Myocardial Substrate Metabolic Remodeling in Heart Failure / 中国实验方剂学杂志

Myocardial substrate metabolism is severely impaired after heart failure, and the selection and utilization of substrates, such as glucose and fatty acids, are remodeled, resulting in insufficient myocardial productivity, cardiac dysfunction and progressive left ventricular remodeling. It is believed traditionally that the heart changes from fatty acid metabolism to glucose metabolism during heart failure, which however is contradictory with some findings in recent years. No consistent conclusion can be drawn from studies on the changes of myocardial energy substrate metabolism and its regulatory mechanism after heart failure. Metabolic treatment for heart failure has developed slowly. Therefore, it is necessary to explore the reasons for heterogeneity of these conclusions for defining the metabolic patterns of heart failure substrates and developing metabolically targeted drugs. This review summarizes the metabolic patterns and regulatory mechanisms of normal myocardium under physiological conditions, focuses on the elaboration and comparison of myocardial substrates metabolic abnormalities in heart failure induced by ischemic heart disease, pressure load, volume load and dilated cardiomyopathy in such aspects as etiology, severity, duration of heart failure, species studied, animal models and metabolic detection methods, and makes a preliminary analysis on the consistency and differences of relevant conclusions in various studies, and discusses the future trend of metabolic treatment, with the aim to summarize the rules and molecular mechanism of glucose metabolism and fatty acid metabolism after heart failure and provide clues for the research of metabolic targeted therapy.

Current situation and disease burden of allergic alveolitis in greenhouse farmers in China / 中国实用内科杂志

Farmer's lung disease(FLD) is a common form of occupational hypersensitivity pneumonitis(HP)(also termed “greenhouse lung”). FLD often occurs in greenhouse farmers due to the long-term exposure to high temperatures, humidity, poor air ventilation and high intensity of microorganism in soils in the closed environment of greenhouses. Greenhouse lung has a high disability rate and poor prognosis if not diagnosed or treated in time, which is a heavy burden to the society. Therefore, it is imperative to pay attention to early identification and epidemiological monitoring, and to evaluate the disease burden, which is of great significance to formulating public health measures to prevent the disease.

Huotan Jiedu Tongluo decoction alleviates early atherosclerosis of rabbits by inhibiting eNOS uncoupling pathway / 中国中药杂志

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.

Study on establishing animal model of myocardial infarction of blood-stasis and Xin-qi deficiency syndrome or blood-stasis and Xin-yang deficiency syndrome type / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the method for establishing animal model of integrative medical disease/ syndrome and its evaluation.</p><p><b>METHODS</b>Rat myocardial (heart failure) model was established by anterio-descending coronary arterial ligation, and treated by nitric oxide synthase inhibitor 9-12 weeks after operation to induce hypertension and aggravate heart failure. The model rat was observed 12 weeks to collect the information of four-diagnosis, for visceral qi-blood and excess-deficiency syndrome differentiation in combining with the eight-principal syndrome differentiation according to the standard of deficiency syndrome and blood-stasis syndrom issued by Chinese Association of integrative medicine.</p><p><b>RESULTS</b>After modeling, the model rats revealed ascended ST segment and abnormal Q-wave in ECG, with the visceral ratio, left ventricular area and myocardial collagen content significantly more than those in the sham-operative group (P < 0.01), showing a blood-stasis syndrome. Besides, Xin-qi deficiency syndrome, exhibiting as quickened heart rate, shortened swimming time and lowered cardiac function, appeared in the model rats (P < 0.01), which was aggravated in the late stage due to the increased blood pressure and deteriorated cardiac function, even revealed the manifestation of Yang-deficiency syndrome as low body temperature and polyuria.</p><p><b>CONCLUSION</b>The basic thinking path of TCM animal disease/syndrome model establishment and evaluation should adopt the normative, mature and unified standard and methods formed in clinical and experimental study of integrative medicine.</p>

Effect of Huoxue injection on oxidized low-density lipoprotein induced activation of human umbilical vein endothelial cells / 中国中药杂志

<p><b>OBJECTIVE</b>To observe effect of Huoxue injection on the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), the adherence of monocytes to endothelial cells, and the regulation role of nuclear factor kappa B (NF-kappaB) in cultured human umbilical vein endothelial cells (HUVEC) injury induced by the oxidized low-density lipoprotein (ox-LDL).</p><p><b>METHOD</b>The ox-LDL (100 mg x L(-1)) was added to the cultured HUVEC to prepare the injury model of HUVEC. The adhesive percentage between HUVEC treated with ox-LDL and monocytes was determined by protein quantification. Expression of mRNA and protein of ICAM-1 and VCAM-1 were determined by RT-PCR and flow cytometry respectively. The percentage of positive cells and the ratio of nuclei and cytoplasm of NF-kappaB p65 staining in HUVEC the were examined by cell immunochemistry.</p><p><b>RESULT</b>Treatment of HUVEC with ox-LDL for 12, 24 hours significantly increased adhesion of monocytes to HUVEC and enhanced the expressions of mRNA and protein of ICAM-1 and VCAM-1. The percentage of positive cells and the ratio of nuclei and cytoplasm of NF-kappaB p65 staining in HUVEC were significantly increased after treatment with ox-LDL for 24 hours. Huo Xue Injection could significantly inhibit the adhesion between monocyte and HUVEC, the expression of mRNA and protein of ICAM-1 and VCAM-1, and declined the percentage of positive cells and the ratio of nuclei and cytoplasm of NF-kappaB p65 staining in HUVEC. The effects were strengthened with increasing the deal of Huoxue injection.</p><p><b>CONCLUSION</b>Huoxue injection has an inhibitory effect on the adherence of monocytes to HUVEC, probably by way of down-regulating the expression of mRNA and protein of ICAM-1 and VCAM-1 in HUVEC. The mechanism is probably associated with inhibiting the activation of NF-kappaB p65 of HUVEC. The effects of Huoxue injection can bring about the protective effect to endothelial cells injury induced by ox-LDL.</p>

Characteristics of TCM syndrome and appraisal with echocardiography in heart failure rats after myocardial infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the characteristics of the TCM syndrome and the changes of ventricular structure and function in heart failure (HF) rats after- myocardial infarction (MI).</p><p><b>METHODS</b>Rats were randomly divided in to the model group and the sham-operative group. The HF rat with MI model was induced by ligation of the left coronary artery. Eight weeks after operation, appraisal on TCM syndrome revealed in the model was made from the aspects of general status, breathing frequency, heart rate, exhausting swimming time and electrocardiogram, and left ventricular structure and function were observed with echocardiography.</p><p><b>RESULTS</b>Eight weeks after operation, as compared with those in the sham group, in the model group, the heart rate and breathing frequency were accelerated, the exhausting swimming time shortened, the echocardiogram parameters such as interventricular septum end-diastole thickness (IVSTd), posterior wall end-diastole thickness (PWTd), posterior wall end-systolic thickness (PWTs), ejection fraction (EF) and fractional shortening (FS) of the left ventricular reduced (P < 0.01), while left ventricular end-diastolic dimension (LVDd) and end-systolic dimension (LVDs) obviously increased (P < 0.01). In 12 leads electrocardiogram, the leads of ST segment elevated and abnormal Q wave increased. Additionally, the ratio of whole heart weight/body weight increased (P < 0.05).</p><p><b>CONCLUSION</b>The HF rats after MI manifests Xin-qi deficiency and blood stasis syndrome, and shows the pathological changes of left ventricular remodeling and function impairment.</p>

Comparative study on early application of the recipe for activating blood circulation and the recipe for supplementing qi for inhibiting left ventricular remodeling and apoptosis in rats with heart failure / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the characteristics of early application of the recipe for activating blood circulation and the recipe for supplementing qi for inhibiting left ventricular remodeling and apoptosis in rats with heart failure.</p><p><b>METHOD</b>The left coronary artery occlusion was conducted to establish the rat model of heart failure after myocardial infarction. The model rats were randomly divided into 5 groups, including model group, activating blood circulation group (8 g x kg(-1)), supplementing qi group (8 g x kg(-1)), activating blood circulation plus supplementing qi group (16 g x kg(-1)), and captopril group (10.125 g x kg(-1)), and a sham operation group was set up as negative control group. The drugs were administrated on the second day after myocardial infarction with a therapeutic course of 4 weeks or 8 weeks. The heart function was detected by impedance method; Pathological staining and image analysis were used to determine the perimeter and the area of left ventricular cavity, and myocardial nuclei number and collagen content per unit area; Apoptosis percentage of the myocardial cell was detected by TUNEL and the content of Ang II in the cardiac muscle was measured by radioimmunoassay.</p><p><b>RESULT</b>In comparison with the model group, the function of left ventricular contraction function improved, the area of left ventricular cavity diminished, and proliferation of collagen, content of Ang II and apoptosis percentage of the myocardial cell reduced in all of the treatment groups (P < 0.05 or P < 0.01). After treatment of 8 weeks, the activating blood circulation group was similar to the sham operation group in improvement of cardiac index, and decreases of the area of left ventricular cavity and the content of Ang II; Apoptosis percentage of the myocardial cell in the activating blood circulation group was significantly lower than that in the supplementing qi group.</p><p><b>CONCLUSION</b>Both the recipes for activating blood circulation and for supplementing qi can inhibit left ventricular remodeling and myocardial apoptosis, and delay development of heart failure, with the best effect in the activating blood circulation group after treatment of 8 weeks.</p>

Study on cardiac gene expression microarray and recipe for activating blood circulation and supplementing qi on heart of rats with post-infarction heart failure / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of recipe for activating blood circulation and supplementing Qi (RAS) on cardiac functional structure in rats with post-infarction heart failure (PIHF).</p><p><b>METHODS</b>Rat model of PIHF was established by left coronary artery ligation. Left ventricular samples of model rats from infarcted or peri-infarcted area were obtained at PIHF formation stage and stable stage (10 days and 8 weeks respectively after operation), the total RNA extracted and detected using 6 pieces of rat's 40s gene microarray (4096 genes/microarray), the data were analyzed using software as Genespring, Treeview, Clustering and SOM. Besides, RAS was used to treat the model rats beginning from 4 weeks after modeling and lasted for 4 weeks, changes of heart function and cardiac coefficient before and after treatment were observed by impedance method with Captopril as positive control.</p><p><b>RESULTS</b>(1) Genespring analysis showed thousands of genes differential expression (upper or down regulated), including 13 kinds of gene involving energy metabolism, myocardial cytoskeleton, fibrosis, etc. which, in the infarcted area at heart formation stage were 1086 genes and at the stable stage, 724 genes, while in the peri-infarcted area, formation stage 196 genes and stable stage 97 genes. (2) After RAS or Captopril treatment, the heart function improved significantly, with the stroke volume, cardiac output and cardiac index increased significantly (P < 0.01). RAS could also improve the cardiac coefficient of model rats, as compared with that in untreated model, P < 0.01, compared with that in the sham-operated rats, P < 0.05.</p><p><b>CONCLUSION</b>PIHF is a kind of overload heart disease with multiple genes abnormality. RAS could improve the heart function and histologic indexes, so as to treat the heart failure.</p>

Effect of different drug dosage to activate blood circulation and to nourish qi on cardiac function and structure of congestive heart failure rats after acute myocardial infarction / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of different drug dosage to activate blood circulation and to nourish Qi on cardiac function and structure of heart failure rats after acute myocardial infarction.</p><p><b>METHOD</b>The congestive heart failure post cardiac infarction rats models subjected to left coronary occlusion were made and given different dosage of drug of Huoxue Yiqi and captopril (positive control) from 4 weeks to 8 weeks after operation. The cardiac function before and after using drugs were observed by impedance methods.</p><p><b>RESULT</b>Treated by different dosage of drug of Huoxue Yiqi and captopil, cardiac function of heart failure rats after acute myocardial infarction improved, SV, CO, CI(P < 0.01); at the same time, prescription of Huoxue Yiqi and Qixue could improve the model rats' heart coefficient, VS SHAM(P > 0.05), but prescription of Yiqi Huoxue and captopril could not improve it.</p><p><b>CONCLUSION</b>Drug to activate blood circulation and to increase qi can treat heart failure rats after acute myocardial infarction, through improving their function and structure. At the same time, more dosage of drug to activate blood circulation and to increase qi(Huoxue/Yiqi drug) may improve the model rats' heart coefficient.</p>

Comparative study on effect of recipe for activating blood circulation and replenishing Qi on left ventricular remodeling in rats with left heart failure after myocardial infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>Comparative study to the effect of Chinese herbal medicine on left ventricular remodeling in rats with left heart failure after myocardial infarction (MI).</p><p><b>METHODS</b>Rat's model of left heart failure after myocardial infarction was treated with injection for activating blood circulation (ABCI, consisted of R. Salviae miltiorrhizea; Rh. Ligusticum wallichii and F1. Carthamus tinctorius) and injection for replenishing Qi (RQI, consisted of R. Codonopsis Pilosulae and R. Astragalus membranaceus) respectively. The effect of treatment were evaluated by observing and comparing the changes of heart morphological structure, collagen element, heart weight/body weight ratio (HW/BW), left intraventricular area (LVA), ratio of ventricular wall thinning in MI area and myocardial nuclei number (MNN) per square area.</p><p><b>RESULTS</b>In comparison with the model group, the reduction of collagen tissue around myocardial cells in living area of MI, HW/BW and LVA of ABCI and RQI group were lower, and MNN per square area was higher significantly (all P < 0.05).</p><p><b>CONCLUSION</b>Both ABCI and RQI, though without positive myodynamia, showed certain inhibitory effect of left ventricular remodeling in rats with left heart failure after MI.</p>