桦木酸对环磷酰胺致小鼠肝脏损伤的保护作用

doi:10.7506/spkx1002-6630-20191028-312

食品科学 ›› 2020, Vol. 41 ›› Issue (21): 147-153.doi: 10.7506/spkx1002-6630-20191028-312

桦木酸对环磷酰胺致小鼠肝脏损伤的保护作用

马朝阳，朱利娟，罗晨曦，朱子寒，孔丽，林星，高鑫禹，马玉容，欧朝萍，易金娥

（1.湖南农业大学动物医学院，湖南长沙 410128；2.畜禽保健湖南省工程研究中心，湖南长沙 410128；3.湖南畜禽安全生产协同创新中心，湖南长沙 410128）

发布日期:2020-11-23
基金资助:
湖南省教育厅重点项目（17A098）；湖南省研究生创新基金项目（CX2018B411）；湖南农业大学“双一流”学科建设项目（SYL2019049）；湖南省发展与改革委员会创新研发项目（37）

Protective Effect of Betulinic Acid on Cyclophosphamide-Induced Liver Injury in Mice

MA Chaoyang, ZHU Lijuan, LUO Chenxi, ZHU Zihan, KONG Li, LIN Xing, GAO Xinyu, MA Yurong, OU Zhaoping, YI Jin’e

1. School of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China; 2. Hunan Engineering Research Center of Livestock and Poultry Health Care, Changsha 410128, China; 3. Hunan Co-innovation Center of Animal Production Safety, Changsha 410128, China

Published:2020-11-23

摘要/Abstract

摘要： 为了探究桦木酸（betulinic acid，BA）对环磷酰胺（cyclophosphamide，CYP）导致的肝脏损伤的影响。将50 只昆明小鼠随机分为5 个组，即空白组、CYP组以及BA低、中、高剂量组。空白组和CYP组用1%（质量分数，下同）的可溶性淀粉灌胃，而其余各组按0.25、0.50、1.00 mg/kg mb BA剂量混悬在1%可溶性淀粉糊中灌胃，连续灌胃14 d后，除空白组腹腔注射生理盐水外，其余各组连续2 d腹腔注射CYP（50 mg/kg mb）诱导肝损伤模型。检测血清中谷丙转氨酶（alanine aminotransferase，ALT）和谷草转氨酶（aspartate aminotransferase，AST）活力；检测肝脏超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）、过氧化氢酶（catalase，CAT）活力，以及还原型谷胱甘肽（glutathione，GSH）和丙二醛（malondialdehyde，MDA）含量；荧光定量聚合酶链式反应检测肝脏促炎因子白细胞介素（interleukin，IL）-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、IL-1β和抗炎因子IL-10 mRNA的相对表达量。结果表明：1）与CYP组相比，BA预处理使小鼠体质量增加，其中0.50 mg/kg mb BA组显著增加（P＜0.05），同时使肝脏指数降低，其中0.50 mg/kg mb和1.00 mg/kg mb BA组显著降低（P＜0.05）；2）BA呈剂量依赖性降低AST的活力，其中1.00 mg/kg mb BA组显著降低（P＜0.05），0.50 mg/kg mb BA组显著降低ALT活力（P＜0.05）；3）BA预处理缓解由CYP导致的空泡样变性；4）BA预处理降低肝脏SOD活力，其中0.25 mg/kg mb BA组显著降低（P＜0.05），BA对肝脏GSH-Px、CAT、GSH和MDA水平无明显影响（P＞0.05）；5）0.25 mg/kg mb和1.00 mg/kg mb BA缓解CYP引起的IL-1β mRNA表达升高（P＜0.05，P＜0.01），BA极显著增加肝脏中IL-6（P＜0.01）和IL-10 mRNA的表达（P＜0.01），0.25 mg/kg mb BA增加肝脏TNF-α mRNA的表达，但0.50 mg/kg mb和1.00 mg/kg mb BA降低肝脏TNF-α mRNA的表达（P＜0.01）。结论：BA能抑制CYP引起的血清酶活力改变，改善小鼠肝脏的脂质过氧化，抑制促炎因子分泌，促进抗炎因子的分泌，对CYP诱导的肝脏损伤具有预防性保护作用。

关键词: 桦木酸；环磷酰胺；氧化应激；抗炎；肝脏损伤

Abstract: The objective of this study was to evaluate the preventive effect of betulinic acid (BA) on cyclophosphamide (CYP)-induced liver injury in mice. Fifty male healthy Kunming mice were randomly divided into 5 groups including control, CYP, and low-, medium- and high-dose BA groups. The mice from the control and CYP groups were administered orally with 1% starch solution, and those from the other groups with BA at doses of 0.25, 0.50 and 1.00 mg/kg mb for 14 days. Afterwards liver injury was induced by intraperitoneal injection of CYP at a dose of 50 mg/kg mb for 2 days for all groups except the control group, which was injected with physiological saline solution. The activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in the liver, and the mRNA expression of pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and (IL-1β) and anti-inflammatory cytokine (IL-10) in liver were determined. The results showed as follows: 1) Pretreatment with BA increased the body mass of mice significantly at a dose of 0.50 mg/kg mb (P < 0.05), reduced the liver index significantly at 0.50 and 1.00 mg/kg mb (P < 0.05) when compared with the CYP group. 2) BA pretreatment decreased the activity of AST in a dose-dependent manner, and the effect showed a significant difference (P < 0.05) at 0.50 and 1.00 mg/kg mb. 3) Pretreatment with BA decreased hepatic vacuole degeneration caused by CYP. 4) BA reduced the activity of hepatic SOD (P < 0.05) significantly at 0.25 mg/kg mb, but had no effects on the levels of GSH-Px, CAT, GSH and MDA (P > 0.05) in the liver. 5) BA pretreatment at 0.25 and 1.00 mg/kg mb attenuated the CYP-induced increase in the mRNA expression of IL-1β (P < 0.05, P < 0.01), and significantly increased the mRNA expression of IL-6 and IL-10 (P < 0.01). At the same time, BA decreased the mRNA expression of TNF-α in the liver at 0.50 and 1.00 mg/kg mb (P < 0.01), but increased it at 0.25 mg/kg mb. Therefore, BA has a preventive effect against CYP-induced hepatic damage in mice via inhibiting the activity of antioxidant enzymes in the serum, decreasing lipid peroxidation in the liver, inhibiting the secretion of pro-inflammatory cytokines, and promoting the secretion of anti-inflammatory cytokines.

Key words: betulinic acid; cyclophosphamide; oxidative stress; anti-inflammatory; liver injury

中图分类号:

马朝阳，朱利娟，罗晨曦，朱子寒，孔丽，林星，高鑫禹，马玉容，欧朝萍，易金娥. 桦木酸对环磷酰胺致小鼠肝脏损伤的保护作用[J]. 食品科学, 2020, 41(21): 147-153.

MA Chaoyang, ZHU Lijuan, LUO Chenxi, ZHU Zihan, KONG Li, LIN Xing, GAO Xinyu, MA Yurong, OU Zhaoping, YI Jin’e. Protective Effect of Betulinic Acid on Cyclophosphamide-Induced Liver Injury in Mice[J]. FOOD SCIENCE, 2020, 41(21): 147-153.

桦木酸对环磷酰胺致小鼠肝脏损伤的保护作用

Protective Effect of Betulinic Acid on Cyclophosphamide-Induced Liver Injury in Mice

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