急性药物性肝损伤血清miR-122与肝损伤指标相关性研究
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摘要
目的探讨急性药物性肝损伤(acute drug-induced liver injury, ADILI)模型血清miR-122与肝损伤指标的相关性。方法选用6～8周龄雄性小鼠随机分为对照组和模型组,模型组通过对乙酰氨基苯酚灌胃法制备ADILI动物模型,模型制备成功后,检测实验小鼠血清AST、ALT、ALP、TBIL、miR-122表达水平;对实验结果进行统计学分析。结果 ADILI模型组在8、16、24、48 h时4个时间点血清miR-122水平与对照组比较差异有统计学意义(P<0.05),其余时间点两者水平差异无统计学意义(P>0.05)。ADILI模型组在8、16、24 h时3个时间点血清miR-122水平与ALT、AST水平呈正相关,其余时间点无相关性。ADILI模型组不同时间点血清miR-122水平与ALP、TBIL水平无相关性。结论 ADILI模型血清miR-122表达水平明显升高,与肝损伤指标AST、ALT表达水平呈正相关,与肝损伤指标ALP、TBIL表达水平无相关性。
Objective To investigate the correlation between serum miR-122 and liver injury index in acute drug-induced liver injury(ADILI) rats. Methods Male rats(6 to 8 week-old) were randomly divided into control group and model group. The model group was induced to ADILI model by Acetaminophenol gastric irrigation. After the model validation succeed, the expression levels of AST, ALT, ALP, TBIL, miR-122 were tested in in rats blood. Then the results were analyze by statistical method. Results There was significant difference in expression level of serum miR-122 at 4 time points in the 8 th, 16 th, 24 th and 48 th hours between ADILI model group and control group(P<0.05), there was no difference in the other time points(P>0.05). The expression level of serum miR-122 was positively correlated with serum ALT and AST levels at 8 th, 16 th, 24 th hours in ADILI model group, there was no correlation in the other time points(P>0.05). The expression level of serum miR-122 was not correlated with serum ALP and TBIL levels in the different time points in ADILI model group. Conclusion The serum expression level of miR-122 was significantly increased in ADILI model rats, which was positively correlated with the expression level of AST and ALT, and had no correlation with the expression level of ALP and TBIL.
Objective To investigate the correlation between serum miR-122 and liver injury index in acute drug-induced liver injury(ADILI) rats. Methods Male rats(6 to 8 week-old) were randomly divided into control group and model group. The model group was induced to ADILI model by Acetaminophenol gastric irrigation. After the model validation succeed, the expression levels of AST, ALT, ALP, TBIL, miR-122 were tested in in rats blood. Then the results were analyze by statistical method. Results There was significant difference in expression level of serum miR-122 at 4 time points in the 8 th, 16 th, 24 th and 48 th hours between ADILI model group and control group(P<0.05), there was no difference in the other time points(P>0.05). The expression level of serum miR-122 was positively correlated with serum ALT and AST levels at 8 th, 16 th, 24 th hours in ADILI model group, there was no correlation in the other time points(P>0.05). The expression level of serum miR-122 was not correlated with serum ALP and TBIL levels in the different time points in ADILI model group. Conclusion The serum expression level of miR-122 was significantly increased in ADILI model rats, which was positively correlated with the expression level of AST and ALT, and had no correlation with the expression level of ALP and TBIL.
引文
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[18] BANDIERA S, PFEFFER S, BAUMERT T F, et al. miR-122--a key factor and therapeutic target in liver disease [J]. J Hepatol, 2015, 62(2): 448-457. DOI: 10.1016/j.jhep.2014.10.004.
[19] SZABO G, BALA S. MicroRNAs in liver disease [J]. Nat Rev Gastroenterol Hepatol, 2013, 10(9): 54-552. DOI: 10.1038/nrgastro.2013.87.
[20] 王雁, 汤纳平, 富欣, 等. 对乙酰氨基酚诱导的急性肝损伤大鼠血浆miR·122表达的变化[J]. 中国药理学与毒理学杂志, 2013, 27(5): 854-859. DOI: 10.3867/j.issn.1000-3002.2013.05.015.
[2] KERR T A, KORENBLAT K M, DAVIDSON N O. MicroRNAs and liver disease [J]. Transl Res, 2011, 157(4): 241-252. DOI: 10.1016/j.trsl.2011.01.008.
[3] WAIDMANN O, BIHRER V, PLELI T, et al. Serum microRNA-122 levels in different groups of patients with chronic hepatitis B virusinfection [J]. J Viral Hepat, 2012, 19(2): e58-e65. DOI: 10.1111/j.1365-2893.2011.01536.x.
[4] DING X, DING J, NING J, et al. Circulating microRNA-122 as a potential biomarker for liver injury [J]. Mol Med Rep, 2012, 5(6): 1428-1432. DOI: 10.3892/mmr.2012.838.
[5] BALA S, PETRASEK J, MUNDKUR S, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver disease [J]. Hepatology, 2012, 56(5): 1946-1957. DOI: 10.1002/hep.25873.
[6] KALAKI-JOUYBARI F, SHANAKI M, DELFAN M, et al. High-intensity interval training (HIIT) alleviated NAFLD feature via miR-122 induction in liver of high-fat high-fructose diet induced diabetic rats [J]. Arch Physiol Biochem, 2018, 10(13): 1-8. DOI: 10.1080/13813455.2018.1510968.
[7] TORRES J L, NOVO VELEIRO I, MANZANEDO L, et al. Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease [J]. World J Gastroenterol, 2018, 24(36): 4104-4118. DOI: 10.3748/wjg.v24.i36.4104.
[8] MCGILL M R, JAESCHKE H. Biomarkers of drug-induced liver injury: progress and utility in research, medicine, and regulation [J]. Expert Rev Mol Diagn, 2018, 18(9): 797-807. DOI: 10.1080/14737159.2018.1508998.
[9] JAMPOKA K, MUANGPAISARN P, KHONGNOMNAN K, et al. Serum miR-29a and miR-122 as potential biomarkers for non-alcoholic fatty liver disease (NAFLD) [J]. Microrna, 2018, 7(3): 215-222. DOI: 10.2174/221153660766618053109330.
[10] AKUTA N, SUZUKI F, KOBAYASHI M, et al.Circulating microRNA-122 levels are important predictor of hepatitis B virus surface antigen seroclearance [J]. J Med Virol, 2018, 90(10): 1586-1592. DOI: 10.1002/jmv.25238.
[11] WANG K, ZHANG S, MARZOLF B, et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury [J]. Proc Natl Acad Sci U S A, 2009, 106(11): 4402-4407. DOI: 10.1073/pnas.0813371106.
[12] COVER C, LIU J, FARHOOD A, et al. Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity [J]. Toxicol Appl Pharmacol, 2006, 216(1): 98-107. DOI: 10.1016/j.taap.2006.04.010.
[13] SU Y W, CHEN X, JIANG Z Z, et al. A panel of serum microRNAs as specific biomarkers for diagnosis of compound- and herb-induced liver injury in rats [J]. PLoS One, 2012, 7(5): e37395. DOI: 10.1371/journal.pone.0037395.
[14] CHALASANI N P, HAYASHI P H, BONKOVSKY H L, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury [J]. Am J Gastroenterol, 2014, 109(7): 950-966. DOI: 10.1038/ajg.2014.131.
[15] BJ?RNSSON E S, BERGMANN O M, BJ?RNSSON H K, et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland [J]. Gastroenterology, 2013, 144(7): 1419-1425. DOI: 10.1053/j.gastro.2013.02.00.
[16] DEVARBHAVI H. An updateon drug-induced liver injury [J]. J Clin Exp Hepatol, 2012, 2(3): 247-259. DOI: 10.1016/j.jceh.2012.05.002.
[17] FONTANA R J, WATKINS P B, BONKOVSKY H L, et al. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct [J]. Drug Saf, 2009, 32(1): 55-68. DOI: 10.2165/00002018-200932010-00005.
[18] BANDIERA S, PFEFFER S, BAUMERT T F, et al. miR-122--a key factor and therapeutic target in liver disease [J]. J Hepatol, 2015, 62(2): 448-457. DOI: 10.1016/j.jhep.2014.10.004.
[19] SZABO G, BALA S. MicroRNAs in liver disease [J]. Nat Rev Gastroenterol Hepatol, 2013, 10(9): 54-552. DOI: 10.1038/nrgastro.2013.87.
[20] 王雁, 汤纳平, 富欣, 等. 对乙酰氨基酚诱导的急性肝损伤大鼠血浆miR·122表达的变化[J]. 中国药理学与毒理学杂志, 2013, 27(5): 854-859. DOI: 10.3867/j.issn.1000-3002.2013.05.015.