Calcium Transport And Protein Related Gene Expression In Rat Yiqihuoxue Drugs On Diastolic Dysfunction

Diastolic dysfunctionrefers to the impaired ventricular active relaxation, passive filling capacity or compliance fall in a set of clinical circulation dysfunction syndrome. Protein kinase phosphorylation regulating calcium transport protein is the basis of maintaining normal diastolic function of heart muscle cells, the anomaly is an important pathological mechanism of diastolic cardiac insufficiency, and may become potential targets for intervention. TCM holds that the basic pathogenesis of heart failureis Qi deficiency and blood stasis, throughout the occurrence and development of heart failure. Dangshen, Huangqi, Sanqi, Danshenare commonly used in the clinical treatment of heart failure. Prior research has shown that yiqi huoxue medicine is good for the improvement of cardiac diastolic function, which may be related to regulation, to keep the normal myocardial cell calcium transport.Diastolic cardiac insufficiency include active diastolic dysfunction and passive stretching obstacles, and calcium transport protein kinase signal regulating circuit is to maintain the important pathophysiological link of cardiac diastolic function actively. Myocardial cells excited-contraction coupling process, sarcoplasmic reticulum Ca2+through the LTCC activation (sarcoendoplasmic reticulum, SR) membrane RyR2, make RyR2open, and release a large number of Ca2+, causes the cytoplasmic calcium ion concentration increased, starting the shrinkage of the cell. And diastolic phosphoprotein (phospholamban, PLB) phosphorylation to lift the sarcoplasmic reticulum calcium pump (sarcoendoplasmic reticulum Ca2+ATPase, SERCA2a) inhibition, increase its affinity with Ca2+, put most of intracytoplasmic sarcoplasmic reticulum Ca2+taken back.In recent years, the study of diastolic cardiac insufficiency mainly concentrated in the Ca2+/CaMK regulating pathway, existing research results reveal that changes in the structure of cardiac muscle have something with CaMK Ⅱ hyperactivity. When heart failure happens, CaMK Ⅱ after excessive activation of transcription inhibitors (HDACs) phosphorylation, and activate the myocardial enhancement factor2(MEF-2), launched the myocardial hypertrophy nuclear transcription factors. In addition, CaMK Ⅱ excessive activation of position change, not only the phosphorylation of adjacent LTCC, RyR2, but also make the PLB phosphorylation, leading to leakage of diastolic calcium, intracellular calcium overload, resulting in abnormal calcium transport in the cell.ObjectsBy yiqi huoxue medicine intervention in the rat model with diastolic dysfunction, detects calcium transport related protein and gene expression level. MethodsAdopt the method of narrow renal upper abdominal aorta to establish animal model of diastolic dysfunction in experimental animals were randomly divided into control group, model group, yiqi group, huoxue group and yiqi huoxue group. Through the Realtime-PCR to detect gene CaMK Ⅱ△B and CaMK Ⅱ△C expression level; By western blot detection protein CaMK Ⅱ, SERCA2a and expression level of PLB.Results1.4weeks after surgery (before dosing),model group compared with control group, the LVAWd+LVPWd, LVM have significant differences (P<0.05), but EF%, FS%, LVIDd have no obvious difference. After12weeks, model group compared with control group, the LVAWd+LVPWd increased significantly (P<0.05), increased LVM but there was no statistically significant difference. HR, LVIDd haveno statistical difference; Group compared with model group, yiqi huoxue LVAWd+LVPWd significantly decreased (P<0.05). After12weeks, the model group compared with control group, the MV E/A decreased (P<0.05), IVRT prolong significantly (P<0.05), EF%, FS%down but without statistical significance, HR and E’/A’have no statistical difference; Compared with model group, yiqi huoxue group MV peak E and MV E/A elevated (P<0.05), IVRT shortened (P<0.05), HR, EF, FS%, E’/A’have no statistical difference.2.1n the rat model group CaMK Ⅱ△B and CaMK II AC expression quantity increased significantly (P<0.05); Each treatment group compared with model group of CaMK Ⅱ expression was decreased (P<0.05), of which the yiqi huoxue group is more obvious thanyiqi group and huoxue group.3.CaMK Ⅱ protein model group’s expression level is higher than the control group (P<0.05), there is statistical significance; Yiqi group, huoxue group, yiqi huoxue group protein expression level had all decreased in the model group, but the level in yiqi huoxue group is obvious than yiqi and huoxue groups; SERCA2a protein expression model group were significantly lower than control group (P<0.05), there is statistical significance; Yiqi, huoxue group, yiqi huoxue group protein expression level increased in the model group, and better effect in yiqi huoxue group. conclusionConfirmed the parts ofmechanism of yiqi huoxue medicine treating diastolic heart function is by influencing myocardial cell calcium transport related gene and protein expression level, and yiqi huoxue combination has better therapeutic advantage.