Study On The Clinical And Molecular Mechanism Of Carbamazepine's Effect On The Index Of APRI And Fib-4

Objective:To investigate the clinical and molecular mechanisms of the effects of carbamazepine on liver fibrosis non-invasive testing indicators: the aspartate transaminase to platelet ratio index(APRI)and fibrosis index based on four factors(Fib-4).Methods: 1.Through the Hospital Information System(HIS),we retrospectively analyzed the clinical information of inpatients treated with carbamazepine in a Third Grade Class A Hospital in Guangxi Zhuang Autonomous Region,China.According to the inclusion and exclusion criteria,we collected basic information,diagnostic information,alanine aminotransferase(ALT),aspartate aminotransferase(AST),platelet(PLT)and other test indicators to calculate its APRI and FIB-4 index.We classified patients with APRI> 0.5 and FIB-4> 1.45 into the liver fibrosis group,and grouped patients with APRI?0.5 or FIB-4?1.45 into the control group.We compared the changes of APRI and FIB-4 index after the treatment of carbamazepine in the two groups.2.After 24 hours of intervention with different concentrations of carbamazepine(CBZ)on the activated hepatic stellate cell T6 model induced by platelet derived growth factor(PDGF),Western blot was used to analyze the differences of expression of collagen I / COL1A1 and NIX/Bnip3-L protein of mitophagy in each group of cell model.Quantitative real-time quantitative reverse transcription polymerase chain reaction(q RT-PCR)was used to ananlyze the expression of collagen I m RNA and Nix m RNA in each group and the apoptosis rate of each group was compared by flow cytometry.Results: 1.94 patients treated with carbamazepine were collected.According to the inclusion and exclusion criteria,19 patients were included in the study,including 15 male patients and 4 female patients.Based on the inclusion criteria,8 patients were included in the fibrosis group,and 11 patients were included in the control group.After treatment with carbamazepine,the Apri index decreased by 73.78%(t = 2.403,P = 0.047 < 0.05)and FIB-4 index decreased by 52.39%(t = 4.24,P = 0.02 < 0.05).However,there was no significant difference in APRI(t= 0.328,P=0.750>0.05)and fib-4 index(t=1.474,P=0.171>0.05)after carbamazepine treatment in the control group.2.The experimental results showed that the expression level of COL1A1 m RNA and protein in CBZ treated group decreased significantly,while the expression level of Nix m RNA and protein also decreased.Within a certain concentration of carbamazepine,there was a negative correlation between the expression of COL1A1 protein and the expression of NIX protein,and the apoptosis rate in the CBZ treatment group was increased significantly(P <0.05).Conclusion: 1.After the treatment with carbamazepine(CBZ),the indexes of liver fibrosis: Apri and FIB-4 index can be significantly lower than that before the treatment.2.Carbamazepine can reduce the expression of T6 collagen in activated hepatic stellate cells and increase its apoptosis rate,and its effect may be related to the down-regulation of NIX m RNA and protein expression.3.The above clinical and molecular mechanism studies suggest that carbamazepine has the potential to become a new anti-fibrotic drug,but further and in-depth research is still needed.