天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (6): 593-597.doi: 10.11958/20202948

• 实验研究 • 上一篇    下一篇

血清miR-122和miR-155在丙戊酸钠诱导小鼠仔鼠肝损伤中的表达

崔立华，李杨，白晶，马小焱，王萌，马婧怡，宋佳慧，冯福民   

  1. 华北理工大学公共卫生学院（邮编063210）
  • 收稿日期:2020-10-26 修回日期:2021-02-14 出版日期:2021-06-15 发布日期:2021-06-15
  • 通讯作者: 崔立华 E-mail:15131527204@163.com
  • 基金资助:
    国家自然科学基金资助项目;河北省研究生创新项目

The expression of serum miR-122 and miR-155 in liver injury induced by valproate in mouse offspring

CUI Li-hua, LI Yang, BAI Jing, MA Xiao-yan, WANG Meng, MA Jing-yi, SONG Jia-hui, FENG Fu-min   

  1. School of Public Health, North China University of Science and Technology, Tangshan 063210, China
  • Received:2020-10-26 Revised:2021-02-14 Published:2021-06-15 Online:2021-06-15

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摘要： 目的 探讨血清miR-122和miR-155在丙戊酸钠（VPA）致小鼠仔鼠肝损伤过程中的动态表达及其与肝损 伤的关系。方法 4周龄昆明小鼠按随机数字表法分为对照组30只和实验组56只。实验组又分为7组，分别给予 VPA 375 mg·kg-1·d-1连续灌胃1、3、5、7、14、21和28 d；对照组又分为5组，分别于1、7、14、21和28 d 给予1 mL生理盐 水灌胃，留取血清及肝组织。HE染色观察肝组织病理改变；全自动生化分析仪测定血清丙氨酸转氨酶（ALT）和天冬 氨酸转氨酶（AST）；实时荧光定量聚合酶链式反应（qPCR）检测血清miR-122和miR-155表达水平。结果 肝组织 病理学结果显示，实验组肝细胞出现不同程度的空泡变性。3、5、7 d时肝细胞胞浆内可见少量炎性细胞，21 d时大 量肝细胞变性坏死，28 d时大量肝细胞再生。血清ALT 与AST均呈现下降-升高的趋势。实验组给药后miR-122 表达水平下调，7 d 时降至最低点（下降了 81%），之后上调；而 miR-155 的表达趋势与 miR-122 相反，7 d 时达到最 高点，是对照组的2.88倍。miR-122与ALT和AST呈正相关（rs分别为0.965、0.900，均P＜0.05），miR-155与AST呈 负相关（rs=-0.811，P＜0.05）。结论 miR-122和miR-155参与了VPA药物性肝损伤的发生，有望成为VPA药物性肝 损伤的早期预警指标。

关键词: 丙戊酸, 化学性与药物性肝损伤, 基因表达, 微RNAs, miR-122, miR-155

Abstract: Objective To explore the dynamic expressions of serum miR-122 and miR-155 during the liver injury induced by valproate (VPA) in young mice and their relationship with liver injury. Methods Kunming mice aged 4 weeks were randomly divided into control groups (n=30) and experimental groups (n=56) according to random number table method. Seven experimental groups were given VPA 375 mg·kg-1·d-1 for 1 day, 3 days, 5 days, 7 days, 14 days, 21 days and 28 days consecutively. While five control groups were given 1 mL normal saline daily for 1 day, 7 days, 14 days, 21 days and 28 days. The serum samples and liver tissues of each group were collected. The pathological changes of liver tissue were observed by HE staining. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected by automatic biochemical analyzer. The serum expression levels of miR-122 and miR-155 were detected by real-time quantitative polymerase chain reaction (qPCR). Results The histopathological results showed that liver cells had different degrees of vacuolar degeneration in the experimental groups. A small number of inflammatory cells were observed in the cytoplasm of hepatocytes on the day 3, 5, 7, a large number of hepatocytes were denatured and necrotic on day 21 and regenerated on day 28. It showed a trend of decreasing-increasing on ALT and AST. The expression level of miR-122 was down-regulated in the experimental group after administration, decreased to the lowest level on day 7 (decreased by 81%), and then up-regulated. However, the expression trend of miR-155 was opposite to that of miR-122, reached the peak on day 7, which was 2.88 times that of the control group. MiR-122 was positively correlated with ALT and AST (rs= 0.965 and 0.900, respectively, P＜0.05), while miR-155 was negatively correlated with AST (rs=-0.811, P＜0.05). Conclusion MiR-122 and miR-155 are involved in the occurrence of VPA drug-induced liver injury and are expected to become the early warning indicators.

Key words: valproic acid, chemical and drug induced liver injury, gene expression, microRNAs, miR-122, miR-155