Tiaozhi Tongmai Granules reduce atherogenesis and promote the expression of ATP-binding cassette transporter A1 in rabbit atherosclerotic plaque macrophages and the liver
- Author:
Sun QING
1
;
Zhang LU
;
Guo SHUWEN
;
Zheng MIN
;
Yang DANDAN
;
Zheng CHENGLONG
;
Wu JIANI
;
Liu JIAN
;
Wu JINGPING
Author Information
1. Department of Biochemistry
- Keywords:
Atherosclerosis;
ABCA1;
Chinese medicine;
Macrophages;
Liver
- From:
Journal of Traditional Chinese Medical Sciences
2014;1(1):38-48
- CountryChina
- Language:Chinese
-
Abstract:
Objective:ATP-binding cassette transporter A1 (ABCA1) is an integral membrane protein that plays a key role in cellular lipid metabolism,preventing the accumulation of lipids that contribute to the initiation and progression of atherosclerosis.Tiaozhi Tongmai Granules are a Chinese herbal compound that is capable of treating atherosclerosis.This study was de-signed to explore the potential pharmacological mechanism by which Tiaozhi Tongmai Gran-ules protect against atherosclerosis.Methods:Forty-nine male New Zealand rabbits were randomly divided into seven groups:normal control group,normal diet;model groups 1 and 2:balloon injury and high-fat diet for 6 or 12 weeks;statin groups 1 and 2:balloon injury and high-fat diet plus atorvastatin for 6 or 12 weeks;and Chinese herb groups 1 and 2:balloon injury and high-fat diet plus Tiaozhi Tongmai Granules for 6 or12 weeks.The granules were administered at a dose of 1.14 g/kg/d,with atorvastatin(1.14 mg/kg/d) serving as positive control.Serum lipid profiles and liver function indices were measured.Atherogenesis was viewed after H&rE staining and quantified by thickened intimal area percentage and maximal intimal thickness percentage.The ABCA1 protein expression in athero-sclerotic plaque macrophages of the common carotid arteries (CCA),thoracic aortae (TA),and liver tissues were observed by immunohistochemical staining and evaluated using mean optical density (OD) value in macrophages and ABCA1-positive hepatocyte number.Results:Compared with model group 1 at week 6,Chinese herb group 1 and statin group 1 dis-played significant reductions in total cholesterol (TC) (P =0.027,0.012) and low-density lipopro-tein cholesterol (LDL-C) (P =0.039,0.028) levels,as well as marked increases in ABCA1-positive hepatocyte numbers (Pall ＜0.001),and only statin group 1 displayed a markedly reduced maximal intimal thickness percentage in the CCA (P =0.018).Compared with model group 2 at week 12,Chinese herb group 2 and statin group 2 all presented significant reductions in TC (P =0.011,0.003),LDL-C (P =0.017,0.010) and thickened intimal area percentage in the CCA (P =0.001,0.022),as well as prominent increases in the ABCA1OD value of both the CCA (P =0.001,0.039) and TA (P =0.001,0.025) and positive hepatocyte number (P all ＜0.001).Chinese herb group 2 had a markedly reduced maximal intimal thickness percentage compared with model group 2 (P =0.006) and a higher positive hepatocytes number than statin group 2 (P =0.001).Conclusions:Tiaozhi Tongmai Granules appear to have an anti-atherogenic effect that is most likely mediated by simultaneously upregulating the protein expression of ABCA1 in rabbit athero-sclerotic plaque macrophages and in the liver.
