pro Pius软件测量肝脏细胞面积和粒径。每个组织样切5张切片,每张切片计数3个不同视野下的30个细胞的面积和粒径,求平均值。

1.5.4 肝脏抗氧化指标

取0.1 g肝脏组织,加1 mL预冷的提取液制作10%匀浆,1 000×g离心取得上清液,存于-20 ℃冰箱保存备用。测定肝脏组织匀浆上清液中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量及总抗氧化能力(T-AOC),试剂盒均购自南京建成生物工程研究所,测定步骤按照试剂盒说明书进行。

1.5.5 肝脏免疫指标

取肝脏组织,按质量比1∶9加入生理盐水制成组织匀浆,1 000×g离心10 min取得上清液,存于-20 ℃冰箱保存备用。测定肝脏组织匀浆上清液中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和白细胞介素-10(IL-10)含量,采用酶联免疫吸附测定(ELISA)法,试剂盒购自北京索莱宝科技有限公司。

1.6 数据统计与处理

采用SPSS 18.0软件进行单因素方差分析,差异显著者用Duncan氏法进行多重比较,结果以平均值±标注差表示,P<0.05为差异显著,P>0.05为差异不显著。

2 结果

2.1 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏发育的影响

表2可知,与CON组相比,LPS组断奶仔猪活体重差异不显著(P>0.05),而肝脏重和肝脏指数显著降低(P<0.05)。与LPS组相比,PHT组断奶仔猪肝脏重显著提高(P<0.05)。
表2 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏发育的影响

Table 2 Effects of TER on liver development of weaned piglets under LPS-induced immune stress

项目
Items
组别Groups P
P-value
CON LPS PLT PMT PHT
活体重
Live body weight/kg
15.24±0.99b 15.53±0.94ab 15.93±0.43ab 16.27±0.49a 16.20±0.54a 0.008
肝脏重
Liver weight/g
599.94±53.50a 488.83±38.47b 534.11±56.92ab 566.00±83.90ab 583.85±78.58a 0.047
肝脏指数
Liver index/(g/kg)
39.37±2.58a 31.58±3.08b 33.60±4.27b 34.81±5.35ab 35.99±4.12ab 0.031

同行数据肩标不同小写字母表示差异显著(P<0.05),相同或无字母表示差异不显著(P>0.05)。下表同。

In the same row, values with different small letter superscripts mean significant difference (P<0.05), while with the same or no letter superscripts mean no significant difference (P>0.05). The same as below.

2.2 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏组织结构的影响

图1可知,CON组断奶仔猪肝脏细胞正常,细胞质完好,细胞核突出,核仁突出,未发现明显的坏死等现象,LPS组断奶仔猪肝脏组织出现严重损伤,包括肝脏细胞坏死、细胞肿胀、膜结构破坏以及核的缩小。各4-萜品醇组断奶仔猪的肝脏组织形态明显优于LPS组。
图1 免疫应激断奶仔猪肝脏组织切片

Fig.1 Liver tissue slices of weaned piglets under LPS-induced immune stress (40×)

表3可知,与CON组相比,LPS组断奶仔猪肝脏细胞面积和粒径均显著降低(P<0.05)。与LPS组相比,PLT、PMT和PHT组断奶仔猪肝脏细胞面积和粒径均显著提高(P<0.05)。
表3 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏细胞面积和粒径的影响

Table 3 Effects of TER on liver cell area and particle size of weaned piglets under LPS-induced immune stress

项目
Items
组别Groups P
P-value
CON LPS PLT PMT PHT
面积Area/μm2 163.28±2.65a 153.16±4.59b 163.19±3.87a 165.24±5.06a 166.08±4.24a <0.001
粒径Particle size/μm 6.48±1.58b 5.43±0.81c 7.90±1.21a 6.76±0.83b 7.11±1.00ab <0.001

2.3 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏抗氧化指标的影响

表4可知,与CON组相比,LPS组断奶仔猪肝脏CAT和GSH-Px活性显著降低(P<0.05)。与LPS组相比,PLT、PMT和PHT组断奶仔猪肝脏GSH-Px活性显著提高(P<0.05),肝脏CAT活性无显著差异(P>0.05)。各组之间断奶仔猪肝脏SOD活性、T-AOC和MDA含量无显著差异(P>0.05)。
表4 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏抗氧化指标的影响

Table 4 Effects of TER on liver antioxidant indices of weaned piglets under LPS-induced immune stress

项目
Items
组别Groups P
P-value
CON LPS PLT PMT PHT
过氧化氢酶
CAT/(U/mg prot)
63.20±3.67a 40.80±1.33b 49.29±2.55b 40.46±1.37b 37.14±7.41b <0.001
超氧化物歧化酶
SOD/(U/mg prot)
2.99±0.78 2.33±0.93 3.09±0.39 3.62±0.79 3.72±1.08 0.313
谷胱甘肽过氧化物酶
GSH-Px/(U/mg prot)
37.75±3.94b 19.19±2.36c 52.74±2.45ab 66.49±3.40a 44.90±7.51b 0.001
总抗氧化能力
T-AOC/(mmol/g prot)
0.36±0.12 0.27±0.05 0.23±0.02 0.23±0.10 0.27±0.06 0.055
丙二醛
MDA/(nmol/mg prot)
0.16±0.04 0.27±0.14 0.20±0.06 0.23±0.06 0.18±0.04 0.512

2.4 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏免疫指标的影响

表5可知,与CON组相比,LPS组断奶仔猪肝脏IL-1β含量显著升高(P<0.05),肝脏IL-6和IL-8含量无显著差异(P>0.05)。与LPS组相比,PMT和PHT组断奶仔猪肝脏IL-1β含量显著降低(P<0.05),PHT组断奶仔猪肝脏IL-6和IL-8含量显著降低(P<0.05)。各组之间断奶仔猪肝脏IL-4、TNF-α和IL-10含量无显著差异(P>0.05)。
表5 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏免疫指标的影响

Table 5 Effects of TER on liver immune indices of weaned piglets under LPS-induced immune stress

项目
Items
组别Groups P
P-value
CON LPS PLT PMT PHT
肿瘤坏死因子-α
TNF-α/(ng/g prot)
287.44
±88.53
451.44
±149.46
403.30
±193.73
422.50
±177.12
233.33
±146.03
0.089
白细胞介素-1β
IL-1β/(ng/g prot)
353.44
±214.95c
1 230.23
±521.79a
978.74
±496.52ab
677.08
±401.47bc
492.01
±456.17bc
0.011
白细胞介素-6
IL-6/(ng/g prot)
7 062.17
±1 809.60a
6 013.04
±1 533.24ab
4 868.44
±619.40bc
4 826.05
±1 527.64bc
3 875.72
±1 000.10c
0.004
白细胞介素-8
IL-8/(ng/g prot)
3 585.74
±1 422.48a
2 640.46
±574.88ab
1 864.01
±1 092.15bc
2 186.31
±757.53bc
1 180.63
±640.37c
0.003
白细胞介素-4
IL-4/(ng/g prot)
863.42
±120.41
755.69
±113.65
737.04
±227.35
938.89
±406.62
792.40
±112.65
0.531
白细胞介素-10
IL-10/(mg/g prot)
20.63
±1.93
19.05
±2.18
19.11
±0.65
19.51
±1.26
20.36
±1.00
0.633

3 讨论

3.1 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏发育的影响

内脏器官在动物身体中占有非常重要的地位,它们的正常发育对机体的生长发育具有重要作用。器官指数能够评价动物器官的生长情况,新陈代谢、机能等,以此来反映动物器官的发育和生理状态[11]。肝脏是动物体内十分重要的代谢器官,肝脏指数可以评价动物肝脏功能是否正常,当肝脏受损或产生病变时,肝脏指数会显著下降[12]。杨文等[13]研究发现,LPS诱导的免疫应激会导致断奶仔猪肝脏指数显著降低;Li等[14]研究发现,肝脏是铁吸收和代谢的重要场所,肝脏功能受损会影响机体对铁等矿物元素的吸收,进而影响机体生长发育。在本试验中,与CON组相比,LPS组断奶仔猪肝脏重和肝脏指数显著降低;而添加4-萜品醇可以提高断奶仔猪肝脏重和肝脏指数,可见LPS刺激可影响仔猪肝脏发育,而添加4-萜品醇可以缓解LPS诱导的仔猪肝脏发育受损。

3.2 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏组织结构的影响

免疫应激会引起断奶仔猪肝脏紊乱,肝窦充血,肝脏细胞肿胀、溶解、部分坏死及细胞核固缩,使肝脏处于炎症状态[15]。肝脏是体内最重要的代谢器官之一,在应激情况下,肠道中的有害物质会通过血液循环来到肝脏,造成肝脏细胞损伤,释放促炎因子,引起肝脏炎症[16]。秦坤等[17]研究表明,LPS处理会使仔猪肝脏出现明显损伤,肝脏细胞面积减少,肝脏细胞排列混乱,炎性细胞浸润。近年来,大量的研究表明断奶会导致仔猪产生免疫应激,并造成仔猪肝脏损伤[15]。本研究表明,CON组仔猪肝脏细胞正常,细胞质完好,细胞核突出,核仁突出,未发现明显的坏死等现象;LPS组仔猪肝脏组织出现严重损伤,包括肝脏细胞坏死、细胞肿胀、膜结构破坏以及核的缩小。各4-萜品醇组断奶仔猪肝脏组织形态明显优于LPS组。以上结果表明,LPS可诱导仔猪肝脏受损,而在饲粮中添加4-萜品醇能缓解免疫应激断奶仔猪的肝脏损伤。

3.3 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏抗氧化指标的影响

机体的免疫系统会产生活性氧(ROS)来杀死病原体,为了维持细胞完整性,ROS水平通常与抗氧化系统充分平衡,但是在内外环境的刺激下会使机体的抗氧化能力失调,致使机体内ROS水平与抗氧化系统不平衡,造成细胞、组织和器官的损伤[18-19]。断奶会引起仔猪生长迟缓和对疾病的易感性,导致断奶后应激综合征,引起仔猪体内氧化系统与抗氧化系统的不平衡,增加了仔猪肝脏应激和转氨酶,并启动了细胞凋亡[20]。细胞内酶促抗氧化剂(如SOD、CAT、GSH-Px)具有分解ROS的能力,对活性氧攻击具有有效的保护能力,SOD和CAT是体内最好的抗氧化剂,SOD可以催化超氧化物生成氧和过氧化氢,当机体受到刺激时,可迅速诱导生成SOD;CAT可以通过将过氧化氢分解成分子氧和水来中和过氧化氢[21]。MDA是脂质过氧化产物的标志,可以反映细胞内抗氧化功能的情况[22]。杨文[23]研究表明,LPS引发仔猪产生免疫应激,导致肝脏中CAT、GSH-Px活性和谷胱甘肽(GSH)含量显著降低,添加大黄草可明显缓解此现象。胡卫东等[24]研究表明,LPS会诱使肉鸡产生免疫应激,导致肝脏GSH-Px活性和T-AOC显著下降,CAT和T-SOD活性有下降趋势,添加赶黄草提取物可明显缓解此现象,提高抗氧化能力。Dong等[6]研究表明,饲粮中添加茶树油可以使断奶仔猪肝脏T-AOC显著增强,且效果优于抗生素;饲粮中添加50和100 mg/kg茶树油,断奶仔猪肝脏GSH-Px和SOD活性显著提高;饲粮中添加150 mg/kg茶树油,断奶仔猪肝脏GSH-Px活性显著提高,说明茶树油可以通过提高肝脏抗氧化能力,缓解断奶仔猪氧化损伤。本试验结果表明,LPS刺激可以导致仔猪肝脏CAT、GSH-Px活性显著降低,而添加4-萜品醇显著提高了肝脏GSH-Px活性。综上所述,LPS刺激可降低断奶仔猪肝脏抗氧化能力,4-萜品醇可以一定程度上提高仔猪肝脏的抗氧化能力,缓解LPS诱导免疫应激造成的断奶仔猪肝脏损伤。

3.4 4-萜品醇对LPS诱导免疫应激断奶仔猪肝脏免疫指标的影响

断奶仔猪容易发生疾病和感染,诱发仔猪产生免疫系统失调,并产生炎症反应[25]。炎症反应与细胞因子有关,促炎细胞因子(如IL-1β、IL-6和TNF-α)主要由活化的巨噬细胞产生,并参与炎症和神经性疼痛的发展;抗炎细胞因子(如IL-4,IL-10)是一系列控制促炎细胞因子反应的免疫调节分子,用于抵制炎症反应,其中IL-10是一种具有强效抗炎特性的细胞因子[26]。陈钦亮等[27]研究表明,注射LPS后仔猪肝脏组织炎性细胞因子TNF-αIL-6和IL-1β mRNA相对表达量显著升高,刺激肝脏分泌大量炎症因子。俞晓蓉等[28]研究发现,LPS处理会刺激仔猪肝脏IL-1β、IL-6和TNF-α含量显著增加,IL-10含量则显著下降,在仔猪饲粮中添加地衣芽孢杆菌可明显降低肝脏炎症损伤。本试验研究结果,与CON组相比,LPS刺激下断奶仔猪肝脏IL-1β含量显著上升,而添加4-萜品醇后肝脏IL-1β、IL-6、IL-8含量相比于LPS组下降。本研究结果提示,LPS刺激会诱导仔猪肝脏炎症反应,饲粮中添加4-萜品醇可以抑制促炎细胞因子表达,缓解仔猪肝脏炎症,进而提高仔猪肝脏免疫功能。

4 结论

① 饲粮中添加60 mg/kg 4-萜品醇能够减轻LPS诱导免疫应激断奶仔猪肝脏损伤。
② 饲粮中添加60 mg/kg 4-萜品醇能够提高LPS诱导免疫应激断奶仔猪肝脏抗氧化酶(尤其是GSH-Px)活性,进而提高肝脏抗氧化能力。
③ 饲粮中添加60 mg/kg 4-萜品醇能够降低LPS诱导免疫应激断奶仔猪肝脏炎症因子(尤其是IL-1β、IL-6、IL-8)含量,缓解肝脏炎症损伤。
[1]
李丽兰, 王玉. 浅谈保育猪的饲养管理措施[J]. 吉林畜牧兽医, 2023, 44(7):49-50.

LI L L, WANG Y. Discussion on breeding and management measures of conservation pigs[J]. Jilin Animal Husbandry and Veterinary Medicine, 2023, 44(7):49-50. (in Chinese)

[2]
魏媛媛, 张艳楠, 樊艺萌, 等. 仔猪断奶应激综合征与腹泻型肠易激综合征肝郁脾虚证对比研究[J]. 神经药理学报, 2022, 12(3):44-51.

WEI Y Y, ZHANG Y N, FAN Y M, et al. Comparative study on piglet weaning stress syndrome and diarrhea type irritable bowel syndrome with liver stagnation and spleen deficiency syndrome[J]. Acta Neuropharmacologica, 2022, 12(3):44-51. (in Chinese)

[3]
NASCIMENTO N R F, LEAL-CARDOSO J H, LESSA L M A, et al. Terpinen-4-ol:mechanisms of relaxation on rabbit duodenum[J]. Journal of Pharmacy and Pharmacology, 2005, 57(4):467-474.

[4]
NOGUEIRA M N M, AQUINO S G, ROSSA JUNIOR C, et al. Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1β,IL-6 and IL-10 on human macrophages[J]. Inflammation Research, 2014, 63(9):769-778.

[5]
NING J, XU L, ZHAO Q, et al. The protective effects of terpinen-4-ol on LPS-induced acute lung injury via activating PPAR-γ[J]. Inflammation, 2018, 41(6):2012-2017.

DOI PMID

[6]
DONG L, LIU J, ZHONG Z X, et al. Dietary tea tree oil supplementation improves the intestinal mucosal immunity of weanling piglets[J]. Animal Feed Science and Technology, 2019, 255:114209.

[7]
李洪民. 茶树油提取物活性成分4-萜品醇对仔猪肠道氧化损伤的调节作用[D]. 硕士学位论文. 扬州: 扬州大学, 2022.

LI H M. Regulatory effects of terpine-4-ol,an active component of tea tree oil extract,on intestinal oxidative damage in piglets[D]. Master’s Thesis. Yangzhou: Yangzhou University, 2022. (in Chinese)

[8]
刘军. 茶树油提取物4-萜品醇对仔猪肠道炎症损伤的调节作用[D]. 硕士学位论文. 扬州: 扬州大学, 2022.

LIU J. The regulatory effects of tea tree oil extract terpinen-4-ol on LPS-induced intestinal injury in weaned piglets[D]. Master’s Thesis. Yangzhou: Yangzhou University, 2022. (in Chinese)

[9]
侯晓晓, 马中华, 杨文, 等. 大黄素对免疫应激断奶仔猪肝脏抗氧化、抗炎性能的影响[J]. 中国畜牧杂志, 2023, 59(6):278-283.

HOU X X, MA Z H, YANG W, et al. Effect of Emodin on anti-oxidation and anti-inflammation in liver of immune-stressed weaned piglets[J]. Chinese Journal of Animal Science, 2023, 59(6):278-283. (in Chinese)

[10]
LIU Y L, HUANG J J, HOU Y Q, et al. Dietary arginine supplementation alleviates intestinal mucosal disruption induced by Escherichia coli lipopolysaccharide in weaned pigs[J]. British Journal of Nutrition, 2008, 100(3):552-560.

[11]
王小平, 张保军, 张展海, 等. 青贮杂交构树对育肥肉羊生长性能、屠宰性能及器官指数的影响[J]. 中国饲料, 2021(3):117-121.

WANG X P, ZHANG B J, ZHANG Z H, et al. Effects of broussonetia papyrifera silage on growth performance,slaughter performance and organ index in fattening sheep[J]. China Feed, 2021(3):117-121. (in Chinese)

[12]
李正田, 申智超, 刘帅歌, 等. 竹叶黄酮对济宁百日鸡早期增重及部分器官指数的影响[J]. 中国家禽, 2017, 39(8):52-54.

LI Z T, SHEN Z C, LIU S G, et al. Effects of bamboo leaf flavonoids on early weight gain and partial organ index of Jining Bairi hen[J]. China Poultry, 2017, 39(8):52-54. (in Chinese)

[13]
杨文, 马中华, 侯晓晓, 等. 大黄素对免疫应激仔猪器官指数、血清生化指标以及血清抗氧化能力的影响[J]. 饲料工业, 2022, 43(14):24-28.

YANG W, MA Z H, HOU X X, et al. Effects of emodin on organ index,serum biochemical indexes and serum antioxidant capacity in immune stressed piglets[J]. Feed Industry, 2022, 43(14):24-28. (in Chinese)

[14]
LI A M Y, YIN Q Q, DANG X W, et al. Effect of different Iron loads on serum and tissue biochemical parameters and liver hepcidin mRNA abundance of neonatal piglets[J]. Archives of Animal Nutrition:Archiv Fur Tierernahrung, 2011, 65(6):477-485.

[15]
车政权. 精氨酸对脂多糖刺激仔猪肝脏损伤的缓解作用及其机理[D]. 硕士学位论文. 武汉: 武汉工业学院, 2012.

CHE Z Q. Alleviative effect of arginine on liver injury of piglets after lipopolysaccharide challenge and its mechanism[D]. Master’s Thesis. Wuhan: Wuhan Polytechnic University, 2012. (in Chinese)

[16]
BRUNEAU A, HUNDERTMARK J, GUILLOT A, et al. Molecular and cellular mediators of the gut-liver axis in the progression of liver diseases[J]. Frontiers in Medicine, 2021, 8:725390.

[17]
秦坤, 王慧, 汪龙梅, 等. 羧甲基纤维素钠对脂多糖刺激仔猪肝脏损伤的保护作用[J]. 中国畜牧杂志, 2023, 59(9):310-314.

QIN K, WANG H, WANG L M, et al. Protective effect of sodium carboxymethyl cellulose on lipopolysaccharide-induced liver injury in piglets[J]. Chinese Journal of Animal Science, 2023, 59(9):310-314. (in Chinese)

[18]
SADASIVAM N, KIM Y J, RADHAKRISHNAN K, et al. Oxidative stress,genomic integrity,and liver diseases[J]. Molecules, 2022, 27(10):3159.

[19]
AGITA A, ALSAGAFF M T. Inflammation,immunity,and hypertension[J]. Acta Medica Indonesiana, 2017, 49(2):158-165.

[20]
LUO Z, ZHU W, GUO Q, et al. Weaning induced hepatic oxidative stress,apoptosis,and aminotransferases through MAPK signaling pathways in piglets[J]. Oxidative Medicine and Cellular Longevity, 2016, 2016:4768541.

[21]
HE L, HE T, FARRAR S, et al. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species[J]. Cellular Physiology and Biochemistry, 2017, 44(2):532-553.

DOI PMID

[22]
JELIC M D, MANDIC A D, MARICIC S M, et al. Oxidative stress and its role in cancer[J]. Journal of Cancer Research and Therapeutics, 2021, 17(1):22-28.

DOI PMID

[23]
杨文. 大黄素对免疫应激仔猪肝脏损伤的作用及机理研究[D]. 硕士学位论文. 海口: 海南大学, 2023.

YANG W. Study on the effect and mechanism of emodin on liver damage in immune stressed piglets[D]. Master’s Thesis. Haikou: Hainan University, 2023. (in Chinese)

[24]
胡卫东, 杜林, 张莉, 等. 日粮中添加赶黄草提取物对免疫应激肉仔鸡炎症反应的影响及其肝脏保护作用[J]. 中国兽医学报, 2024, 44(1):192-198, 216.

HU W D, DU L, ZHANG L, et al. Effect of dietary supplementation of Penthorum chinense Pursh extract on in-flammatory response and hepatoprotective effect in immune-stressed broilers[J]. Chinese Journal of Veterinary Science, 2024, 44(1):192-198, 216. (in Chinese)

[25]
GUAN X N, SANTOS R R, KETTUNEN H, et al. Effect of resin acid and zinc oxide on immune status of weaned piglets challenged with E.coli lipopolysaccharide[J]. Frontiers in Veterinary Science, 2021, 8:761742.

[26]
ZHANG J M, AN J. Cytokines,inflammation,and pain[J]. International Anesthesiology Clinics, 2007, 45(2):27-37.

[27]
陈钦亮, 汪洋, 李先根, 等. 脂多糖对仔猪肝脏损伤和程序性坏死信号通路关键基因表达的影响[J]. 中国畜牧杂志, 2022, 58(9):271-274, 278.

CHEN Q L, WANG Y, LI X G, et al. Effect of lipopolysaccharide on the expression of key genes in liver injury and programmed necrosis signaling pathway in piglets[J]. Chinese Journal of Animal Science, 2022, 58(9):271-274, 278. (in Chinese)

[28]
俞晓蓉, 代兵, 刘金松, 等. 地衣芽孢杆菌对脂多糖诱导的仔猪肝脏炎症及抗氧化功能的影响[J]. 微生物学报, 2023, 63(3):1283-1294.

YU X R, DAI B, LIU J S, et al. Effects of Bacillus licheniformis on lipopolysaccharide-induced liver inflammation and antioxidant function in weaned piglets[J]. Acta Microbiologica Sinica, 2023, 63(3):1283-1294. (in Chinese)

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