The Relevant Research Between HMGB1 And Acute Drug-induced Liver Injury

Objective : Acute drug-induced liver injury animal models were prepared by intragastric administration of acetaminophen solution,and the changes in serum and liver tissue levels of HMGB1 and liver injury indicators in ADILI animal models were studied,and the role of HMGB1 in the process of acute drug-induced liver injury was explored.Changes,and its correlation with liver injury indicators,further clarify the correlation between HMGB1 and acute drug-induced liver injury.Method:1.Select 25 male SD rats,and after adaptive feeding for 1 week,they are randomly divided into 2 groups: healthy control group(10)and ADILI model group(10).Animal models of acute drug-induced liver injury were prepared by gavage of paracetamol solution in the model group;animals in the healthy control group were gavage with 200 microliters of normal saline.After the preparation of the model was completed,the animal models of acute drug-induced liver injury were prepared at different time periods(0,3,6).,9,12,24,48,96h)Collect experimental animal venous blood specimens,and take experimental animal liver tissue specimens at 24 h and 96 h for model verification and experimental research.2.The whole blood samples of experimental animals were centrifuged to obtain serum,and the ELISA method was used to detect the serum HMGB1 level of rats in different time periods,and the automatic biochemical analyzer method was used to detect the serum liver injury indexes ALT,AST,ALP,TBIL And DBIL levels.3.The liver tissues of experimental animals were stained with histology,and the histopathology and HMGB1 expression level of the liver were observed through an optical microscope.4.Use SPSS22.0 statistical analysis software for data analysis;all indicators have been tested for normality and homogeneity of variances.Measurement data conforming to the normal distribution are expressed as mean ± standard deviation;two independent samples are used for comparison between the two groups.Test;correlation analysis adopts spearman correlation analysis.P<0.05 indicates that the difference is statistically significant.Result:1.Validation of acute drug-induced liver injury model(1)Analysis of liver injury indicatorsThere are significant differences in the levels of liver injury indexes ALT,AST,ALP,TBIL and DBIL between the healthy control group and the ADILI model group at different time periods.Among them,the expression of ALT,AST and TBIL is highest at 24h;the expression of ALP is highest at 3h and then begins to decline,Suggesting that the ADILI model has liver damage.(2)Histological analysisUnder the HE staining optical microscope,the liver tissues of the ADILI model rats showed watery degeneration,intracellular swelling and looseness,and inflammatory pathological changes such as cytoplasmic eosin staining.The liver tissue of the healthy control group was normal,indicating that the liver tissue of the healthy control group was normal.It suggests that the animals in the ADILI model group have acute liver injury.2.Study on the correlation between HMGB1 and acute drug-induced liver injury(1)Analysis of the difference in serum HMGB1 levels between the ADILI model group and the healthy control group at different time periodsSerum HMGB1 levels in the ADILI model group showed a gradual increase in different time periods(0,3,6,9,12,24,48,96h).Compared with the healthy control group,there was no statistical difference in serum HMGB1 levels at 0 and 3 hours.Scientific significance(p>0.05),the comparison of serum HMGB1 levels at 6,9,12,24,48,96 h,the difference was statistically significant(p<0.01).(2)Differential analysis of HMGB1 expression in liver tissues of ADILI model group and healthy control groupThe 96 h liver tissue immunohistochemical staining in the ADILI model group showed statistically significant differences in the expression of HMGB1 compared with the healthy control group(p<0.05).(3)Correlation analysis of serum HMGB1 level and liver injury indexes in ADILI model groupCorrelation analysis between serum HMGB1 levels and ALT,AST,ALP,TBIL and DBIL levels in the ADILI model group at different time points showed that the serum HMGB1 levels in the ADILI model group were correlated with ALT and AST at these three time points at 0,3,and6 h.There was no significant correlation between ALP,TBIL and DBIL levels(p>0.05);serum HMGB1 levels in the ADILI model group were positively correlated with ALT and AST levels at9,12,24,48,96h(p<0.05).Conclusion:1.The serum HMGB1 level of ADILI model rats was significantly increased,which was significantly higher than that of the healthy control group at 6,9,12,24,48,96 h time points.2.The expression of HMGB1 in the liver tissue of the 24 h and 96 h model group was higher than that of the healthy control group.The serum and liver tissue levels of HMGB1 were increased in acute drug-induced liver injury.3.There is a correlation between the changes in serum HMGB1 levels at different time points in the ADILI model and liver injury indicators.It is speculated that HMGB1 has abnormal changes in serum levels before the conventional liver injury indicators of acute drug-induced liver injury are abnormal.It is speculated that it can be used to monitor acute drug-induced liver injury.A biomarker of injury occurrence,development and change.