The Main Effect Of Guanxin No.2 Formula And Its Components On The Gene Expression Of The Myocardial Infarction Rats

Cardiac infarction is one of the main causes of death in both developing and developed countries over past decades.Currently available approaches for treating patients with this disease are not satisfied.Traditional Chinese medicines(TCMs) have been increasingly paid attention to.Guanxin No.2 decoction(GXâ…¡)is a well researched decoction,and is widely used to treat with the cornary artery disease (CAD)patients in China and other Asian countries clinically.But the pathogenesis of CAD is still blurry,and the mechanism of the decoction is also not clear.The main purpose of this research is to detect the time related changes of the expression of cardiac genes,the mechanism of the protection of GXâ…¡on the disease,and the effect of the single component of GXâ…¡.A rat cardiovascular related oligonucleotide microarray was constructed.The genes waere selected from the literatures in which they were reported as candidate genes, and business cardiovascular microarrays,and some related databases.Furthermore, the most important part of this gene set was a number of heart specific genes which was detected by chi-square test from the UniGene database.The microarray has been tested by self-self RNA hybridization.Data shows the correlation was satisfied,so our microarray suited for the research.The microarray was used to examine the gene expression pattern of the rat myocardial infarction(MI)model,which was carried out by ligating the proximal left anterior descending coronary artery.More differentially expressed(DE)genes were found after 3 days of the ligation,and the DE genes were clustered together in shorter time points,i.e.1 day,3 days,and 7 days after the experiment,and they were more different from day 15,and day 30.Former pharmacological experiments showed a plaque was formed after the ligation and expanded to a larger part with time goes by, so the genes which participated in the plaque forming and the genes which expressed after the plaque formed were quite different.The DE genes that expressed all through the time have been researched.Among these genes,a number of them which participated in the PPAR signaling pathway were inhibited,and genes which participated in fatty acid metabolism were significantly down regulated at the 1^stday after the ligation.So during the myocardial infarction,the fatty acid metabolism was significantly inhibited.The analysis of heart specific genes in the MI model revealed that at the 30^thday after infarction,most of the genes were down regulated,which implicated that the function of the heart was extremely destroyed.This was similar to the pharmacological results we carried out earlier.After the administration of GXâ…¡and its components,most of the cardiac genes showed an opposite expression compared to the models,which implied the protection effects of the decoction and its components.According to our classification of the genes,their early changes were response to the medicine,and in the process of time,more and more genes have been regulated to their normal level,but at the 30^thday after infarction,the genes were regulated solely by the medicine again.We then classified the phases of the administration of decoction to three parts:the early phase was the therapeutic time,and the next was the recovery phase,and the consolidated phase.The gene expression of the GXâ…¡group was similar to the Xue group at the 1^stday and the 7^thday,but it was closer to Jiangxiang,which belonged to Qi group according to the classification of Chinese traditional doctors.So we inferred that during the plaque formation phase,the Xue group of the decoction revealed a strong therapeutic effect.But after the formation, the Qi group showed a regulated effect.The decoction and its components could regulate the expression of Cx32 to a normal expression,which implied that the mechanisms of the proliferation effect of the decoction may be regulating the expression of Cx32 and then inhibiting the elongation of the cell cycle,and increase the proliferation.Formerly pharmacological experiments showed the GXâ…¡had an effect of angiogenesis,but the known genes in which participated the process,such as VEGF and FGF,were not increased in our dataset.This implies that the angiogenesis initiated by GXâ…¡and its components might not be induced by the up regulation of VEGF and FGF,other mechanisms should be considered.