Mechanism study of interfering with circCPSF1 expression to counteract the impact of anti-tuberculosis drug-in-duced liver injury
Objective This study explores the correlation between circCPSF1 and Anti-tuberculosis drug-in-duced liver injury(ADLI)from both population and cells,and explores the mechanism of circCPSF1 affecting the occurrence of ADLI through sponge combined with miR-21.Methods We collected the group of patients who suffered liver injury after tuberculosis treatment at Shijiazhuang Fifth Hospital from September 1,2022 to September 1,2023 as the ADLI group,and match them with non-ADLI patients who did not suffer liver injury by gender and age in a 1∶1 ratio,with a total of 125 cases in each group.Real-time fluorescence quanti-tative PCR(RT-qPCR)detects the relative expression of circCPSF1 and analyzes its correlation with liver damage.The liver damage cell model was constructed with the combination of isoniazid(INH),rifacin(RFP)and pyrazinamide(PZA)and was expressed or attenuated.The morphological changes of cells were observed by HE staining.The expression of circCPSF1 and miR-21 was detected by RT-qPCR.The level of NF-κB protein was detected by western blot.The expression levels of alanine aminotransferase(ALT),as-partate aminotransferase(AST),nuclear factor κB(NF-κB),tumor necrosis factor(TNF-α)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay(ELISA).The binding of circCPSF1 to miR-21 was verified by fluorescence pigmentation enzyme reporter gene experiment.Results Compared with non-ADLI,the relative expression of circCPSF1 in the serum of the ADLI group was significantly reduced(P＜0.05),which was negatively correlated with liver function indicators.In the ADLI cell model,the expression of circCPSF1 is lowered,and the expression of miR-21 was adjusted up(P＜0.05).Overexpression of circ-CPSF1 and knocking down miR-21 can inhibit the expression levels of NF-κB,TNF-α and IL-6(P＜0.05).The genetic experimental results of luciferase report showed that circCPSFl is combined with miR-21.Conclu-sion At the population and cell level,circCPSFl shows a large difference in expression in ADLI and can play a classic sponge role in regulating miR-21 to mediate the expression of inflammatory factors and affect liver cell damage.
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