Zuo Yi-Nan, He Xue-Ling, Shi Xue-Ni, Wei Shi-Hang, Yin Hai-Lin
College of Life Sciences, Sichuan University, Chengdu 610065, China.
Laboratory Animal Center, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2017 May;48(3):368-372.
To investigate the correlation between the absolute quantification of the microRNAs (miR-122, miR-451, miR-92a, miR-192) in serum during acute liver injury and the extent of liver injury on rat models of CCl induced acute liver injury and mice models of acetaminophen (APAP) induced acute liver injury. Furthermore, to investigate the correlation between the absolute quantification of microRNAs in serum and the drug induced liver injury pathological scoring system (DILI-PSS).
The acute liver injury model in rat by CCl (1.5 mL/kg), and the acute liver injury model in mice by APAP (160 mg/kg) were established. The serum at different time points on both models were collected respectively. The absolute quantification of microRNAs in serum were detected by using MiRbay SV miRNA Assay kit. Meanwhile, the pathological sections of liver tissue of the mice at each time point were collected to analyze the correlation between microRNAs and the degree of liver injury.
In CCl-induced rat acute liver injury model and APAP induced mouse acute liver injury, miR-122 and miR-192 appeared to be rising significantly, which remained the highest level at 24 h after treatment, and declined to the normal level after 72 h. In CCl-induced rat acute liver injury model, the change of miR-92a was fluctuated and had no apparent rules, miR-451 declined gradually, but not obviously. In mice acute liver injury model induced by APAP, miR-92a and miR-451 in the progress of liver injury declined gradually, reached the lowest point at 48 h, and then recovered. The result of correlation analysis indicated that miR-122 and miR-192 presented a good positive correlation with the DILI-PSS ( =0.741 3, <0.05; =0.788 3, <0.01).
The absolute quantification of miR-122 and miR-192 in serum has the highest level in 24 h, then decrease in 72 h, in both drug-induced and chemical liver injury. In addition, both the two microRNAs have good correlation with DILI-PSS in APAP-induced liver injury models.
研究四氯化碳（CCl）诱导的大鼠急性肝损伤模型和对乙酰氨基酚（APAP）诱导的小鼠急性肝损伤模型中，急性肝损伤期间血清中微小RNA（miR-122、miR-451、miR-92a、miR-192）的绝对定量与肝损伤程度之间的相关性。此外，研究血清中微小RNA的绝对定量与药物性肝损伤病理评分系统（DILI-PSS）之间的相关性。
建立CCl（1.5 mL/kg）诱导的大鼠急性肝损伤模型和APAP（160 mg/kg）诱导的小鼠急性肝损伤模型。分别在两个模型的不同时间点采集血清。使用MiRbay SV miRNA检测试剂盒检测血清中微小RNA的绝对定量。同时，收集各时间点小鼠肝组织的病理切片，分析微小RNA与肝损伤程度之间的相关性。
在CCl诱导的大鼠急性肝损伤模型和APAP诱导的小鼠急性肝损伤中，miR-122和miR-192明显升高，在治疗后24小时达到最高水平，72小时后降至正常水平。在CCl诱导的大鼠急性肝损伤模型中，miR-92a的变化波动且无明显规律，miR-451逐渐下降，但不明显。在APAP诱导的小鼠急性肝损伤模型中，肝损伤过程中miR-92a和miR-451逐渐下降，在48小时达到最低点，然后恢复。相关性分析结果表明，miR-122和miR-192与DILI-PSS呈良好的正相关（r = 0.741 3，P < 0.05；r = 0.788 3，P < 0.01）。
在药物性和化学性肝损伤中，血清中miR-122和miR-192的绝对定量在24小时达到最高水平，然后在72小时下降。此外，在APAP诱导的肝损伤模型中，这两种微小RNA与DILI-PSS均具有良好的相关性。
