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基于蛋白组学探讨羟基红花黄色素A对急性肝损伤的作用机制

The mechanism of hydroxysafflor yellow A on acute liver injury based on proteomics
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摘要 目的基于蛋白组学的方法探讨羟基红花黄色素A(Hydroxysafflor yellow A,HSYA)对急性肝损伤(acute liver injury,ALI)的作用机制。方法将雄性Wistar大鼠随机分为正常对照组、四氯化碳(CCl 4)模型组和羟基红花黄色素A低、中、高剂量组[10、20、40 mg/(kg·d)],每组10只。正常对照组、模型组腹腔注射生理盐水,羟基红花黄色素A组按不同浓度腹腔注射给药,持续8天。第8天给药后的1小时,其余组大鼠一次性腹腔注射50%CCl 4花生油溶液(0.1 mL/100 g)建立ALI模型,正常对照组注射等体积的花生油。24小时后解剖计算大鼠肝脏系数;检测大鼠血清肝功能指标[丙氨酸转氨酶(alanine transaminase,ALT)、天冬氨酸转氨酶(aspartate transaminase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)]含量、氧化指标[超氧化物歧化酶(superoxide dismutase,SOD)活性、丙二醛(malondialdehyde,MDA)]以及炎症因子[肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)]的表达水平;并采用苏木素—伊红(HE)染色进行组织病理学观察;利用串联质谱标签技术(tandem mass tag,TMT),筛选正常对照组、模型组和羟基红花黄色素A各剂量组之间的差异表达蛋白(differentially expressed proteins,DEPs),并借助Uniprot数据库以及微生信在线工具等对其进行GO和KEGG富集分析。结果(1)与正常对照组相比,模型组大鼠肝脏系数、肝功能指标、MDA含量以及促炎因子表达水平均显著升高(P<0.05),SOD活力显著降低(P<0.05);与模型组相比,羟基红花黄色素A各剂量组大鼠肝脏系数、中高剂量组ALP含量以及各剂量组ALT、AST、MDA含量和促炎因子的表达水平均显著降低(P<0.05),SOD活力显著升高(P<0.05)。(2)模型组与正常对照组共筛选出243个DEPs,其中上调蛋白188个,下调蛋白55个;羟基红花黄色素A各剂量组与模型组共筛选出104个DEPs,其中上调蛋白37个,下 Objective To investigate the protective mechanism of Hydroxysafflor yellow A(HSYA)on acute liver injury(ALI)based on proteomic method.Methods Male Wistar rats were randomly divided into the normal control group,the carbon tetrachloride(CCl 4)model group and the HSYA low,medium and high dose groups[10,20,40 mg/(kg·d)],with 10 rats in each group.The rats in the normal control group and the model group were intraperitoneally injected with normal saline,and the rat in the HSYA group was intraperitoneally injected with different concentrations for 8 days.One hour after the administration on the 8th day,the rats in the other groups were intraperitoneally injected with 50%CCl 4 peanut oil solution(0.1mL/100g)at one time.ALI model was established,and the rats in the normal control group was injected with the same volume of peanut oil.After 24 hours,the liver coefficient of rats was dissected and calculated;detectioned of serum liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)],oxidation indexes[superoxide dismutase(SOD)activity,malondialdehyde(MDA)]and inflammatory factors(TNF-α,IL-1β,IL-6);hematoxylin-eosin staining(HE)was used for histopathological observation;Using tandem mass tag(TMT),the differentially expressed proteins(DEPs)among the normal control group,the model group and the HSYA administration group were screened,and GO and KEGG enrichment analysis was carried out with the help of Uniprot database and WeChat online tools.Results(1)Compared with the normal control group,the liver coefficient,liver function index,MDA content and expression level of pro-inflammatory factors in the model group were significantly increased,and the SOD activity was significantly decreased(P<0.05).Compared with the model group,the liver coefficient of the rats in each dose group of HSYA,the content of ALP in the middle and high dose groups,the content of ALT,AST,MDA and the expression levels of pro-inflammatory factors in each dose group were significantly decreased,a
作者 侯祥梅 张子英 马月宏 金蓉 乙兵 杨冬冬 马丽杰 HOU Xiangmei;ZHANG Ziying;MA Yuehong;JIN Rong;YI Bing;YANG Dongdong;MA Lijie(Inner Mongolia Key Laboratory of Molecular Biology,Inner Mongolia Medical University,Hohhot 010059,China)
出处 《环球中医药》 CAS 2023年第1期46-53,共8页 Global Traditional Chinese Medicine
基金 国家自然科学基金(81960759) 内蒙古自治区自然科学基金(2020MS08040)。
关键词 急性肝损伤 羟基红花黄色素A 红花 蛋白组学 差异表达蛋白 炎症因子 氧化应激 Acute liver injury Hydroxysafflor yellow A Safflower Proteomics Differentially expressed proteins Inflammatory factor Oxidative stress
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