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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

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*△▲
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