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[中药冠心康对载脂蛋白E基因敲除动脉粥样硬化小鼠脂质代谢及血清C反应蛋白、淀粉样蛋白A和纤维蛋白原的影响]

[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].

作者信息

Mao Mei-Jiao, Hu Jun-Ping, Chen Fu-Rong, Zhang Yi-Yi, Liu Ping

机构信息

Science and Technology Agency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

出版信息

Zhong Xi Yi Jie He Xue Bao. 2011 Mar;9(3):306-12. doi: 10.3736/jcim20110312.

Abstract

OBJECTIVE

To observe the effects of Guanxinkang (GXK) decoction, a compound traditional Chinese herbal medicine, on serum lipids and apolipoprotein A I (ApoA I), apolipoprotein B (ApoB), apolipoprotein E (ApoE), C-reactive protein (CRP), serum amyloid A protein (SAA) and fibrinogen (Fbg) concentrations of ApoE-knockout mice with atherosclerosis, and to explore the mechanism of GXK decoction in anti-atherosclerosis.

METHODS

Seventy 6-week-old ApoE-knockout mice receiving a high-cholesterol diet were used to induce atherosclerosis and were randomly divided into 5 groups: untreated group, simvastatin group and low- (drug concentration is 0.864 g/mL), medium- (1.728 g/mL), and high-dose (3.456 g/mL) GXK groups. Another fourteen 6-week-old C57BL/6J mice were used as the normal control. Two 12-week-old mice were randomly selected from the normal control and the ApoE-knockout mice respectively to observe vulnerable plaque in the mouse's aortic by hematoxylin-eosin staining. Blood was collected from venous plexus of eye socket after gavage of corresponding drugs once daily for 8 weeks continuously, and then the serum was separated. Triglyceride (TAG) and total cholesterol (TC) were measured by enzyme-coupled assay; low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by selective precipitation method. Serum levels of ApoA I and ApoB were determined by turbidimetry. Double-antibody sandwich enzyme-linked immunosorbent assay was used to detect ApoE, CRP, SAA and Fbg concentrations in serum.

RESULTS

Compared with the normal control group, the levels of serum TC, TAG, LDL-C, ApoB, CRP, SAA and Fbg in the untreated group were increased (P<0.05), and the serum concentrations of HDL-C, ApoA I and ApoE in the untreated group were decreased (P<0.05). After treatment, GXK decoction and simvastatin improved the dyslipidemia by increasing the concentrations of ApoA I and HDL-C and decreasing the concentrations of TC, TAG, LDL-C, ApoB, CRP, SAA and Fbg (P<0.05). The high-dose GXK decoction had the most marked effects on SAA and Fbg and the serum lipids compared with the low-dose and medium-dose GXK and simvastatin.

CONCLUSION

GXK decoction may not only provide an active effect on hyperlipidemia, but also down-regulate the levels of serum CRP, SAA and Fbg. GXK decoction exerts an anti-atherosclerosis effect in ApoE-knockout mice.

摘要

目的

观察复方中药冠心康(GXK)水煎剂对动脉粥样硬化ApoE基因敲除小鼠血脂及载脂蛋白A I(ApoA I)、载脂蛋白B(ApoB)、载脂蛋白E(ApoE)、C反应蛋白(CRP)、血清淀粉样蛋白A(SAA)和纤维蛋白原(Fbg)浓度的影响,探讨GXK水煎剂抗动脉粥样硬化的作用机制。

方法

选取70只6周龄高脂饮食喂养的ApoE基因敲除小鼠,诱导动脉粥样硬化形成,随机分为5组:未处理组、辛伐他汀组、低剂量(药物浓度为0.864 g/mL)GXK组、中剂量(1.728 g/mL)GXK组和高剂量(3.456 g/mL)GXK组。另选取14只6周龄C57BL/6J小鼠作为正常对照组。分别从正常对照组和ApoE基因敲除小鼠中随机选取2只12周龄小鼠,通过苏木精-伊红染色观察小鼠主动脉易损斑块。连续8周每日经口灌胃相应药物后,从眼眶静脉丛取血,分离血清。采用酶联免疫吸附法测定甘油三酯(TAG)和总胆固醇(TC);采用选择性沉淀法测定低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)。采用比浊法测定血清ApoA I和ApoB水平。采用双抗体夹心酶联免疫吸附法检测血清中ApoE、CRP、SAA和Fbg浓度。

结果

与正常对照组相比,未处理组血清TC、TAG、LDL-C、ApoB、CRP、SAA和Fbg水平升高(P<0.05),血清HDL-C、ApoA I和ApoE浓度降低(P<0.05)。治疗后,GXK水煎剂和辛伐他汀通过升高ApoA I和HDL-C浓度、降低TC、TAG、LDL-C、ApoB、CRP、SAA和Fbg浓度改善血脂异常(P<0.05)。与低剂量和中剂量GXK及辛伐他汀相比,高剂量GXK水煎剂对SAA和Fbg及血脂的影响最为显著。

结论

GXK水煎剂不仅对高脂血症有积极作用,还可下调血清CRP、SAA和Fbg水平。GXK水煎剂对ApoE基因敲除小鼠具有抗动脉粥样硬化作用。

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