摘要
目的研究枸杞多糖(lyciumbarbarum polysaccharides,LBP)对D-氨基半乳糖(D-Galactosamine,D-Gal)联合脂多糖(lipopolysaccharide,LPS)诱导的小鼠急性肝损伤的拮抗作用,并初步探究其机制。方法将48只健康SPF级雄性C57BL/6小鼠随机分为6组,分别为对照组、肝损伤模型(400 mg/kg D-Gal+10μg/kg LPS)组、LBP(400 mg/kg)组及低剂量(100 mg/kg)、中剂量(200 mg/kg)、高剂量(400 mg/kg)LBP干预组,每组8只。采用灌胃方式给予LBP(给药容积为10 ml/kg),每日1次,对照组及肝损伤模型组小鼠灌胃给予等体积无菌生理盐水,持续28 d;末次给药2 h后,LBP干预组及肝损伤模型组小鼠腹腔注射给予D-Gal、LPS,以建立小鼠急性肝损伤模型,给予对照组及LBP组小鼠等体积无菌生理盐水。通过比较各组小鼠的肝重、肝脏系数和血清中丙氨酸氨基转移酶(alanine transaminase,ALT)、天冬氨酸氨基转移酶(aspartate transaminase,AST)和乳酸脱氢酶(lactate dehydrogenase,LDH)水平以及肝组织病理学,评价LBP对D-Gal/LPS诱导的肝损伤的拮抗作用;并检测肝组织中丙二醛(malondialdehyde,MDA)、还原型谷胱甘肽(reduced glutathione,GSH)含量及超氧化物歧化酶(superoxide dismutase,SOD)活力。结果与对照组相比,肝损伤模型组小鼠肝重、肝脏系数、血清肝损伤标志酶ALT、AST和LDH水平均升高,差异有统计学意义(P<0.05);LBP干预后可显著抑制D-Gal和LPS诱导的肝重、肝脏系数的增加和ALT、AST、LDH活力升高(P<0.05);而且随着LBP干预剂量的增加效果越明显。肝损伤模型组小鼠肝小叶可见大面积出血、坏死和炎细胞浸润,LBP预处理能显著拮抗上述病变,而且随着LBP干预剂量的增加,改善效果越明显。与对照组相比,肝损伤模型组小鼠肝组织MDA水平升高,GSH、SOD水平均降低,差异有统计学意义(P<0.05);LBP干预显著抑制了D-Gal和LPS诱导的MDA水平升高和GSH、SOD水平的降低(P<0.05),且随着LBP干预剂量的升高,小鼠肝组织MDA水平均呈下降趋势,而GSH、SOD水平均呈升高趋势。尽管LBP预处理显著拮抗了D-Gal和LPS诱导的肝损伤,但与对照组各指标相比,仅400 mg/kg的LBP干预后ALT活力与对照组相比差异无统计学意义(P>0.05)。结论LBP对D-Gal+LPS诱导的急性肝损伤具有一定的拮抗作用,其机制可能与减轻肝脏氧化应激有关。
Objective To understand the antagonistic effect of lyciumbarbarum polysaccharides(LBP)on acute liver injury induced by D-Galactosamine(D-Gal)combined with lipopolysaccharide(LPS)in mice,and to explore the underlying mechanisms.Methods Totally 48 male C57BL/6 mice were randomly divided into six groups:control group,liver injury model group(400 mg/kg D-Gal combined with 10μg/kg LPS),LBP group,LBP low,moderate,and high dose intervention group(LBP 100,200,400 mg/kg),with 8 mice in each group.LBP was administered by gavage at 10 mg/kg,once a day for 28 days.The mice in control and liver injury model groups were given an equal volume of sterile saline.Two hours after the last administration,the mice in LBP intervention groups and liver injury model group were intraperitoneally injected with D-Gal plus LPS.The mice in control group and LBP group were given equal volumes of saline.The liver weight,liver coefficient,the levels of alanine transaminase(ALT),aspartate transaminase(AST),and lactate dehydrogenase(LDH)in serum and liver tissue pathology of each group were detected,and the antagonistic effects of LBP were evaluated based on these.The levels of malondialdehyde(MDA),glutathione(GSH)and superoxide dismutase(SOD)in mice were determined.Results Compared with the control group,the liver weight,liver coefficient,the serum levels of ALT,AST and LDH significantly increased(P<0.05).LBP intervention could significantly inhibit the increase in liver weight,liver coefficient,and ALT,AST,and LDH activities induced by D-Gal and LPS challenge(P<0.05),and the effects became more pronounced with the increase of LBP dose.The bleeding,necrosis,and infiltration of inflammatory cells could be observed in the liver lobules of mice in the liver injury model group.LBP pretreatment could significantly antagonize these lesions,and the improvement effect became more significant with the increase of LBP dose.Compared with the control group,MDA level in liver tissue of liver injury model group increased,GSH and SOD levels decreased,with significant differences(P<0.05).LBP intervention significantly inhibited the increase of MDA level and the decrease of GSH and SOD levels induced by D-Gal and LPS(P<0.05).Moreover,with the increase of LBP intervention dose,MDA levels in liver tissue of mice showed a decreasing trend,while the GSH and SOD levels showed an increasing trend.Although LBP pretreatment significantly antagonized the liver injury induced by D-Gal and LPS,there was no statistical difference in ALT activity with 400 mg/kg LBP pretreatment compared to the control group(P>0.05).Conclusion LBP has obvious protective effect against the acute liver injury induced by D-Gal plus LPS,and the underlying mechanism may be related to reducing oxidative stress in liver.
作者
于婷
张瑞涵
胡新洁
李宗耀
胡延真
王子铭
张翠丽
YU Ting;ZHANG Rui-han;HU Xin-jie;LI Zong-yao;HU Yan-zhen;WANG Zi-ming;ZHANG Cui-li(Institute of Toxicology,School of Public Health,Cheeloo College of Medicine,Shandong University,Jinan,Shandong 250012,China)
出处
《环境与健康杂志》
2025年第3期189-194,F0003,共7页
Journal of Environment and Health
基金
山东省自然科学基金(ZR2022MH014)
2021年国家级大学生创新创业训练计划(202110422226)。
关键词
急性肝损伤
D-氨基半乳糖
脂多糖
枸杞多糖
氧化应激
Acute liver injury
D-galactosamine
Lipopolysaccharide
Lyciumbarbarum polysaccharides
Oxidative stress
作者简介
于婷(2000-),女,本科在读,从事肝脏毒理学研究;通信作者:张翠丽,E-mail:zcuilisdu@sdu.edu.cn。
