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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

Study designs. Left anterior descending (LAD) coronary artery was ligated to induce the heart failure (HF) model. Rats in the sham groups went through identical procedures except that their LAD arteries were not ligated. The rats alive after surgery were randomly divided into three groups, with ten rats in each group. There were also ten rats in the sham groups. QSYQ dissolved in water was given by oral gavage for 28 days at a total dosage of 0.175 g/kg on a daily base. Aspirin was given as a control drug at a dosage of 53.3 mg/kg
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Fig1: Study designs. Left anterior descending (LAD) coronary artery was ligated to induce the heart failure (HF) model. Rats in the sham groups went through identical procedures except that their LAD arteries were not ligated. The rats alive after surgery were randomly divided into three groups, with ten rats in each group. There were also ten rats in the sham groups. QSYQ dissolved in water was given by oral gavage for 28 days at a total dosage of 0.175 g/kg on a daily base. Aspirin was given as a control drug at a dosage of 53.3 mg/kg

Mentions: HF was induced by direct left anterior descending (LAD) ligation as described previously [34]. Briefly, SD rats were anaesthetized with 1 % pentobarbital sodium (50 mg/kg ip), and a left thoracotomy was performed. The LAD was ligated near its origin at the edge of the left atrium (Surgipro, CT, USA). The thorax was then closed. The rats were kept on a heating pad and monitored until the sedation wore off and they were awake. Live rats were then randomly divided into three groups: ten in the model group, 10 in the Aspirin group, and ten in the QSYQ group. Meanwhile, the ten rats in the sham-operated group without LAD ligation were investigated together. The QSYQ group was treated for 28 days by daily oral gavage of QSYQ with a total daily dose of 0.175 g/kg (Tasly Pharmaceutical Group Corporation. Tianjin, China, Series: 100706). QSYQ was dissolved in water. The fingerprints of QSYQ established by the HPLC-IT-TOF method were shown in Additional file 1. The sham-operated group and the model group received the same volume of water, and the Aspirin group was given the same volume of Aspirin solution (53.3 mg/kg) via oral gavage. The study designs were carried out as shown in Fig. 1.Fig. 1


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)

Study designs. Left anterior descending (LAD) coronary artery was ligated to induce the heart failure (HF) model. Rats in the sham groups went through identical procedures except that their LAD arteries were not ligated. The rats alive after surgery were randomly divided into three groups, with ten rats in each group. There were also ten rats in the sham groups. QSYQ dissolved in water was given by oral gavage for 28 days at a total dosage of 0.175 g/kg on a daily base. Aspirin was given as a control drug at a dosage of 53.3 mg/kg
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Study designs. Left anterior descending (LAD) coronary artery was ligated to induce the heart failure (HF) model. Rats in the sham groups went through identical procedures except that their LAD arteries were not ligated. The rats alive after surgery were randomly divided into three groups, with ten rats in each group. There were also ten rats in the sham groups. QSYQ dissolved in water was given by oral gavage for 28 days at a total dosage of 0.175 g/kg on a daily base. Aspirin was given as a control drug at a dosage of 53.3 mg/kg
Mentions: HF was induced by direct left anterior descending (LAD) ligation as described previously [34]. Briefly, SD rats were anaesthetized with 1 % pentobarbital sodium (50 mg/kg ip), and a left thoracotomy was performed. The LAD was ligated near its origin at the edge of the left atrium (Surgipro, CT, USA). The thorax was then closed. The rats were kept on a heating pad and monitored until the sedation wore off and they were awake. Live rats were then randomly divided into three groups: ten in the model group, 10 in the Aspirin group, and ten in the QSYQ group. Meanwhile, the ten rats in the sham-operated group without LAD ligation were investigated together. The QSYQ group was treated for 28 days by daily oral gavage of QSYQ with a total daily dose of 0.175 g/kg (Tasly Pharmaceutical Group Corporation. Tianjin, China, Series: 100706). QSYQ was dissolved in water. The fingerprints of QSYQ established by the HPLC-IT-TOF method were shown in Additional file 1. The sham-operated group and the model group received the same volume of water, and the Aspirin group was given the same volume of Aspirin solution (53.3 mg/kg) via oral gavage. The study designs were carried out as shown in Fig. 1.Fig. 1

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