ABSTRACT
BACKGROUND: Hypoxia is a well-known factor in the promotion of apoptosis, which contributes to the development of numerous cardiac diseases, such as heart failure and myocardial infarction. Inhibiting apoptosis is an important therapeutic strategy for the treatment of related heart diseases caused by ischemia/hypoxic injury. Previous studies have demonstrated that BAG3 plays an important role in cardiomyocyte apoptosis and survival. However, the role of BAG3 in hypoxia-induced cardiomyocyte apoptosis remains to be clarified. Here, we demonstrate that BAG3 is induced by hypoxia stimuli in cultured cardiomyocytes. METHODS: BAG3 expression level was measured in H9c2 cells treated with hypoxia for 48 h. Cell proliferation and apoptosis were tested using MTT assay and Annexin V FITC-PI staining assay, respectively. The mRNA or protein expression level of BAG3, LC3-I, LC3-II, Atg5, NF-x03BA;B p65 and phosphorylated NF-x03BA;B p65 were assessed by qRT-PCR and western blot assay, respectively. Resluts: Overexpression of BAG3 inhibited cell apoptosis and promoted proliferation in hypoxia-injured H9c2 cells. Furthermore, autophagy and NF-x03BA;B were activated by BAG3 overexpression, and the NF-x03BA;B inhibitor PDTC could inhibit the activation of autophagy induced by BAG3 overexpression. In addition, the autophagy inhibitor 3-MA partly impeded the inhibitory effect of BAG3 on hypoxia-induced cardiomyocyte apoptosis. CONCLUSION: these results suggested that overexpression of BAG3 promoted cell proliferation and inhibited apoptosis by activating autophagy though the NF-x03BA;B signaling pathway in hypoxia-injured cardiomyocytes.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Apoptosis/genetics , Autophagy/genetics , Myocytes, Cardiac/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Animals , Antioxidants/pharmacology , Apoptosis Regulatory Proteins/metabolism , Autophagy-Related Protein 5/genetics , Autophagy-Related Protein 5/metabolism , Blotting, Western , Cell Hypoxia , Cell Line , Cell Survival/genetics , Gene Expression , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Myocytes, Cardiac/cytology , Proline/analogs & derivatives , Proline/pharmacology , RNA Interference , Rats , Reverse Transcriptase Polymerase Chain Reaction , Thiocarbamates/pharmacology , Transcription Factor RelA/antagonists & inhibitors , Transcription Factor RelA/genetics , Transcription Factor RelA/metabolism , Up-RegulationABSTRACT
OBJECTIVE: To observe the effect of external application of Zhuangshenling Recipe (ZR) combined with Western medicine (WM) on the heart function of chronic heart failure (CHF) patients of Xin-Shen yang deficiency, interior retention of water-fluid syndrome (XSYDIRWFS). METHODS: Totally 140 CHF patients of XSYDIRWFS were randomly assigned to two groups, the treatment group and the control group, 70 in each group. All patients received WM therapy. Those in the treatment group were applied with ZR at Xinshu (BL15) and Shenshu (BL23), while those in the control group were applied with placebos at Xinshu (BL15) and Shenshu (BL23). The therapeutic course for all was 12 weeks. The integrals of TCM syndrome, grading of cardiac function, brain natriuretic polypeptide (BNP), and 6 min walking distance were observed before and after treatment. RESULTS: After twelve weeks of treatment, the effective rate of improved grading of cardiac function, the total effective rate of TCM syndrome efficacy, and the BNP level were obviously better in the treatment group (P < 0.05). There was no statistical difference in 6 min walking distance between the two groups (P > 0.05). CONCLUSION: External application of ZR combined with WM could improve the heart function of CHF patients of XSYDIRWFS.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Heart Failure/drug therapy , Aged , Chronic Disease , Female , Humans , Male , Middle Aged , Treatment Outcome , Yang Deficiency/drug therapyABSTRACT
OBJECTIVE: To explore the cardiac protective effect of integrative therapy in acute myocardial infarction (AMI) with elevated ST segment after reperfusion. METHODS: Sixty-four AMI patients who having received decimalization by thrombolysis were assigned to two groups by retrospective analysis, 36 patients in the treated group and 28 in the control group. Both were treated by intravenous administering of urokinase for thrombolysis, and to the treated group, intravenous dripping of Xueshuantong Injection (, XST) was added. Serum levels of myocardial associated enzymes were monitored before treatment and at various time points after thrombolysis, and the heart function parameters were detected with color echocardiography before treatment and on the 7th and 14th day of treatment. The patients were followed up for 6 months to observe the incidence of cardiac events. RESULTS: The differences between groups at the peak and peak appearing time of creatine kinase and creatine kinase isoenzyme were not significant. All the heart function parameters on the 7th and 14th day in the treated group were improved and superior to those at the corresponding time points in the control group (P<0.05, P<0.01). Incidence of some heart events in the treated group within the 6-month follow-up period was lesser than that in the control group (P<0.05). CONCLUSION: XST Injection could provide effective protection for the heart after reperfusion.
