Abstract: Objective:To investigate the effects of berberine combined with simvastatin on the expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), interleukin-18 (IL-18) and interleukin-10 (IL-10) in the thoracic aorta tissue of the atherosclerosis (AS)model rats, and to elucidate the mechanism of anti-atherosclerosis of berberine combined with simvastatin. Methods:A total of 48 rats were divided into control group, model group, simvastatin group, low, middle and high doses of berberines combined with simvastatin groups(n=8).The serum and thoracic aorta tissue of the rats were obtained 4 weeks after adminstration. HE staining was used to observe the pathomorphology of the thoracic aorta of the rats in various goups; ABC-double antibody sandwich ELISA method was used to detect the serum VEGF, TGF-β1, IL-18 and IL-10 of the rats in various groups; automatic biochemistry analyzer was performed to determine the levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterin (LDL-C), high density lipoprotein cholesterin (HDL-C) of the rats in various groups. The expression levels of VEGF, TGF-β1, IL-18, and IL-10 proteins in the aortic tissue of the rats in various groups were determined by immunohistochemistry. Results:The HE results showed that compared with control group, the intima of aorta of the rats in model group was significantly thickened, lipid deposition was observed inside and outside the cells, necrosis was observed under the intima, plaques and irregularities were observed in the inner wall, and the vascular cavity was narrowed;compared with model group, in high dose of berberine combined with simvastatin group, there was no obvious plaque on the arterial wall, and the intimal thickening was significantly improved. Compared with model group, the serum TC, TG, and LDL-C levels of the rats in simvastatin group and different doses of berberine combined with simvastatin group were significantly decreased (P< 0.05 or P< 0.01), and the serum HDL-C level was significantly increased (P< 0.05). The results of ABC-ELISA showed that compared with model group, the serum VEGF and IL-18 levels in simvastatin and different doses of berberine combined with simvastatin groups were significantly decreased (P<0.05 or P<0.01),and the serum TGF-β1 and IL-10 levels were significantly increased (P<0.05). The results of immunohistochemistry showed that compared with model group,the expression level of IL-18 protein in thoracic aorta tissue of the rats in simvastatin group was significantly decreased(P<0.05),and the expression level of TGF-β1 protein was significantly increased(P<0.05); the expression levels of VEGF and IL-18 proteins in the thoracic aorta tissue of the rats in different doses of berberine combined with simvastatin groups were significantly reduced (P<0.05),and the expression levels of TGF-β1 and IL-10 proteins were significantly increased (P<0.05). Conclusion:Berberine combined with simvastatin could control AS via the up-regulation of the expression levels of VEGF and IL-18 proteins and the down-regulation of the expression levels of TGF-β1 and IL-10 proteins in serum and thoracic aorta tissue of rats.

Key words: berberine, simvastatin, atherosclerosis, vascular endothelial growth factor, transforming growth factor-β1, interleukin-18, interleukin-10