| Objective:To study the influence of Uncaria compatibility with Gastrodia on the distribution of its effect ingredient in rat’s macrovascular, and the effect on rat macrovascular’s gene expression before and after compatibility. To explore the difference of the effect ingredient’s distribution and the gene expression before and after the compatibility of Uncaria with Gastrodia.Methods:The methodology of the pretreatment of rats’macrovascular was Investigated, and then the method of pretreatment and the detection conditions of HPLC were determined. Using the method being determined, the content in different time of Isorhynchophylline in SHR rat’s macrovascular was setting-out before and after compatibility. And the pharmacokinetic characteristics was analyzed with3P97software. By using cDNA microarray, the macrovascular gene expression before and after compatibility was studied, to explore Uncaria hypotensive effect and the influence of the compatibility on it.Results:The results of Isorhy’s distribution in SHR rat’s macrovascular showed that Tmax of Isorhy in macrovascular was in advance to120min from150min, and Cmax increased significantly. The metabolic and elimination rate were increased after compatibility, and AUC0-240min decreased.The results of cDNA microarray worked out that, the differentially expressed genes in Uncaria-blank group were1079, the genes in Tianmagouteng-blank group were1568. the genes in Tianmagouteng-Uncaria group were428.37genes were obtained after the intersection of the three. After disjointly analyzing the all differentially expressed genes in Uncaria group and Tianmagouteng group with GO analysis and Pathway analysis,45target GO entry and22target biological pathways were gained respectively. In those GO entry and biological pathways, Vascular smooth muscle contraction and vasodilation were related most closely with Uncaria’s vasodilator and hypotensive effect, and differentially expressed genes were35by statistics. After analysis, the most of the35genes were receptor gene and enzyme gene, and their expression products were mainly the effect components in the G-protein coupled receptor signaling pathway; some genes directly or indirectiy acted on vascular smooth muscle or Ca2+channel, regulating vascular contraction and coregulating blood pressure; some other genes could regulate platelet aggregation, blood flow and inflammatory response. In addition, the related gene expression had upward or downward trend before and after Compatibility.Conclusions:The compatibility with Gastrodia has effect on Uncaria’s distribution, which prompts that Gastrodia can promote the distribution of Isorhy in SHR rat’s macrovascular, and it may states that Gastrodia can enhances Uncaria’s effect of lowering blood pressure.Uncaria make blood pressure lower mainly by affecting G-protein coupled receptor signaling pathway (AC signaling pathway, phosphatidyl inositol signaling pathway, NO signal transduction pathway). It can also improve platelet aggregation, blood flow and inflammatory response, playing the efficacy of the overall regulation of blood pressure. And that, Gastrodia, to a certain extent, can enhance Uncaria’s vasodilator, hypotensive, comprehensive treatment of hypertension, which confirms the reasonable and scientific of drug compatibility on the gene expression level.The study of Isorhy’s distribution in SHR rat’s macrovascular and the cDNA microarray both indicate that the compatibility with Gastrodia can enhances Uncaria’s effect of lowering blood pressure. And the changes of the content of effects ingredient’ distribution can be explained with the related genes’ expression, but the specific reasons need further study. |
