Dose-effect relationship between the expression of aortic vascular cell adhesion molecule-1 mRNA and qi-benefiting and blood-activating intervention on atherosclerosis / 中国组织工程研究

ABSTRACT

BACKGROUND: In traditional Chinese medicine, both deficiency as primary and excess as secondary and deficiency of qi and blood stasis are common symptoms in dialectical logy of atherosclerosis (AS). Therefore, qi-benefiting drugs are the main component of qi-benefiting and blood-activating intervention. However, the best dose relationship between qi-benefiting and blood-activating drugs needs to be further studied.OBJECTIVE: To observe the effect of qi-benefiting and blood-activating intervention on the expression of aortic vascular cell adhesion molecule-1mRNA (VCAM-1mRNA) in AS models and analyze dose-effect relationship between astragalus and sanchi.DESIGN: Randomized control animal study.SETTING: Shanxi Medical University.MATERIALS: The experiment was carried out in the Shanxi Medical University in April 2005. A total of 60 healthy male Wistar rats were selected in this study. The main reagents were quercetin (Shaanxi Huike Plant Co., Ltd., batch number:20041112), saponins of panax notoginseng (PNS, Kunming Yagechen Pharmaceutical Co., Ltd., batch number:20050118) and ligustrazine (Yuxin Guoji Longyuan Pharmaceutical Co., Ltd., batch number: 20041204).METHODS: Model establishment: Wistar rats were administrated AS feeds (including 10% yolk powder, 5% lard, 0.5% bile salt and 85% basic feed) for 3 months. Grouping and administration: At threedays after suitability feeding, 8 rats were randomly selected, regarded as the normal control group and given general feeds, and other 52 rats were fed with AS feeds. Three months later, 4 rats were randomly selected for the measurements of lipid and aortic tissue. And then, the models were established successfully. In addition, 48 rats were randomly divided into 6 groups. ① Astragalus treatment group: Rats were perfused with 0.1 g/(kg·d) quercetin. ② Sanchi treatment group: Rats were perfused with 0.1 g/(kg·d)PNS. ③ 2∶1 of astragalus/sanchi treatment group: Rats were perfused with 0.1 g/(kg·d) quercetin and 0.05 g/(kg·d) PNS.④ 3∶1 of astragalus/sanchi treatment group: Rats were perfused with 0.15 g/(kg·d) quercetin and 0.05 g/(kg·d) PNS. ⑤Ligustrazine treatment group: Rats were perfused with 0.2 g/(kg ·d) ligustrazine (Yuxin Guoji Longyuan Pharmaceutical Co., Ltd.). ⑥ Normal control group: Rats were fed with general feeds. ⑦ Model group: Rats were fed with general feeds after successful model estalishement. Thirty days after administration, relative expression of VCAM-1mRNA inaorta was measured with reverse transcription polymerase chain reaction (RT-PCR) technique; moreover, 2 mL venous blood was collected from tail to measure the levels of serum total cholesterol (TC), triacylglycerol (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C).MAIN OUTCOME MEASURES: ① Relative expression of VCAM-1mRNA in aorta; ② level of lipid.RESULTS: Among 60 male Wistar rats, three rats in the treatment group died because of perfusion and two rats in the model group died due to accident; therefore, a total of 51 rats were involved in the final analysis. ① High-lipid diet could promote the formation of AS models. Level of lipid was higher in the model group than that in the normal control group (P＜ 0.05), and leves of serum TC, TG and LDL-C were lower in the interventions group than those in the model group (P ＜0.05). ② Expression of VCAM-1mRNA was not found in the normal control group. Expression of VCAM-1mRNA was lower in the intervention groups than that in the model group. Expression of VCAM-1mRNA (0.42±0.02) was the lowest in 3∶1 of astragalus/sanchi treatment group, and there were significant differences as compared with other intervention groups (P ＜ 0.05).CONCLUSION: Astragalus and sanchi, a main component of qi-benefiting and blood-activating herbs, can down-regulate the level of lipid and resist AS; meanwhile, the combination of them is superior to the single application; in addition, with the increasing deal of qi-benefiting drugs, the function against AS is strengthened.