Abstract: Objective To investigate the effects of cannabinoid receptor 2 agonist AM1241 on the proliferation, activation and apoptosis of rat hepatic stellate cells (HSC-T6) induced by TGF-β1 and the related mechanism. Methods HSC-T6 cells were treated with different concentrations of AM1241 (0, 20, 40, 80 and 160 μmol/L) for 24 hours. Cells of each group were given TGF-β1 (5 μg/L) simultaneously. The effect of AM1241 on the proliferation of HSC-T6 cells was detected by CCK-8 assay. HSC-T6 cells were divided into negative control group, TGF- β1 group, 30 μmol/L AM1241 group and 60 μmol/L AM1241 group. Flow cytometry was used to detect the effect of AM1241 on HSC-T6 apoptosis. HSC-T6 cells were divided into negative control group, TGF- β1 group and 30 μmol/L AM1241 group (according to CCK-8 assay). IC50 was calculated. The protein levels of α-smooth muscle actin (α-SMA), basic fibroblast growth factor (bFGF), apoptosis-related protein Bax, cleaved caspase-3 and phosphorylated c-Jun amino terminal kinase (p-JNK) were detected by Western blot assay. Results Compared with TGF-β1 group, AM1241 showed an inhibitory effect on the proliferation of HSC-T6 cells in a dose-dependent manner (P＜0.05). When IC50 of AM1241 was 27 μmol/L, the apoptosis rates of HSC-T6 were significantly higher in AM1241 groups (30 and 60 μmol/L) than those in TGF - β1 group, and it was significantly higher in 60 μmol/L AM1241 group than that of 30 μmol/L AM1241 group (P＜0.05). The protein levels of α-SMA and bFGF were significantly lower in 27 μmol/L AM1241 group than those in the TGF-β1 group (P＜0.05). The protein levels of Bax, cleaved caspase-3 and p-JNK were significantly upregulated in AM1241 group than those of the TGF-β1 group (P＜0.05). Conclusion The cannabinoid receptor 2 agonist AM1241 can inhibit the proliferation and activation of HSC-T6 cells induced by TGF-β1 and promote the apoptosis of HSC-T6 cells, which may be related to the JNK pathway.

Key words: liver cirrhosis, hepatic stellate cells, receptor, cannabinoid, CB2, transforming growth factor beta1; apoptosis, liver fibrosis, AM1241