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Mechanism of QSYQ on anti-apoptosis mediated by different subtypes of cyclooxygenase in AMI induced heart failure rats.

Wang J, Li C, Cao Y, Wang Q, Lu L, Chang H, Wu Y, Han J, Wang W, Tu P, Wang Y - BMC Complement Altern Med (2015)

Bottom Line: Ultrasonography showed that EF and FS values decreased significantly and abnormal hemodynamic alterations were observed in model group compared to sham group.Apoptosis rates in myocardial tissue in the QSYQ group decreased compared with those in the model group.These findings provide experimental evidence for the beneficial effects of QSYQ in the clinical application for treating patients with HF.

View Article: PubMed Central - PubMed

Affiliation: Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. jwanghappy@163.com.

ABSTRACT

Background: Qi-shen-yi-qi (QSYQ), one of the most well-known traditional Chinese medicine (TCM) formulas, has been shown to have cardioprotective effects in rats with heart failure (HF) induced by acute myocardial infarction (AMI). However, the mechanisms of its therapeutic effects remain unclear. In this study, we aim to explore the mechanisms of QSYQ in preventing left ventricular remodelling in rats with HF. The anti-apoptosis an anti-inflammation effects of QSYQ were investigated.

Methods: Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham group, model group, QSYQ treatment group and aspirin group. Heart failure model was induced by ligation of left anterior descending (LAD) coronary artery. 28 days after surgery, hemodynamics were detected. Echocardiography was adopted to evaluate heart function. TUNEL assay was applied to assess myocardial apoptosis rates. Protein expressions of cyclooxygenase1 and 2 (COX1and COX2), Fas ligand (FasL), P53 and MDM2 were measured by western-blot. RT-PCR was applied to detect expressions of our subtype receptors of PGE2 (EP1, 2, 3, and 4).

Results: Ultrasonography showed that EF and FS values decreased significantly and abnormal hemodynamic alterations were observed in model group compared to sham group. These indications illustrated that HF models were successfully induced. Levels of inflammatory cytokines (TNF-α and IL-6) in myocardial tissue were up-regulated in the model group as compared to those in sham group. Western-blot analysis showed that cyclooxygenase 2, which is highly inducible by inflammatory cytokines, increased significantly. Moreover, RT-PCR showed that expressions of EP2 and EP4, which are the receptors of PGE2, were also up-regulated. Increased expressions of apoptotic pathway factors, including P53 and FasL, might be induced by the binding of PGE2 with EP2/4. MDM2, the inhibitor of P53, decreased in model group. TUNEL results manifested that apoptosis rates of myocardial cells increased in the model group. After treatment with QSYQ, expressions of inflammatory factors, including TNF-α, IL-6 and COX2, were reduced. Expressions of EP2 and EP4 receptors also decreased, suggesting that PGE2-mediated apoptosis was inhibited by QSYQ. MDM2 was up-regulated and P53 and FasL in the apoptotic pathway were down-regulated. Apoptosis rates in myocardial tissue in the QSYQ group decreased compared with those in the model group.

Conclusions: QSYQ exerts cardiac protective efficacy mainly through inhibiting the inflammatory response and down-regulating apoptosis. The anti-inflammatory and anti-apoptosis efficacies of QSYQ are probably achieved by inhibition of COXs-induced P53/FasL pathway. These findings provide experimental evidence for the beneficial effects of QSYQ in the clinical application for treating patients with HF.

No MeSH data available.


Related in: MedlinePlus

Potential mechanism of QSYQ efficacy. Treatment with QSYQ could attenuate inflammation and apoptosis in LAD-induced HF rats. One of the underlying therapeutic mechanisms of QSYQ is that it inhibits AA and P53/FasL pathway in a synergistic way
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Fig9: Potential mechanism of QSYQ efficacy. Treatment with QSYQ could attenuate inflammation and apoptosis in LAD-induced HF rats. One of the underlying therapeutic mechanisms of QSYQ is that it inhibits AA and P53/FasL pathway in a synergistic way

Mentions: In summary, administration of QSYQ could attenuate inflammation and apoptosis in LAD-induced HF rats. One of the probable underlying therapeutic mechanisms of QSYQ is that it inhibits AA and P53/FasL pathway in a synergistic way. The simplified mechanism is shown in Fig. 9. Our study provides experimental evidence for the beneficial effects of QSYQ in the clinical application for HF.Fig. 9


Mechanism of QSYQ on anti-apoptosis mediated by different subtypes of cyclooxygenase in AMI induced heart failure rats.

Wang J, Li C, Cao Y, Wang Q, Lu L, Chang H, Wu Y, Han J, Wang W, Tu P, Wang Y - BMC Complement Altern Med (2015)

Potential mechanism of QSYQ efficacy. Treatment with QSYQ could attenuate inflammation and apoptosis in LAD-induced HF rats. One of the underlying therapeutic mechanisms of QSYQ is that it inhibits AA and P53/FasL pathway in a synergistic way
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597456&req=5

Fig9: Potential mechanism of QSYQ efficacy. Treatment with QSYQ could attenuate inflammation and apoptosis in LAD-induced HF rats. One of the underlying therapeutic mechanisms of QSYQ is that it inhibits AA and P53/FasL pathway in a synergistic way
Mentions: In summary, administration of QSYQ could attenuate inflammation and apoptosis in LAD-induced HF rats. One of the probable underlying therapeutic mechanisms of QSYQ is that it inhibits AA and P53/FasL pathway in a synergistic way. The simplified mechanism is shown in Fig. 9. Our study provides experimental evidence for the beneficial effects of QSYQ in the clinical application for HF.Fig. 9

Bottom Line: Ultrasonography showed that EF and FS values decreased significantly and abnormal hemodynamic alterations were observed in model group compared to sham group.Apoptosis rates in myocardial tissue in the QSYQ group decreased compared with those in the model group.These findings provide experimental evidence for the beneficial effects of QSYQ in the clinical application for treating patients with HF.

View Article: PubMed Central - PubMed

Affiliation: Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. jwanghappy@163.com.

ABSTRACT

Background: Qi-shen-yi-qi (QSYQ), one of the most well-known traditional Chinese medicine (TCM) formulas, has been shown to have cardioprotective effects in rats with heart failure (HF) induced by acute myocardial infarction (AMI). However, the mechanisms of its therapeutic effects remain unclear. In this study, we aim to explore the mechanisms of QSYQ in preventing left ventricular remodelling in rats with HF. The anti-apoptosis an anti-inflammation effects of QSYQ were investigated.

Methods: Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham group, model group, QSYQ treatment group and aspirin group. Heart failure model was induced by ligation of left anterior descending (LAD) coronary artery. 28 days after surgery, hemodynamics were detected. Echocardiography was adopted to evaluate heart function. TUNEL assay was applied to assess myocardial apoptosis rates. Protein expressions of cyclooxygenase1 and 2 (COX1and COX2), Fas ligand (FasL), P53 and MDM2 were measured by western-blot. RT-PCR was applied to detect expressions of our subtype receptors of PGE2 (EP1, 2, 3, and 4).

Results: Ultrasonography showed that EF and FS values decreased significantly and abnormal hemodynamic alterations were observed in model group compared to sham group. These indications illustrated that HF models were successfully induced. Levels of inflammatory cytokines (TNF-α and IL-6) in myocardial tissue were up-regulated in the model group as compared to those in sham group. Western-blot analysis showed that cyclooxygenase 2, which is highly inducible by inflammatory cytokines, increased significantly. Moreover, RT-PCR showed that expressions of EP2 and EP4, which are the receptors of PGE2, were also up-regulated. Increased expressions of apoptotic pathway factors, including P53 and FasL, might be induced by the binding of PGE2 with EP2/4. MDM2, the inhibitor of P53, decreased in model group. TUNEL results manifested that apoptosis rates of myocardial cells increased in the model group. After treatment with QSYQ, expressions of inflammatory factors, including TNF-α, IL-6 and COX2, were reduced. Expressions of EP2 and EP4 receptors also decreased, suggesting that PGE2-mediated apoptosis was inhibited by QSYQ. MDM2 was up-regulated and P53 and FasL in the apoptotic pathway were down-regulated. Apoptosis rates in myocardial tissue in the QSYQ group decreased compared with those in the model group.

Conclusions: QSYQ exerts cardiac protective efficacy mainly through inhibiting the inflammatory response and down-regulating apoptosis. The anti-inflammatory and anti-apoptosis efficacies of QSYQ are probably achieved by inhibition of COXs-induced P53/FasL pathway. These findings provide experimental evidence for the beneficial effects of QSYQ in the clinical application for treating patients with HF.

No MeSH data available.


Related in: MedlinePlus