参芪复方对糖尿病大血管病变KK-A~y小鼠主动脉基因表达影响的拆方研究

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目的:本研究旨在通过全基因组表达谱芯片研究参芪复方及其拆方组分中药对糖尿病大血管病变KKA~y小鼠主动脉的作用,以分析参芪复方配伍的合理性和科学性。方法:8周龄SPF级雄性自发性2型糖尿病KKA~y小鼠60只,随机分为模型组、参芪复方组、益气养阴组、活血组。予高脂饲料及添加L-NAME的纯净水连续饲养8周,建立糖尿病大血管病变模型。造模后分别予生理盐水、参芪复方全方、益气养阴组分和活血组分中药对各组进行灌胃干预,疗程8周。干预后第8周末处死全部动物,取腹主动脉做HE染色及全表达谱芯片。结果:第8周末,参芪复方组动物主动脉病理损伤较模型组明显减轻,益气养阴组和活血组动物组织病变程度较模型组轻,但较参芪复方组为重。差异基因分析显示,参芪复方可能通过调节膜偶联蛋白在膜泡运输中的相互作用、不饱和脂肪酸的合成、MAPK信号通路和花生四烯酸的代谢等信号通路,调节了糖脂代谢、细胞凋亡、分化、增殖及炎症反应,从而改善糖尿病大血管病变,对整体的调节作用优于益气养阴组及活血组作用之和。结论:参芪复方对糖尿病大血管病变KKA~y小鼠主动脉的基因表达有着广泛的正面调节作用,其疗效依靠药物之间的合理配伍、协同增效,共同达到改善糖尿病大血管病变的作用。 Objective: The purpose of this study is to investigate the effect of Shenqi Compound and its components in traditional Chinese medicine on the aorta of KKA-y mice with diabetic macroangiopathy by genome-wide expression microarray to analyze the rationality and scientificity of Shenqi compound compatibility . Methods: Sixty KK-y mice of 8-week-old SPF male spontaneous type 2 diabetes mellitus were randomly divided into model group, Shenqi Compound group, Yiqi Yangyin group and Huoxue group. High-fat diet and pure water with L-NAME were fed for 8 weeks continuously to establish diabetic macroangiopathy model. After the model were given saline, Shenqi Compound all, Qi and Yin components and blood components of traditional Chinese medicine for each group gavage intervention, the course of 8 weeks. At the end of the 8th week after intervention, all animals were sacrificed and the abdominal aorta was taken for HE staining and full-expression microarray. Results: At the end of the 8th week, the pathological changes of the aorta in Shenqi Compound group were significantly lessened compared with the model group. The degree of tissue lesion in Yiqi Yangyin group and Huoxue group was lighter than that in the model group, but heavier than that in Shenqi Compound group. Differential gene analysis showed that Shenqi compound regulates glucose and lipid metabolism by regulating the interaction of membrane-associated proteins in vesicular transport, the synthesis of unsaturated fatty acids, the MAPK signaling pathway and the metabolism of arachidonic acid. Apoptosis, differentiation, proliferation and inflammatory response, thereby improving diabetic macroangiopathy, the overall regulatory effect is better than the Yiqi Yangyin group and the role of activating blood group. Conclusion: Shenqi Compound has a broad positive effect on the gene expression of the aorta of KKA-y mice with diabetic macroangiopathy. The therapeutic effect depends on the rational compatibility and synergism between the drugs, which can help to improve the diabetic macroangiopathy. .
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