花姜酮对小鼠急性肝损伤的保护作用机制研究  

Protective effect and mechanism of zerumbone on acute liver injury in mice

作　　者：牛精铃 王子仪 张明炎 莫现安 马凤群 杨庆和 刘玲[1] 王梅林 NIU Jing-ling;WANG Zi-yi;ZHANG Ming-yan;MO Xian-an;MA Feng-qun;YANG Qing-he;LIU Ling;WANG Mei-lin(School of Basic Medical Sciences,HenanUniversity of Science and Technology,Luoyang 471023,Henan Province,China)

机构地区：[1]河南科技大学基础医学院,河南洛阳471023

出　　处：《中国临床药理学杂志》2021年第9期1074-1077,1082,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(31500631);河南科技大学大学生科研训练计划(SRTP)基金资助项目(2019331,2019334)。

摘　　要：目的研究花姜酮(ZER)对四氯化碳(CCl4)致化学性和对乙酰氨基酚(APAP)致药物性小鼠急性肝损伤的保护作用机制。方法用CCl4致小鼠化学性急性肝损伤组和用APAP致小鼠药物性急性肝损伤组。按照体重将2种模型各分为5组:正常组,模型组,阳性对照组(联苯双酯350μmol·kg^(-1))和低、高2个剂量实验组(花姜酮2,8μmol·kg^(-1)),每组10只。酶法测定血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)活力,酶法测定肝匀浆中超氧化物歧化酶(SOD)和丙二醛(MDA)的水平,蛋白质印迹法检测肝组织中转化生长因子β(TGF-β)和Smad蛋白3(Smad3)表达水平。结果 (1)化学性急性肝损伤小鼠模型:正常组、模型组、低剂量实验组、高剂量实验组和阳性对照组小鼠血清GOT酶活力分别为(62.30±5.99),(282.47±18.07),(169.94±39.88),(96.71±25.91)和(128.43±14.56)U·L^(-1);这5组的血清GPT酶活力分别为(40.70±2.96),(272.38±12.20),(167.79±20.56),(87.46±25.08)和(126.74±11.45)U·L^(-1);这5组的肝组织中SOD酶活力分别为(89.27±3.47),(45.31±3.37),(59.89±2.92),(76.46±5.83)和(73.31±2.83)U·mg^(-1);这5组的肝组织中MDA含量分别为(4.77±0.31),(9.91±0.73),(8.21±0.53),(4.95±0.40)和(5.56±0.41)nmol·mg^(-1) 。正常组、模型组和低、高2个剂量实验组TGF-β蛋白表达量分别为0.76±0.02,1.00±0.09,0.74±0.08和0.46±0.10;这4组的Smad3蛋白表达量分别为0.64±0.02,1.00±0.12,0.89±0.07和0.63±0.08。上述指标:模型组与正常组相比,差异均有统计学意义(P<0.05,P<0.01);低、高2个剂量实验组与模型组相比,差异均有统计学意义(P<0.05,P<0.01)。(2)药物性急性肝损伤小鼠模型:与化学性急性肝损伤小鼠实验中上述各指标的变化趋势一致。结论花姜酮对小鼠急性肝损伤具有保护作用,其机制可能与抗氧化应激和自由基清除有关;花姜酮对急性肝损伤的保护作用与其下调TGF-β和Smad3蛋白表达水平有关。Objective To explore the protective effect and mechanism of zerumbone(ZER) on the different types of acute liver injury induced by carbon tetrachloride(CCl4) and acetaminophen(APAP). Methods Acute liver injury mice induced by CCl4 and by APAP,respectively. The two models were divided into 5 groups according to weight: normal group, model group, positive control group(BIF, 350 μmol·kg ^(-1)), and low and high dose(ZER 2,8 μmol·kg ^(-1)) experimental groups, 10 mice in each group. The activities of glutamic-pyruvic transaminase ( GPT) and glutamic-oxaloacetic transaminase( GOT) in serum and the superoxide dismutase( SOD) activities and malondialdehyde( MDA) levels in liver homogenates were determined using commercialized kits. The protein expression of transforming growth factor-β( TGF-β) and Smad3 protein in liver tissue were analyzed by Western blot. Results( 1) A mice model of chemical acute liver injury: the activities of serum GOT in normal group,model group,low dose experimental group, high dose experimental group and positive control group were( 62. 30 ± 5. 99),( 282. 47 ± 18. 07),( 169. 94 ± 39. 88),( 96. 71 ± 25. 91) and( 128. 43 ± 14. 56) U·L^(-1);the activities of serum GPT in the 5 groups were( 40. 70 ± 2. 96),( 272. 38 ± 12. 20),( 167. 79 ± 20. 56),( 87. 46 ± 25. 08) and( 126. 74 ± 11. 45) U·L^(-1);the activities of enzyme SOD in the 5 groups were( 89. 27 ± 3. 47),( 45. 31 ± 3. 37),( 59. 89 ± 2. 92),( 76. 46 ± 5. 83) and( 3. 31 ± 2. 83) U · mg^(-1);the content of MDA in the 5 groups were( 4. 77 ± 0. 31),( 9. 91 ± 0. 73),( 8. 21 ± 0. 53),( 4. 95 ± 0. 40) and( 5. 56 ± 0. 41) nmol·mg^(-1). The protein expression of TGF-β in normal group,model group,low dose experimental group,high dose experimental group were0. 76 ± 0. 02,1. 00 ± 0. 09,0. 74 ± 0. 08 and 0. 46 ± 0. 10;the protein expression of Smad3 in the four groups were0. 64 ± 0. 02,1. 00 ± 0. 12,0. 89 ± 0. 07 and 0. 63 ± 0. 08. Comparison between model group and normal group,the differences of the factors were sig

关 键 词：花姜酮 四氯化碳 对乙酰氨基酚 急性肝损伤 转化生长因子Β Smad蛋白3 

分 类 号：R28[医药卫生—中药学]