Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium / 中国结合医学杂志

OBJECTIVE@#To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.@*METHODS@#A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.@*RESULTS@#DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).@*CONCLUSION@#DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Investigation of Evolution Rules of Phlegm and Blood Stasis Syndrome in Hyperlipidemia and Ath- erosclerosis by NMR-based Metabolic Profiling and Metabonomic Approaches / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore evolution rules of phlegm and blood stasis syndrome ( PBSS) in hyperlipidemia and atherosclerosis (AS) using NMR-based metabolic profiling and metabonomic approaches based on formulas corresponding to syndrome.</p><p><b>METHODS</b>Totally 150 SD rats were divided into the normal group, the model group, the Erchen Decoction (ED) group, the Xuefu Zhuyu Decoction (XZD) group, the Lipitor group, 30 in each group. The hyperlipidemia and AS rat model was duplicated by suturing carotid artery, injecting vitamin D3, and feeding with high fat diet. ED and XZD were used as drug probes. Blood samples were withdrawn at week 2, 4, and 8 after modeling. Blood lipids, blood rheology, histopathology and metabolomics were detected and analyzed. Results Results of blood lipids and pathology showed hyperlipidemia and early AS rat models were successfully established. At week 2 after modeling, levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) significantly increased, which reached the peak at week 4 and maintained at higher levels at week 8. ED exerted obvious effect in improving TC and LDL-C levels of early models, while XZD could greatly improve levels of TC and LDL-C of late models. Rheological results showed at week 2, there was no significant difference in whole blood viscosity, plasma viscosity, or hematocrit between the model group and the normal group (P > 0.05). At week 4 partial hemorheological indicators (such as plasma viscosity) were abnormal. Till week 8 whole blood viscosity, plasma viscosity, and hematocrit were significantly abnormal (P <0. 05, P < 0.01). As time went by, whole blood viscosity, plasma viscosity, and hematocrit showed gradual increasing tendency in the ED group, while they showed gradual decreasing tendency in the XZD group. Results of metabonomics showed significant difference in spectra of metabolites between the normal group and the model group. As modeling time was prolonged, contents of acetyl glucoprotein and glucose in the model group increased in late stage, which was in. line with results of blood lipids and hemorheology. ED showed more obvious effect in early and mid-term modeling (at week 2 and 4), and increased contents of partial metabolites (such as choline, phosphatidyl choline, glycerophosphocholine), but these changes in the XZD group were consistent with those of the model group. In late modeling (at week 8) XZD showed more obvious effect in improving contents of lactic acid, acetyl glycoprotein, LDL, creatine, choline, and glucose.</p><p><b>CONCLUSIONS</b>ED and XZD not only showed regulatory effects on lipid disorders, but also could improve dysbolism of Chos. In formulas corresponding to syndrome, damp-phlegm was main pathogenesis of hyperlipidema and AS in early and mid stages. Blood stasis syndrome began to occur along with it progressed. Phlegm can result in blood stasis and intermingles with stasis. Phlegm turbidity runs through the whole process.</p>

Effect of fulu baoxinping oral liquid in treatment of coronary heart disease patients with premature ventricular beat / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Fulu Baoxinping (FLBXP) oral liquid in the treatment of coronary heart disease patients with premature ventricular beat (PVB), differentiated as qi-yin deficiency with phlegm-stasis syndrome type.</p><p><b>METHODS</b>Adopting randomized, double-blinded, double-simulated, positive drug parallel controlled and multi-centered clinical research method, 240 patients enrolled were randomly assigned equally to the treatment group treated with FLBXP 10 mL (containing 13.33 g of crude drug) thrice a day and the control group treated with Wenxin Granule 9 g thrice a day. Meanwhile, simulator of the test or positive control drug was given to them all correspondingly. The therapeutic course for them all was 28 days. Efficacy on PVB and TCM syndrome was observed.</p><p><b>RESULTS</b>The markedly effective rate and total effective rate on PVB were 55.0% and 78.4% in the treatment group, and 37.2% and 53.1% in the control group, significant difference between groups was shown in comparison of both indexes (P < 0.05). Dynamic ECG showed the total number of PVB decreased for 3460.59 +/- 6516.56 beats/24 h in the treatment group, and for 2148.36 +/- 5129.47 beats/24 h in the control group, difference between them showed no statistical significance (P > 0.05). The TCM syndrome score in both groups was markedly decreased after treatment when compared with before treatment (P < 0.01); the differences of the treated and the control groups were -9.34 +/- 4.21 and -8.08 +/- 4.33 respectively, showing sigificant difference (P < 0.05).</p><p><b>CONCLUSION</b>FLBXP oral liquid has certain effect on PVB in CHD patients of qi-yin deficiency with phlegm-stasis syndrome type, no obvious adverse reaction was found in the clinical trial.</p>

Effect of Coptis root extract on gene expressions of perilipin and PPAR-gamma in aortic vulnerable atherosclerotic plaque of ApoE-gene knockout mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of coptis root extract (CRE) on the gene expressions of perilipin and peroxisome proliferator activated receptor gamma (PPAR-gamma) in atherosclerotic plaque of ApoE-gene knockout mice for exploring its plaque stabilizing action and possible mechanism.</p><p><b>METHODS</b>Thirty-three ApoE knockout mice, 6-8 weeks old, were fed with high-fat diet for 13 weeks. After mature atherosclerotic plaques being formed, the animals were randomly allocated into the control group, the CRE group, and the simvastatin group (as positive control) , 11 in each group. They were continuously fed with high-fat diet and to the two drug-treated groups, respective drugs in clinically recommended dose were given for another 13 weeks. Then all mice were sacrificed by the end of experiment. The morphology and composition of atherosclerotic plaques in 4 sections of aortic roots were examined with HE and Movat stain, the average number of fibrous caps buried in the plaque was observed and counted, and the gene expressions of perilipin and PPAR-gamma mRNA were determined by Real-time fluorescent quantitative PCR technology.</p><p><b>RESULTS</b>After treatment for 13 weeks, the number of fibrous caps and the gene expression of perilipin mRNA in the CRE group was significantly lower (P<0.05), but gene of PPAR-gamma mRNA was higher (P<0.01) than those in the model group.</p><p><b>CONCLUSION</b>In a clinically recommended dose, CRE can significantly decrease the frequency of plaque rupture in aorta of ApoE-gene knockout mice and do favour to plaque stability, its mechanism may be related to the promotion of PPAR-gamma mRNA expression and the inhibition of perilipin mRNA expression.</p>

Effects of some active ingredients of Chinese drugs for activating blood circulation and detoxicating on blood lipids and atherosclerotic plaque inflammatory reaction in ApoE-gene knockout mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of active ingredients from Chinese drugs for activating blood circulation and detoxicating, including notoginseng saponins (drug 1), Coptis chinensis (drug 2), giant knotweed rhizome (drug 3) and rhubarb (drug 4), on blood lipids and inflammatory reaction of aortic atherosclerotic plaques in ApoE knockout mice.</p><p><b>METHODS</b>ApoE knockout mice were fed with high-fat diet for 26 weeks, then they were randomized into 6 groups, the untreated model group and the test groups treated with various test drugs respectively. After ending the 13 weeks of treatment, all the mice were sacrificed with their blood lipids detected, and their heart and aorta were taken out to make slices with paraffin embedding. Four sections from aortic root of each mouse were chosen to measure and calculate the percentage of lipid core (LC) in the total area of plaque (TP) and the lipid/collagen ratio (L/C) in the plaque by HE and Movat staining respectively, and the mean value of the four sections was taken for analysis. The expressions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) in mice's aorta root were determined by immunohistochemical staining as well.</p><p><b>RESULTS</b>After being treated for 13 weeks, either the percentage of LC in TP and the L/C ratio was significantly lower in all the test drug treated groups than those in the model group, respectively (P < 0.01), especially prominent in the group treated with drug 3. Although lowering of the two indexes presented in all the 3 groups treated by drug 1, 2 and 3, significant difference still presented between drug 3 treated group vs drug 1 and 2 treated group (P < 0.05). As for the expressions of GM-CSF and TNF-alpha, in comparing with the untreated model group, significant decreasing of the TNF-alpha showed only in the drug 4 treated group, while that of GM-CSF could be found in all the test drug treated groups (P < 0.05).</p><p><b>CONCLUSION</b>All the 4 drugs tested in the recommended dosage can stabilize the vulnerable plaques in ApoE knockout mice by improving the constitution of plaque, among them, drug 3 and 4, the drugs possess both the actions of activating blood circulation and detoxicating, show more significant effect, and their mechanisms may be related to their actions in regulating lipid metabolism and inhibiting inflammatory reaction.</p>

Review on treatment of unstable atherosclerotic plaque with traditional Chinese medicine / 中国中西医结合杂志

Rupture of unstable atherosclerotic plaque is an essential pathogenetic mechanism of acute coronary syndrome (ACS), thereby, to stabilize the vulnerable plaque is of great importance for prevention and treatment of ACS. Recent study has shown the multi-target effects of traditional Chiese medicine intervention in stabilizing unstable atherosclerotic plaque is promising. The literatures involving this topic in recent years were reviewed in this paper.