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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (7): 814-820.doi: 10.3736/jcim20120713

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Guanxinkang on expression of PPARγ-LXRα-ABCA1 pathway in ApoE-knockout mice with atherosclerosis

Mei-jiao Mao1, Jun-ping Hu1, Cong Wang2, Yi-yi Zhang1, Ping Liu1()   

  1. 1. Science and Technology Agency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2. Celluar Biology Laboratory, Seientific Research Center, Shanghai Public Health Clinical Center, Shanghai 201508, China
  • Received:2011-10-24 Accepted:2011-11-28 Online:2012-07-20 Published:2018-07-15
  • Contact: Ping Liu E-mail:liuping23@sina.com

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Objective: To observe the effects of Guanxinkang (GXK) decoction, a compound traditional Chinese herbal medicine, on expressions of peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα) and ATP-binding cassette transporter A1 (ABCA1) in apolipoprotein E (ApoE)-knockout mice with atherosclerosis.
Methods: Fourteen 6-week-old C57BL/6 J mice were used as normal control group. Seventy 6-week-old ApoE-knockout mice receiving a high-cholesterol diet to induce atherosclerosis were randomly divided into untreated group, simvastatin group and low-dose (concentration of crude drugs at 0.864 g/mL), medium-dose (crude drugs at 1.728 g/mL) and high-dose (crude drugs at 3.456 g/mL) GXK groups. After treated with the drugs for eight weeks continuously, the livers and aortas of mice were separated. The expressions of PPARγ, LXRα and ABCA1 were measured by real-time quantitative polymerase chain reaction and Western blotting respectively.
Results: Compared with the normal control group, mRNAs and proteins of PPARγ, LXRα and ABCA1 over-expressed in the untreated group (P<0.05). After the treatment, GXK decoction and simvastatin decreased the expressions of PPARγ, LXRα and ABCA1 (P<0.05). High-dose GXK decoction had more marked effects than low- and medium-dose GXK and simvastatin.
Conclusion: The PPARγ-LXRα-ABCA1 pathway is involved in lipid regulation and inflammation activities. Over-expression of the genes has complicated effects on atherosclerosis in ApoE-knockout mice with high-cholesterol diet. GXK decoction has anti-inflammatory and anti-matrix metalloproteinase activities by regulating PPARγ, LXRα and ABCA1 interactions in the ApoE-knockout mice.

Key words: drugs, Chinese herbal, atherosclerosis, apolipoprotein E, ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor γ, liver X receptor α, mice

Table 1

Reactive system of real-time fluorescent quantization PCR"

Content Volume (μL)
2×Toyobo Premix EX Taq 12.5
FCD 1
ddH2O 8.8
Primers 0.7
Template 2

Table 2

Relative expression levels of PPARγ, LXRα and ABCA1 mRNAs in livers of ApoE-knockout mice (x±s)"

Group n PPARγ mRNA LXRα mRNA ABCA1 mRNA
Normal control 8 1.02±0.18 1.02±0.16 1.05±0.32
Untreated 8 8.54±0.82** 3.63±1.35** 4.95±0.63**
Simvastatin 8 6.54±1.59*△ 1.89±0.69*△ 3.77±0.95*△
Low-dose GXK 8 8.19±1.83*▲▲□□■■ 3.14±0.68*▲▲□□■■ 4.82±1.27*▲▲□□■■
Medium-dose GXK 8 6.08±1.56*△ 1.98±0.38*△ 3.59±0.44*△
High-dose GXK 8 2.25±0.92△▲▲□□ 1.51±0.64△ 1.66±0.34△▲▲□□

Table 3

Relative expression levels of PPARγ, LXRα and ABCA1 mRNAs in aortas of ApoE-knockout mice (x±s)"

Group n PPARγ mRNA LXRα mRNA ABCA1 mRNA
Normal control 8 1.04±0.34 1.01±0.16 1.03±0.30
Untreated 8 7.88±1.21** 2.14±0.51** 4.50±1.00**
Simvastatin 8 6.07±1.65*△△ 1.36±0.38△△ 2.77±0.59*△△
Low-dose GXK 8 7.34±0.69*▲□■ 1.80±0.37*▲□■ 4.26±1.22*▲▲□■
Medium-dose GXK 8 5.68±0.71*△△ 1.43±0.31*△△ 2.65±0.80*△△
High-dose GXK 8 2.48±0.42*△△▲▲□□ 0.98±0.28△△▲□ 1.26±0.16△△▲▲□□

Figure 1

Expressions of PPARγ, LXRα and ABCA1 proteins in livers (A) and aortas (B) of ApoE-knockout mice H: High-dose GXK group; M: Medium-dose GXK group; L: Low-dose GXK group; N: Normal control group; C: Untreated group; S: Simvastatin group. PPARγ: peroxisome proliferator-activated receptor γ; LXRα: liver X receptor α; ABCA1: ATP-binding cassette transporter A1; GXK: Guanxinkang; GAPDH: glyceraldehyde-3-phosphate dehydrogenate."

Table 4

Relative expression levels of PPARγ、LXRα、ABCA1 proteins in livers of ApoE-knockout mice (x±s)"

Group n PPARγ protein LXRα protein ABCA1 protein
Normal control 8 0.33±0.05 0.38±0.06 1.49±0.08
Untreated 8 1.64±0.06* 1.37±0.32* 2.22±0.02*
Simvastatin 8 0.61±0.06*△ 1.10±0.06*△ 1.90±0.07*△
Low-dose GXK 8 1.01±0.03*△▲□■ 1.02±0.10*△□■ 1.21±0.25*△▲□■
Medium-dose GXK 8 0.49±0.01*△▲ 0.58±0.12△▲ 0.77±0.18*△▲
High-dose GXK 8 0.51±0.01*△▲ 0.76±0.22*△▲ 0.34±0.13*△▲□

Table 5

Relative expression levels of PPARγ, LXRα and ABCA1 proteins in aortas of ApoE-knockout mice (x±s)"

Group n PPARγ protein LXRα protein ABCA1 protein
Normal control 8 0.36±0.04 0.19±0.02 1.66±0.04
Untreated 8 2.99±0.24* 2.18±0.32* 2.62±0.22*
Simvastatin 8 1.25±0.19*△ 1.69±0.05*△ 1.06±0.15*△
Low-dose GXK 8 1.23±0.05*△□■ 1.38±0.07*△□■ 1.18±0.04*△□■
Medium-dose GXK 8 0.88±0.06*△▲ 1.16±0.23*△▲ 0.33±0.04*△▲
High-dose GXK 8 0.67±0.08*△▲ 0.80±0.19*△▲□ 0.15±0.01*△▲
[1] Soumian S, Albrecht C, Davies AH, Gibbs RG . ABCA1 and atherosclerosis[J]. Vasc Med, 2005,10(2):109-119
doi: 10.1191/1358863x05vm593ra
[2] Mao MJ, Hu JP, Chen FR, Zhang YY, Liu P . Effects of Chinese herbal medicine Guanxinkang on lipid metabolism and serum C-reactive protein, amyloid A protein, and fibrinogen in apolipoprotein E-knockout mice with atherosclerosis[J]. J Chin Integr Med, 2011,9(3):306-312
毛美娇, 胡俊萍, 陈富荣, 章怡祎, 刘萍 . 冠心康对载脂蛋白E基因敲除动脉粥样硬化小鼠血脂及炎性标志物的影响[J]. 中西医结合学报, 2011,9(3):306-312
[3] Hanriot D, Bello G, Ropars A, Seguin-Devaux C, Poitevin G, Grosjean S, Latger-Cannard V, Devaux Y, Zannad F, Regnault V, Lacolley P, Mertes PM, Hess K, Longrois D . C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor alpha, on human monocytes[J]. Thromb Haemost, 2008,99(3):558-569
doi: 10.1160/TH07-06-0410
[4] Filep JG . Perplexity of monocyte responses to C-reactive protein(CRP)[J]. Thromb Haemost, 2008,99(3):461-462
doi: 10.1160/TH08-02-0072 pmid: 18327390
[5] Lawn RM, Wade DP, Couse TL, Wilcox JN . Localization of human ATP-binding cassette transporter 1(ABC1) in normal and atherosclerotic tissues[J]. Arterioscler Thromb Vasc Biol, 2001,21(3):378-385
doi: 10.1161/01.ATV.21.3.378
[6] Reddy ST, Hama S, Ng C, Grijalva V, Navab M, Fogelman AM . ATP-binding cassette transporter 1 participates in LDL oxidation by artery wall cells[J]. Arterioscler Thromb Vasc Biol, 2002,22(11):1877-1883
doi: 10.1161/01.ATV.0000035700.82829.2A pmid: 12426219
[7] Joyce CW, Amar MJ, Lambert G, Vaisman BL, Paigen B, Najib-Fruchart J, Hoyt RF Jr, Neufeld ED, Remaley AT, Fredrickson DS, Brewer HB Jr, Santamarina-Fojo S . The ATP binding cassette transporter A1(ABCA1) modulates the development of aotric atherosclerosis in C57BL/6 and apoE-knockout mice[J]. Proc Natl Acad Sci U S A, 2002,99(1):407-412
doi: 10.1073/pnas.012587699
[8] Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ . Regulation of mouse sterol regulatory element-binding protein-1c gene(SREBP-1c) by oxysterol receptors, LXRα and LXRβ[J]. Genes Dev, 2000,14(22):2819-2830
doi: 10.1101/gad.844900
[9] Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R, He J, Lee JH, Khadem S, Ren S, Li S, Silverstein RL, Xie W . Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARγ in promoting steatosis[J]. Gastroenterology, 2008,134(2):556-567
doi: 10.1053/j.gastro.2007.11.037
[10] Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM . PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL[J]. Cell, 1998,93(2):241-252
doi: 10.1016/S0092-8674(00)81575-5
[11] Hu Q, Zhang Y, Zhang XJ, Feng JB, Liu CX, Jiang H, Jiang GH, Wang R . PPARγ gene and protein expression in aortic plaque of different week-old knock-out mice and relationship with the composition of aortic plaque[J]. Zhongguo Bing Li Sheng Li Za Zhi, 2006,22(12):2289-2295
doi: 1000-4718
胡琴, 张运, 张宪军, 冯进波, 刘春喜, 姜虹, 蒋桂花, 王蓉 . PPARγ在不同周龄apoE-/-小鼠主动脉斑块表达及与斑块成分的相互关系[J]. 中国病理生理杂志, 2006,22(12):2289-2295
doi: 1000-4718
[12] Zhang YY, Liu P . The effects of Guanxinkang on aortic LXRα, ABCA1 gene expression in atherosclerosis rats[J]. Zhongguo Dong Mai Ying Hua Za Zhi, 2010,18(8):614-616
章怡祎, 刘萍 . 冠心康对动脉粥样硬化大鼠主动脉LXRα、ABCA1基因表达的影响[J]. 中国动脉硬化杂志, 2010,18(8):614-616
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