| Objective To explore the effect of Salvia miltiorrhiza on tumor microvasculogenesis in hepatocellular carcinoma rat model by observing the level of serum HIF-1α and VEGF, the expression of HIF-1α and VEGF, and micro vessel density (MVD) of liver cancer tissue.Methods50Wistar rats were randomly divided into five groups: normal group, model group, low dose (0.1g/mL), middle dose (0.2g/mL) and high dose (0.4g/mL) of Salvia group. In addition to normal group, the other four groups were induced into hepatocellular carcinoma (HCC) models by intermittent small doses of DEN. Since15th week of the experiment, different concentrations of Salvia miltiorrhiza were given to the Salvia groups by gavage, according to the weight of5ml/kg dose. Normal group and model group were given the same amount of saline. The rats were sacrificed at21th week of the experiment. The level of serum HIF-1α and VEGF were detected by enzyme-linked immunosorbent assay. The expression of HIF-1α and VEGF and MVD of liver cancer tissue were studied by immunohistochemical assay.Results1. The difference of the level of serum HIF-la and VEGF between the various groups.1.1The concentrations of serum HIF-1α and VEGF in normal group were17.20+2.94and78.65+8.49, respectively. Compared with the normal group, the concentrations of serum HIF-1α and VEGF in model group were increased significantly (P <0.01), which were44.61+6.85and379.18+24.63, respectively.1.2Compared with the model group, the concentrations of serum HIF-1α of the Salvia groups were decreased significantly, which were38.67±6.44,32.96±4.79and26.74±7.30in low dose group, middle dose group, and high dose group, respectively. The concentrations of serum VEGF of the Salvia groups were also reduced obviously, which were312.18±24.00,280.47±24.32and258.65+22.21in low dose group, middle dose group, and high dose group, respectively.(P <0.01)2. The effect of different dose of Salvia miltiorrhiza on microvessel density of rat liver cancer tissue.2.1The microvessel density of liver tissue in normal group was18.50±5.84. Compared with the normal group, the microvessel density of liver cancer tissue of model group was increased significantly (P <0.01), which was39.25±8.21.2.2The microvessel density of liver cancer tissue of low-dose, middle-dose and high-dose of Salvia groups were36.11±4.49,30.56±4.04and28.00±4.03, respectively. Compared with the model group, the microvessel density was reduced significantly in middle-dose and high-dose groups. But the low-dose group had no statistical significance.3. The effect of different dose of Salvia miltiorrhiza on the expression of HIF-1α and VEGF of rat liver cancer tissue. 3.1The expression of HIF-1α and VEGF in liver tissue of normal group was not obvious. There were high expression of HIF-1α and VEGF in liver cancer tissue of the model group. Both had significant difference (P<0.01).3.2Compared with the model group, the expression of HIF-la and VEGF in liver cancer tissue of the low-dose, middle-dose and high-dose of Salvia groups were gradually reduced. There were significant difference between middle-dose, high-dose and model groups.4. The correlation analysis between the level of serum HIF-1α and VEGF and MVD of rat liver cancer tissue.The concentrations of serum HIF-la and VEGF (r=0.841, P=0.000), the concentrations of serum VEGF and the MVD of rat liver cancer tissue (r=0.748, P=0.000), the concentrations of serum HIF-la and the MVD of rat liver cancer tissue (r=0.643, P=0.000), they were all significantly positively correlated.Conclusion1. The hepatocellular carcinoma rat models were induced by diethylnitrosamine (DEN) in the experiment. In the model groups, the microvessel density of liver cancer tissue was increased significantly, there were high expression of HIF-lα and VEGF in liver cancer tissue, and the concentrations of serum HIF-lα and VEGF were increased. The results showed that the HIF-la and VEGF play an important role in occurrence and development of hepatocellular carcinoma during rat hepatocellular carcinogenesis, the mechanism may be associated with the promotion of tumor angiogenesis.2. Different doses of Salvia miltiorrhiza could reduce the expression of HIF-1α and VEGF and MVD in liver cancer tissue, the level of serum HIF-1α and VEGF, especially the middle and high dosage group.3. Salvia miltiorrhiza could inhibit tumor angiogenesis in hepatocellular carcinoma rat model. One of the mechanisms may be associated with that Salvia inhibited expression of HIF-1α and decreased VEGF synthesis. |
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