Energy metabolism disorder and myocardial injury in chronic myocardial ischemia with Qi deficiency and blood stasis syndrome based on 2-DE proteomics / 中国结合医学杂志

<p><b>OBJECTIVE</b>To inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis (2-DE) map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome.</p><p><b>METHODS</b>Ameroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome.</p><p><b>RESULTS</b>The preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDITOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 (NAD+) alpha, NADH dehydrogenase (NAD) Fe-S protein 1, chain A (crystal structure of aldose reductase by binding domain reveals a new Nadph), heat shock protein 27 (HSP27), oxidoreductase (NAD-binding protein), antioxidant protein isoform, cardiac troponin T (cTnT), myosin (myosin light polypeptide), cardiac alpha tropomyosin, apolipoprotein A-I and albumin.</p><p><b>CONCLUSION</b>Down-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker(s) for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine.</p>

Establishment and evaluation on miniature pig model of ischemic coronary heart disease with qi-deficiency and blood-stasis syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the Chinese medical syndrome characteristics of the miniature pig model of coronary heart disease (CHD) made by chronic myocardial ischemia, and its correlation with heart structure and function.</p><p><b>METHODS</b>Chinese miniature pigs were randomly divided into two groups, 18 in the model group and 8 in the sham-operation group. CHD model was established by placing Ameroid narrow ring in the left anterior descending artery of pigs to induce chronic myocardial ischemia. Characteristics of Chinese medical syndrome in the model were evaluated 8-12 weeks after modeling by observing the general condition, tongue color, activity, hemorrheologic figures, electrocardiogram, coronary angiography, etc., as well as the cardiac structure and function detected by echocardiogram.</p><p><b>RESULTS</b>Compared with the sham-operation group, the modeled pigs showed, at end of the 8th week, pink purple tongue; decreased tail wagging frequency (P < 0.05 or P < 0.01); increased plasma and reduction viscosities (P < 0.05); and raised rigidity index (P < 0.01), with the stenosed diameter of coronary artery reaching 99%. Besides, echocardiogram showed decreased thickness of left ventricular end-systolic stage, end-diastolic stage and inter-ventricular septum end-diastolic stage; lowered ejection fraction and fractional shortening rate (P < 0.05 or P < 0.01), and dilated left ventricular end-diastolic diameter and left ventricular end-systolic diameter. The motion of ventricular wall was decreased orderly in levels from the mitral valve to the papillary muscle to the apex of heart.</p><p><b>CONCLUSIONS</b>CHD pig model made by chronic myocardial ischemia showed a Chinese medical qi-deficiency & blood-stasis syndrome. It indicated that a syndrome transition and conversion progress from blood-stasis to qi-deficiency & blood stasis occurred in the model animals at the 4th to 12th week. The created model provided a reliable basis for further studying rules of syndrome transition and conversion between qi deficiency and blood stasis, as well as on the Chinese medical theory of "blood is mother of qi".</p>