ABSTRACT
Objective To investigate the effect of safflower yellow injection on atherosclerosis in rabbits with hyperlipidemia.Methods Ninety-six New Zealand rabbits were randomly divided into four groups:the control group, model group, safflower yellowtest group (10.9, 5.45 and 2.725 mg/kg) and the positive control (atorvastatin) group. The control group was fed with normal feed, while the other three groups were fed with high fat diet for 8 weeks, combined with intraperitoneal injection of vitamin D3, to establish hyperlipidemia model. Then, the three-dosage safflower yellow-test groups were given intraperitoneal injection of safflower yellow (10.9, 5.45 and 2.725 mg/kg), respectively, the positive control group was given atorvastatin calcium[2 mg/ (kg·d) ]by intragastric administration, and the control and model groups were orally given an equal volume of normal saline, all once a day every day for 8weeks. After 16 h fasting following the last administration, the body weight, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), oxidized low density lipoprotein (OX-LDL), matrix metalloproteinases 9 (MMP-9), tissue inhibitors of metalloproteinase 1 (TIMP-1), apolipoprotein E (ApoE), low density lipoprotein receptor (LDL-R), and scavenger receptor class B type1 (SR-B1) levels were measured. The morphological changes of thoracic aortas were examined by HE staining. Results At the 16 th week, compared with the control group, the body weight as well as the TC, TG, LDL-C, OX-LDL, MMP-9, HIF-1α, VEGF, VCAM-1 and PF4 level were all increased significantly (P＜0.05), while the level of HDL-C, ApoE, LDL-R, and SR-B1 decreased significantly (P＜0.05), accompanied with the atherosclerotic changes in the thoracic aortas indicated by the HE staining in the model group. Compared with the model group, the body weight as well as the TC, LDL-C, OX-LDL, MMP-9, HIF-1α, VEGF, VCAM-1 and PF4 level were decreased significantly (P＜0.05), and the TIMP-1 level increased (P＜0.05) in all of the three-dosage safflower yellow-test groups. Meanwhile, compared with the model group, in the 10.9 and 5.45 mg/kg safflower yellow groups, the TG level were decreased and the ApoE and SR-B1 levels were increased significantly (P＜0.05). On the other hand, the LDL-R level significantly increased only in the safflower yellow 10.9 mg/kg group (P＜0.05). HE staining showed a significant reduction in atherosclerorotic changes of the thoracic aorta in the safflower yellow-test groups. Conclusion Safflower yellow may inhibit the progression of atherosclerosis by regulating the lipid metabolism and MMP-9/TIMP-1 balance and also by inhibiting the HIF-1α, VEGF, VCAM-1 and PF4 expression.