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目的探讨鸢尾苷元(tectorigenin)在动脉粥样硬化(AS)模型兔体内的血药浓度与给药剂量和降脂疗效的相关性。方法48只健康雄性日本大耳白兔随机分为6组。正常对照组给予普通饲料、模型组及各给药组均给予高脂饲料喂养。鸢尾苷元高、中、低剂量组分别给予鸢尾苷元50、25、12.5 mg·kg~(-1)·d~(-1),阳性对照组给予阿托伐他汀5 mg·kg~(-1)·d~(-1)。给药第8周采血,高效液相色谱法检测鸢尾苷元血药浓度。连续给药12周,全自动生化分析仪检测血脂;分离胸腹主动脉段,大体观察血管内膜斑块形成情况;剪取主动脉弓下缘血管段行病理检查。结果鸢尾苷元的平均稳态血药浓度随着给药剂量的增加而增加,具有显著的相关性(r=0.969 1),但并非等比例增加。鸢尾苷元高、中、低剂量组均可显著降低AS模型兔血清总胆固醇、低密度脂蛋白胆固醇和甘油三酯水平,并升高高密度脂蛋白胆固醇,抑制血管内膜增生,但作用强度不如阿托伐他汀组。结论鸢尾苷元在AS模型兔体内的血药浓度与给药剂量相关,具有明显降脂和抗AS作用。
Objective To investigate the relationship between the plasma concentration of tectorigenin and the dose of lipid and lipid-lowering efficacy in atherosclerosis (AS) model rabbits. Methods Forty-eight healthy male Japanese white rabbits were randomly divided into 6 groups. The normal control group was given normal diet, the model group and each administration group were given high-fat feed. The tectorigenin of high, middle and low doses of tectorigenin were given 50, 25 and 12.5 mg · kg -1 · d -1 of tectorigenin, respectively. The positive control group was given atorvastatin 5 mg · kg ~ (-1) -1) · d ~ (-1). Blood was collected on the 8th week of administration, and the plasma concentration of tectorigenin was detected by high performance liquid chromatography. Continuous administration for 12 weeks, automatic biochemical analyzer for detecting blood lipids; isolated aorta thoracic and abdominal aortic, general observation of the formation of intimal blood vessels; cut the lower edge of the aortic arch vascular pathological examination. Results The average steady-state plasma concentration of tectorigenin increased with the increase of the dosage, with a significant correlation (r = 0.969 1), but not an isometric increase. The tectorigenin of high, medium and low dose groups could significantly reduce the levels of serum total cholesterol, low density lipoprotein cholesterol and triglyceride in AS model rabbits and increase high density lipoprotein cholesterol and inhibit the intimal hyperplasia, but the effect intensity As atorvastatin group. Conclusion The concentration of tectorigenin in AS model rabbits is related to the dose of administration, which has the effect of decreasing lipid and anti-AS.