18β-甘草次酸可缓解D-半乳糖诱导断奶仔猪氧化应激肺损伤

doi:10.11843/j.issn.0366-6964.2026.01.026

摘要/Abstract

摘要：

旨在研究18β-甘草次酸（18β-glycyrrhetinic acid，18β-GA）对D-半乳糖（D-galactose，D-gal）诱导断奶仔猪氧化应激肺损伤的影响。将24头体重相近的28日龄断奶仔猪随机分3组，每组8个重复，每个重复1头猪，试验分组为：对照组（CK）饲喂基础日粮，模型组（D-gal）饲喂基础日粮添加10 g·kg^-1 D-gal，试验组（GA+gal）饲喂基础日粮添加10 g·kg^-1 D-gal和100 mg·kg^-1 18β-GA。预试期7 d，正试期28 d。结果表明：与CK组相比，D-gal组断奶仔猪肺组织丙二醛（malondialdehyde，MDA）含量、8-羟基脱氧鸟苷（8-hydroxy-2-deoxyguanosine，8-OHdG）含量、过氧化氢酶（catalase，CAT）活性有上升趋势（0.05≤P<0.10），超氧化物歧化酶（superoxide dismutase，SOD）活性显著上升（P<0.05）；Nrf2、CAT、SOD1基因表达量显著上升（P<0.05）；炎症因子白细胞介素-8（interleukin-8，IL-8）、转化生长因子-β（transforming growth factor-β，TGF-β）含量显著升高（P<0.05），肺泡平均内衬间隔（mean linear intercept，MLI）、肺组织细胞凋亡率显著升高（P<0.05）；与D-gal组相比，GA+gal组肺组织中CAT和SOD活性、MDA和8-OHdG含量及抗氧化相关基因Nrf2、CAT、SOD1表达量显著降低（P<0.05），炎症因子IL-8、白细胞介素-18（interleukin-18，IL-18）、TGF-β含量显著降低（P<0.05），细胞凋亡率显著降低（P<0.05）。转录组学分析表明氧化应激对仔猪肺脏细胞周期、PI3K/AKT信号通路、P53信号通路有影响，18β-GA可以通过调节PI3K/AKT信号通路、视黄醇代谢等通路缓解肺损伤。利用荧光定量PCR和Western blot技术进一步验证发现，仔猪氧化应激后通路关键基因PI3K、AKT、TP53和蛋白P53表达水平升高（P<0.05）；添加18β-GA后能使通路基因PI3K、TP53表达量降低（P<0.05），AKT基因表达水平、P53蛋白表达水平有降低的趋势（0.05≤P<0.1）。综上所述，添加18β-GA可以缓解D-gal诱导的断奶仔猪肺脂质过氧化、DNA氧化损伤，炎症因子增多、细胞凋亡发生等损伤，其机制可能是通过调节P53信号通路缓解肺损伤。

关键词: 氧化应激, 肺损伤, 甘草次酸, 断奶仔猪, 转录组

Abstract:

The aim of this experiment is to investigate the effect of 18β-glycyrrhetinic acid （18β-GA） on oxidative stress induced lung injury in weaned piglets induced by D-galactose （D-gal）.In total， 24 weaned piglets of similar body weight at 28 days old were randomly divided into 3 groups， with 8 replicates in each group and 1 piglet in each replicate. The experimental groups were as follows： the control group （CK） was fed with basal diet， the model group （D-gal） was fed with basal diet supplemented with 10 g·kg^-1 D-gal， and the experimental group （GA+gal） was fed with basal diet supplemented with 10 g.kg^-1 D-gal and 100 mg·kg^-1 18 β-GA. The pre trial period is 7 days， and the main trial period is 28 days. The results showed that compared with the CK group， the D-gal group showed an increase trend in malondialdehyde （MDA） content， 8-hydroxy-2-deoxyguanosine （8-OHdG） content， and catalase （CAT） activity in the lung tissue of weaned piglets （0.05≤P<0.10）， and a significant increase in superoxide dismutase （SOD） activity （P<0.05）； The expression levels of Nrf2， CAT， and SOD1 genes significantly increased （P<0.05）； The levels of inflammatory factors interleukin-8 （IL-8） and transforming growth factor-β （TGF-β） increased significantly （P<0.05）， and the mean linear intercept （MLI） and apoptosis rate of lung tissue cells increased significantly （P<0.05）； Compared with the D-gal group， the GA+gal group showed a significant decrease in the activities of CAT and SOD， content of MDA and 8-OHdG， as well as the expression levels of antioxidant related genes Nrf2， CAT， and SOD1 in the lungs （P<0.05）. The levels of inflammatory factors IL-8， interleukin-18 （IL-18）， and TGF-β were also reduced significantly （P<0.05）， and the apoptosis rate was also reduced significantly （P<0.05）. Transcriptomic analysis showed that oxidative stress has an impact on the cell cycle， PI3K/AKT signaling pathway， and P53 signaling pathway in piglet lung cells. 18β-GA can alleviate lung injury by regulating pathways such as PI3K/AKT signaling pathway and retinol metabolism. Further verification using fluorescence quantitative PCR and Western blot techniques revealed that the expression levels of key genes PI3K， AKT， TP53， as well as proteins P53 in the oxidative stress pathway of piglets increased significantly （P<0.05）. After adding 18β-GA， the expression levels of pathway genes PI3K and TP53 decreased significantly （P<0.05）， while the expression levels of gene AKT and protein P53 showed a downward trend （0.05≤P<0.1）.In summary， the addition of 18β-GA can alleviate D-gal induced lipid peroxidation， DNA oxidative damage， increased inflammatory factors， and cell apoptosis in weaned piglet lungs. The underlying mechanism might involve the alleviation of lung injury through the modulation of the P53 signaling pathways.

Key words: oxidative stress, lung injury, glycyrrhetinic acid, weaned piglets, transcriptome

中图分类号:

S828.5

王伏羲, 马翠, 黄康, 李蕊彤, 赵青余, 张军民, 闫益波, 司玮. 18β-甘草次酸可缓解D-半乳糖诱导断奶仔猪氧化应激肺损伤[J]. 畜牧兽医学报, 2026, 57(1): 305-316.

WANG Fuxi, MA Cui, HUANG Kang, LI Ruitong, ZHAO Qingyu, ZHANG Junmin, YAN Yibo, SI Wei. 18β-glycyrrhetinic Acid can Alleviate Oxidative Stress Induced Lung Injury in Weaned Piglets Induced by D-galactose[J]. Acta Veterinaria et Zootechnica Sinica, 2026, 57(1): 305-316.

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项目 Item	含量 Content
原料组成 Raw material composition
玉米 Corn	42.83
膨化玉米 Puffed corn	12.00
46%豆粕46% Soybean meal	11.00
膨化大豆 Extruded full-fat soybean	8.80
大豆浓缩蛋白 Soybean protein concentrate	4.50
乳清粉 Whey powder	10.00
鱼粉 Fish meal	3.10
豆油 Soybean oil	0.60
石粉 Limestone	0.65
磷酸氢钙 Calcium monophosphate	1.20
氯化钠 Sodium chloride	0.30
葡萄糖 Glucose	3.00
98.5%赖氨酸98.5% Lysine	0.54
98.5%蛋氨酸98.5% Methionine	0.22
苏氨酸 Threonine	0.21
色氨酸 Tryptophan	0.05
预混料^① Premix	1.00
合计 Total	100.00
营养成分^② Nutrient level
净能/（MJ·kg^-¹ ） Net energy	10.58
粗蛋白质 Crude protein	18.92
钙 Calcium	1.21
赖氨酸 Lysine	1.41
蛋氨酸 Methionine	0.54
苏氨酸 Threonine	0.85
色氨酸 Tryptophan	0.25
蛋氨酸+半胱氨酸 Methionine+Cysteine	0.85

项目 Item	CK组 CK group	D-gal组 D-gal group	GA+gal组 GA+gal group	P值 P-value
CAT/（μmol·（min·mg）^-1）	588.08±60.28^ab	747.22±63.91^a	428.93±40.06^b	0.010
SOD/（U·mg^-1）	0.15±0.01^b	0.21±0.02^a	0.13±0.01^b	0.015
MDA/（nmol·g^-1）	1.45±0.08^ab	1.66±0.14^a	1.04±0.16^b	0.004
8-OHdG/（ng·g^-1）	55.32±5.98^ab	84.17±12.88^a	34.90±7.54^b	0.014

项目 Item	CK组 CK group	D-gal组 D-gal group	GA+gal组 GA+gal group	P值 P-value
PI3K	1.13±0.23^b	2.32±0.31^a	1.28±0.17^b	0.009
AKT	1.01±0.18^b	2.34±0.49^a	1.45±0.16^ab	0.031
TP53	0.78±0.09^b	2.46±0.40^a	1.10±0.11^b	<0.001