中药复方制剂干预动脉粥样硬化的实验研究

doi:10.16138/j.1673-6087.2021.04.008

摘要/Abstract

摘要：

目的：探究以白藜芦醇、小檗碱、姜黄素和青蒿琥酯单体组合为基础,以合理的剂量配比达到对动脉粥样硬化干预最有效和安全的复方制剂,以期对他汀不耐受患者提供一种干预动脉粥样硬化的方案。方法：通过高脂饲料法建立载脂蛋白E敲除（apolipoprotein E-knockout,ApoE^-/-）小鼠动脉粥样硬化模型。选择白藜芦醇、小檗碱、姜黄素、青蒿琥酯4种中药单体各分3种剂量梯度,按照正交试验表L₉（3⁴）分为9组中药复方制剂。通过评估各组小鼠动脉粥样硬化程度、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol,LDL-C）,进而得出上述4种药物在剂量配比上最有效及最安全的配比剂量,并进行验证,确定正交试验的结果。结果：正交试验极差分析提示LDL-C水平、主动脉粥样硬化斑块等指标的相应最佳配方为白藜芦醇1.25 mg/(kg·d)、小檗碱0.625 mg/(kg·d)、姜黄素12.5 mg/(kg·d)、青蒿琥酯6.25 mg/(kg·d)。中药复方制剂组较单药组的动脉粥样斑块面积小,谷丙转氨酶低（均P<0.05）。结论：通过正交试验分析初步推断出防治动脉粥样硬化的最佳配伍组方,并对其有效性、安全性进行验证,为中医药在干预动脉粥样硬化的临床转化方面提供研究依据。

关键词: 动脉粥样硬化, 白藜芦醇, 小檗碱, 姜黄素, 青蒿琥酯, 正交试验

Abstract:

Objective To explore a combination of resveratrol, berberine, curcumin and artesunate with a reasonable dose ratio to obtain the most effective and safest compound combination to provide an alternative selection for the patients with atherosclerosis and statin intolerance. Methods The atherosclerotic model in apolipoprotein E-knockout (ApoE^-/-) mice was established by high fat diet. Four compound of Chinese medicine including resveratrol, berberine, curcumin and artesunate were divided into 9 groups according to orthogonal test table L₉(3⁴). Through evaluating the degree of atherosclerosis and the level of low-density lipoprotein cholesterol（LDL-C） in each group, the most effective and safest combination of 4 compounds were obtained and verified. Results According to the therapeutic effect on blood LDL-C and aortic atherosclerotic plaque, the range analysis of orthogonal experiment suggested the best compound combination, which was: resveratrol 1.25 mg/(kg·d), berberine 0.625 mg/(kg·d), curcumin 12.5 mg/(kg·d), artesunate 6.25 mg/(kg·d). In verification phase, it was shown that the traditional Chinese medicine combination group had smaller atherosclerotic plaque areas, lower liver injury than the single drug group (all P<0.05). Conclusions Through orthogonal test, we obtained a best compound combination of traditional Chinese medicine in all combination groups, which could prevent atherosclerosis and was verified to be effective and safe. This study provided a reference method in clinical transformation for traditional Chinese medicine.

Key words: Atherosclerosis, Resveratrol, Berberine, Curcumin, Artesunate, Orthogonal experiment

中图分类号:

R543

王顺, 朱华芳, 毛承誉, 李东九, 王长谦. 中药复方制剂干预动脉粥样硬化的实验研究[J]. 内科理论与实践, 2021, 16(04): 261-266.

WANG Shun, ZHU Huafang, MAO Chengyu, LI Dongjiu, WANG Changqian. Experimental study of the effect of compound combination of traditional Chinese medicine on atherosclerosis[J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(04): 261-266.

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项目	白藜芦醇组	小檗碱组	姜黄素组	青蒿琥酯组	中药复合物组	阿托伐他汀钙组	高脂饲料组	F	P
斑块面积占比(%)	16.97±0.06¹⁾	15.41±1.18¹⁾	15.59±0.72¹⁾	15.28±0.87¹⁾	10.75±0.93	9.53±1.26	25.96±2.25¹⁾	88.827	<0.001
ALT(U/L)	34.68±6.82	36.52±6.39	37.58±6.38	39.44±3.84	36.40±7.01	57.56±5.64²⁾	42.89±5.33	8.623	<0.001
Cr（μmol/L）	38.60±6.19	42.60±8.02	43.00±5.92	42.80±4.76	40.60±7.57	41.20±5.07	41.20±8.47	0.269	0.947