| Acute Coronary Syndrome (ACS) has been a primary cause of mortality and morbidity of cardiovascular diseases. It is an essential treatment that restore reperfusion to ischemic myocardium through interventing culprit vessel for ACS patients. The prognosis of ACS has been improved significantly recently bacause percutaneous coronary intervention (PCI) has been applied widely in clinical practice, however, some problems have emerged in the same time. Some of patients with ACS after primary PCI can not restore complete myocardial reperfusion even then TIMI grade 3 showed by coronary angiography, which results in exacerbation in left ventricular remodeling and heart function, and makes an increase in major adverse cardiovascular events (MACE), such as heart failure (HF), sudden cardiac death. How to improve the prognosis of ACS patients with primary PCI become a top topic in the cardiovascular research field. The pectoral stuffiness pain manifested in ACS patients can be classified into "Xiongbi" or "Xintong" in traditional Chinese medicine (TCM), deficiency of qi and yin, and blood stasis are its main pathogenesis, so supplementing qi and nourishing yin, and activating blood circulation are an essential treatment method for ACS. Our previous studies demonstrated that Chinese herbs for supplementing qi and nourishing yin and activating blood circulation have a certain beneficial effects on the clinical symptoms of ACS patients, thus the aim of present clinical trial is to investigate its protective effects on the heart function of ACS patients with successful PCI.Objective To investigate the effects of Chinese herbs for supplementing qi, nourishing yin and activating blood circulation on heart function of ACS patients after successful PCI who were differentiated as deficiency of qi and yin and blood stasis syndrome according to TCM diagnosis. Methods 100 patients with ACS after successful PCI were divided randomly into Western Medicine (WM) treatment group (WMG, n=50) and combining treatment (adding Chinese herbs to WM) group (CHG, n=50). The follow-up was carried out at immediately after PCI and six-month and one-year after PCI. The investigating items included heart function grade (New York classification), TCM sympotom score, blood stasis syndrome score, MACE, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), ventricular wall motion index (VWMI) documented by echocardiograthy, and N-terminal pro-brain natriuretic peptide (NT-proBNP), hyper-sensitivity C-reactive protein (Hs-CRP), which were applied to evaluate the treatment effects on ACS patients after successful PCI. Results As compared with immediately after PCI, the patiens in both CHG and WMG have a significant increase in heart function grade (P<0.05) and LVEF (P<0.01), and a decrease in TCM sympotom score, blood stasis syndrome score, VWMI, LVEDV, LVESV, NT-proBNP and HS-CRP (P<0.01) at six-month after PCI. The patients in both groups have also a significant increase in heart function grade and LVEF (P<0.01), and a decrease in TCM sympotom score, blood stasis syndrome score, VWMI, LVEDV, LVESV, NT-proBNP and HS-CRP (P<0.01) at one-year after PCI. There were no significant difference in all above items between six-month and one-year after PCI (P>0.05) in patients in both groups. Moreover heart function grade, VWMI, LVEDV, LVESV, NT-proBNP, and HS-CRP were improved obviously in CHG than WMG (P<0.05), LVEF, TCM sympotom score and blood stasis syndrome score were improved obviously in CHG than WMG (P<0.01) at six-month and one-year after PCI. During the period of one-year follow-up,3 MACE and 11 MACE occured in CHG and WMG respectively, the event rate was lower in CHG than that in WMG (P<0.05). Conclusion The Chinese herbs for supplementing qi, nourishing yin and activating blood circulation could improve heart function, reduce incidence of MACE of ACS patientis with successful PCI. Therefore, it will have a certain beneficial effect for the prognosis of ACS patients with successful PCI. Objective To study the effects of salvianolic acid B(Sal B), a pure compound extracted from Salvia miltiorrhiza, on maturation and immune function of monocyte-derived dendritic cells (DCs) induced by oxidized-low density lipoprotein (OX-LDL), and explore its possible mechanisms. Methods Human monocytes were seperated and immature DCs derived. Then the PBS control group (CTL), the Sal B group, the Ciglitazone group (CIG), the OX-LDL group, Sal B and OX-LDL group (Sal B+OX-LDL), Ciglitazone and OX-LDL group (CIG+OX-LDL), SB203580 and OX-LDL group, SP600125 and OX-LDL group were randomly set up. The immunophenotypic expression (CD40, CD86, CD1a, and HLA-DR) and the expression of Toll-like receptors (TLRs) such as TLR2, TLR3, TLR4, and TLR7 were analyzed by Flow Cytometry. The cytokines secretions of culture supernatants (IL-12, TNF-a) were measured with ELISA. The protein level of phosphorylated P38MAPK, ERK1/2, JNK, myeloid differentiation-inducing protein 88 (MyD88), and peroxisome proliferator-activated receptor (PPAR)-y were measured with western blot. The expression of PPAR-γmRNA was measured with reverse transcription-polymerase chain reaction (RT-PCR). Results Compared with CTL group, OX-LDL increased the levels of immunophenotypic expression (CD40, CD86, CD1a, and HLA-DR) and cytokine secretions (TNF-a and IL-12) (P<0.01). Compared with OX-LDL treated group, Sal B pretreatment group reduced OX-LDL induced immunophenotypic expression of DCs (CD40, CD86, CDla and HLA-DR). Compared with OX-LDL treated group, the group of Sal B pretreatment attenuated OX-LDL induced cytokine secretions of DCs (IL-12 and TNF-a). Ciglitazone pretreatment demonstrated the same effects as Sal B (P>0.05). Compared with CTL group, the expressions of TLR2, TLR3, and TLR7, especially TLR4 were increased in OX-LDL group (P<0.05 and P<0.01). Sal B pretreatment could depress the expression of TLR4 induced by OX-LDL in DCs (P<0.01). Compared with CTL group, the protein levels of MyD88, phosphorylated P38MAPK, ERK1/2,and JNK were up-regulated significantly (P<0.01). Sal B pretreatment could depress the expression of MyD88 (P<0.01), phosphorylated P38MAPK (P<0.05), and ERK1/2 (P<0.05), but not phosphorylated JNK(P>0.05). SB203580, a special inhibitor of P38, could also reduce the expression of phosphorylated P38MAPK and ERK1/2(P<0.01), but not phosphorylated JNK(P>0.05). SP600125, a special inhibitor of JNK, only decreased the level of phosphorylated JNK(P<0.01), but not phosphorylated P38MAPK and ERKl/2(P>0.05). Interestingly, both SP600125 and SB203580 significantly reduced IL-10 and TNF-a production (P<0.01). Next, we apply RNA interference (RNAi) to inhibite PPAR-y activity by knocking down PPAR-y with specific siRNA. When PPAR-y was downregulated by specific siRNA, Sal B failed to attenuate OX-LDL-induced upregulation on membrane expressions of CD40, CD86, CD1a, and HLA-DR of DCs, and the secretions of IL-12 and TNF-a production in culture medium. The expression of p38 and ERK1/2 were downregulated in OX-LDL-treated DCs in the presence of Sal B or ciglitazone, and this effect could be partly reversed by PPAR-y siRNA. Moreover, the effect of Sal B on PPAR-y at not mRNA level but protein level. Conclusions Sal B inhibited OX-LDL-induced maturation and immune function of DCs, which was similar to Ciglitazone. P38 and ERK1/2 MAPK pathway mediated by TLR-4 is involved in OX-LDL-induced DCs maturation, and this cascade could be blocked by Sal B through activating PPAR-y. Above effect of Sal B showed in the present experiment might contribute to regulating the immune pathogenesis of AS.
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