蛇床子素调节JAK2/STAT3信号通路对乙型肝炎病毒大鼠肝功能及肝纤维化影响的研究OA

Objective To investigate the effects of osthole(Ost)adjusting the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway on liver function and liver fibrosis in hepatitis B virus(HBV)rats.Methods An HBV rat model was established.The successfully modeled rats were divided into model(normal saline),low-(10 mg·kg-1 Ost),medium-(20 mg·kg-1 Ost)and high-dose(40 mg·kg-1 Ost)experimental groups,JAK2 pathway activator group(40 mg·kg-1 Ost+4.0 mg·kg-1 Coumermycin A1)with 12 rats in each group,and another 12 rats were selected as blank control group(normal saline).Liver function indicators were detected using an automatic biochemical analyzer.Inflammatory cytokines,fibrotic markers,and levels of hepatitis B surface antigen(HBsAg)and hepatitis B e antigen(HBeAg)were measured by enzyme-linked immunosorbent assay(ELISA).Hepatitis B virus deoxyribonucleic acid(HBV-DNA)content was detected by real-time quantitative polymerase chain reaction(real-time qPCR).Hematoxylin-eosin(HE)staining was used to observe pathological changes in liver tissue,and Masson staining was used to observe liver fibrosis.Western blot was employed to detect the expression of JAK2/STAT3 pathway-related proteins.Results The levels of alanine aminotransferase(ALT)in the blank control group,model group,low-,medium-,and high-dose experimental groups and JAK2 pathway activator group were(30.15±6.29),(78.56±7.92),(62.33±7.16),(50.08±6.88),(37.89±6.54)and(70.46±7.53)U·L-1,respectively;the levels of aspartate aminotransferase(AST)were(68.52±10.63),(115.37±12.03),(102.65±11.54),(85.97±11.19),(72.11±10.87)and(109.83±11.66)U·L-1,respectively;the levels of interleukin-6(IL-6)were(62.78±11.94),(146.32±14.76),(121.53±13.05),(95.67±12.79),(70.29±12.32)and(135.62±13.82)pg·mL-1,respectively;the levels of HBsAg were(0.00±0.00),(3120.54±320.16),(2 436.83±296.51),(1 653.28±281.03),(1 026.49±273.64)and(2 903.66±308.59)U·mL-1,respectively;the ratios of phosphorylated(p)-JAK2/JAK2 were 0.29±0.04,0.77±0.09,0.63±0.07,0.50±0.06,0.35±0.05 and 0.72±0.08,respectively;the ratios of p-STAT3/STAT3 were 0.41±0.04,0.86±0.09,0.72±0.07,0.59±0.06,0.46±0.05 and 0.79±0.08,respectively.Comparisons between the model group and the blank control group,between the low-,medium-,and high-dose experimental groups and the model group,and between the JAK2 pathway activator group and the high-dose experimental group all showed statistically significant differences in the above indicators(all P＜0.05).Conclusion Ost may inhibit liver fibrosis in HBV rats and improve liver function by suppressing the JAK2/STAT3 pathway.