Abstract: Objective To investigate the effect of Congxin Lunzhi Fang (CXLZF) for improving atherosclerosis (AS) and explore its therapeutic mechanism. Methods Thirty ApoE-/- mice were fed on high-fat diet (HFD) to establish AS models, which were randomized equally into model group, low- , medium- and high-dose CXLZF groups (daily dose 4.5, 9, and 18 g/kg, respectively), and simvastatin (5 mg/kg daily) group, with 6 male C57BL/6 mice fed a normal diet as the control group. The mice in the control and model groups were gavaged with normal saline, and those in the treatment groups were gavaged with the indicated drugs for a treatment course of 12 weeks. The changes of atherosclerotic plaque and liver pathologies were observed using oil-red O, HE and Masson staining, and blood lipid profiles and serum levels of glucose, Alanine aminotransferase ( ALT) and Aspartate aminotransferase (AST) of the mice were examined. The protein expressions of ACE2 and E-selectin were determined with Western blotting. Drug-containing serum was collected from SD rats gavaged with CXLZF for treatment of human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL)-induced injury, and the protein expression of ACE2 in the cells was determined. Results In ApoE-/- mice, CXLZF at all the 3 doses significantly reduced the plaque area and increased the collagen content in atherosclerotic plaque, indicating improved plaque stability. CXLZF treatment, especially at the high dose, also significantly reduced the levels of serum lipids (P<0.05). CXLZF significantly lowered serum ALT and AST levels, mitigated hepatocyte steatosis (P<0.05), increased the protein expression of ACE2 and down-regulated E-selectin expression (P<0.05) in the mice. In HUVEC cultures, CXLZF-containing serum (5%, 10%, and 20%) significantly up-regulated the cellular expression of ACE2 protein (P<0.05). Conclusion CXLZF relieves aortic atherosclerosis in ApoE-/- mice possibly by regulating ACE2 protein.

Key words: Congxin Lunzhi Fang; arotic atherosclerosis; angiotensin-converting enzyme 2