Mao Mei-jiao, Hu Jun-ping, Wang Cong, Zhang Yi-yi, Liu Ping
Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Zhong Xi Yi Jie He Xue Bao. 2012 Jul;10(7):814-20. doi: 10.3736/jcim20120713.
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.
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.
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.
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.
观察复方中药冠心康（GXK）水煎剂对动脉粥样硬化载脂蛋白E（ApoE）基因敲除小鼠过氧化物酶体增殖物激活受体γ（PPARγ）、肝X受体α（LXRα）和ATP结合盒转运蛋白A1（ABCA1）表达的影响。
选取14只6周龄C57BL/6 J小鼠作为正常对照组。将70只6周龄给予高胆固醇饮食诱导动脉粥样硬化的ApoE基因敲除小鼠随机分为未治疗组、辛伐他汀组以及低剂量（生药浓度为0.864 g/mL）、中剂量（生药浓度为1.728 g/mL）和高剂量（生药浓度为3.456 g/mL）GXK组。连续用药8周后，分离小鼠的肝脏和主动脉。分别采用实时定量聚合酶链反应和蛋白质免疫印迹法检测PPARγ、LXRα和ABCA1的表达。
与正常对照组相比，未治疗组PPARγ、LXRα和ABCA1的mRNA和蛋白表达上调（P<0.05）。治疗后，GXK水煎剂和辛伐他汀降低了PPARγ、LXRα和ABCA1的表达（P<0.05）。高剂量GXK水煎剂的作用比低、中剂量GXK及辛伐他汀更显著。
PPARγ-LXRα-ABCA1通路参与脂质调节和炎症活动。这些基因的过表达对高胆固醇饮食的ApoE基因敲除小鼠的动脉粥样硬化有复杂影响。GXK水煎剂通过调节ApoE基因敲除小鼠中PPARγ、LXRα和ABCA1的相互作用而具有抗炎和抗基质金属蛋白酶活性。
