AIM: To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs). METHODS: HSCs isolated from the livers of adult SpragueDawley rats (weighing 400-500 g) by in s...AIM: To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs). METHODS: HSCs isolated from the livers of adult SpragueDawley rats (weighing 400-500 g) by in situ perfusion and purified by single-step density gradient centrifugation with Nycodenz, became activated after 10 days' cultivation. Then the apoptotic rate of HSCs treated with different doses of somatostatin for 72 h, was assayed by acridine orange/ethidium bromide fluorescent staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, transmission electron microscopy and flow cytometry, while the proliferation of HSCs was measured by MTT assay. Furthermore, the mechanisms of somatostatin were investigated by cytodynamic analysis. RESULTS: Somatostatin at the concentration of 10^-6-10^-99 mol/L could decrease the proliferative rate, and promote the apoptosis of activated rat HSCs in a dose-dependent way. Its action was most significant when the concentration reached 10^-6 mol/L or 10^-7 mol/L (P<0.05-0.01). An obvious cell-cycle arrest (G0/G1 arrest) was the important way for somatostatin to exert its action. CONCLUSION: Antiproliferative and proapoptotic effects of low-dose somatostatin on activated rat HSCs can be obtained. These findings reveal its potential antifibrotic action.展开更多
基金Supported by the Scientific Development Programs of Science and Technology Commission Foundation of Shanghai,No.004119047
文摘AIM: To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs). METHODS: HSCs isolated from the livers of adult SpragueDawley rats (weighing 400-500 g) by in situ perfusion and purified by single-step density gradient centrifugation with Nycodenz, became activated after 10 days' cultivation. Then the apoptotic rate of HSCs treated with different doses of somatostatin for 72 h, was assayed by acridine orange/ethidium bromide fluorescent staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, transmission electron microscopy and flow cytometry, while the proliferation of HSCs was measured by MTT assay. Furthermore, the mechanisms of somatostatin were investigated by cytodynamic analysis. RESULTS: Somatostatin at the concentration of 10^-6-10^-99 mol/L could decrease the proliferative rate, and promote the apoptosis of activated rat HSCs in a dose-dependent way. Its action was most significant when the concentration reached 10^-6 mol/L or 10^-7 mol/L (P<0.05-0.01). An obvious cell-cycle arrest (G0/G1 arrest) was the important way for somatostatin to exert its action. CONCLUSION: Antiproliferative and proapoptotic effects of low-dose somatostatin on activated rat HSCs can be obtained. These findings reveal its potential antifibrotic action.
