ABSTRACT
Objective:To investigate the mechanism of Shugan Wendan decoction in treating atherosclerosis based on liver X receptor α(LXRα)/nuclear factor-κB(NF-κB) signal. Method:A New Zealand rabbit model of atherosclerosis with liver-Qi stagnation was established by using calf serum albumin immune injury, high fat feeding and bondage emotional stress method. Theses rabbits are randomly divided into 6 groups, control group,model group, atorvastatin group, Shugan Wendan decoction low, medium and high dose group(2.18,6.54,19.62 g·kg-1·d-1). After successful modeling, the rabbits were treated by injecting drugs with Atorvastatin and low, middle and high dose Shugan Wendan decoction to gastric.The control group and the model group were given intragastric administration of saline in the same volume. The period of gavage is 6 weeks. The pathological changes of the rabbits were detected by hematoxylin-eosin(HE) staining.Serum levels of totalcholesterol(TC), triglyceride(TG),low density extremityprotein(LDL-C), high density extremity protein(HDL-C), nitric oxide(NO), and endothelin-1(ET-1) of the rabbits were detected by enzyme method, nitrate reductase method, and enzyme-linked immunosorbent assay(ELISA), respectively.The gene expression of CRP, IL-1β, IL-6 and MMP-9 in the aorta was detected by Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) method.The protein expression of LXRα/NF-κB signaling pathway wasdetected by Western blot. Result:Compared with normal control group, in model group, the lumen of the blood vessels was significantly narrowed, atheromatous plaques were formed, and a large number of intracellular foam-like changes were seen. In atorvastatin group and Shugan Wendan decoction group, the blood vessels in high, middle, and low concentration groups were narrowed. Atherosclerotic plaques and foam-like changes were all lower than the model group.Compared with the normal control group, the TG, TC, and LDL-C levels in the model groupincreased(PPPPβ, IL-6 and MMP-9 all increased(Pα protein in the model group was decreased(PκB was increased(PPPβ, IL-6 and MMP-9 in the atorvastatin group,the low, middle and high dose Shugan Wendan decoction groups all decreased(Pα protein in the group was increased(PκB was decreased(PConclusion:Shugan Wendan decoction can inhance the function of vascular endothelial cells and the stability of atherosclerotic plaque by regulating LXRα/NF-κB signaling pathway.
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.