Found programs:
Authors:Liu Xiaoqing; Lu Huanbing; Liu Ruixue
Keywords:acetaminophen;drug-induced liver injury;Bruton's tyrosine kinase;NF-κB;NLRP3
DOI:10.19405/j.cnki.issn1000-1492.2020.08.006
〔Abstract〕 Objective To observe the dynamic changes of Bruton's tyrosine kinase(Btk), phosphorylated Btk(p-Btk), nuclear factor κB(NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) in acute liver injury induced by acetaminophen(APAP) in mice, and preliminarily explore the role of Btk in acute liver injury induced by APAP. Methods 54 mice were randomly divided into 9 groups, including control group, APAP 0.5 h group, APAP1 h group, APAP3 h group, APAP6 h group, APAP12 h group, APAP24 h group, APAP36 h group and APAP48 h group. After fasting for 12 h, mice in the corresponding groups were sacrificed after a single intraperitoneal injection of APAP(300 mg/kg) for 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h, 36 h and 48 h. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured by chemical method. Liver tissue damage was observed by HE staining. IL-1β and TNF-α in liver tissue homogenate were measured by ELSIA.The expression of Btk, p-Btk,NF-κB and NLRP3 was determined by Western blot. Results Compared with the control group, serum ALT(F=100.968,P=0.000), AST(F=73.539,P=0.000), liver necrosis degree(F=29.845,P=0.000), liver Btk(F=441.280,P=0.000), p-Btk(F=1 323.022,P=0.000), NF-κB(F=133.125,P=0.000), NLRP3 levels(F=820.095,P=0.000) and the content of IL-1β(F=8.643,P=0.000), TNF-α(F=20.545,P=0.000) all changed. Among them, the various kinds index of 24 h was respectively the highest. Conclusion Liver injury induced by single intraperitoneal injection of APAP shows dynamic changes, which pathogenesis may be related to APAP-induced activation of Btk, resulting in formation of NLRP3, activation of NF-κB and increase of inflammatory factors.