Ya-Fang Tan1,2, Juan Yu3, Wen-Jun Pan1,2, Jian-Yong Qi1,2, Min-Zhou Zhang4,5. 1. AMI Key Laboratory of Chinese Medicine in Guangzhou, Guangdong Province Hospital of Chinese Medicine, the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Science, Guangzhou, 510006, China. 2. Intensive Care Research Team of Traditional Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Science, Guangzhou, 510006, China. 3. Animal Laboratory, Guangdong Province Hospital of Chinese Medicine, Guangzhou, 510006, China. 4. AMI Key Laboratory of Chinese Medicine in Guangzhou, Guangdong Province Hospital of Chinese Medicine, the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Science, Guangzhou, 510006, China. minzhouzhang8@163.com. 5. Intensive Care Research Team of Traditional Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Science, Guangzhou, 510006, China. minzhouzhang8@163.com.
Abstract
OBJECTIVE: To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills (, SXJ) on myocardial ischemia and reperfusion (I/R) injury. METHODS: Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion, the mice were then divided into the sham group (n=7), the I/R group (n=13), the tirofiban group (TIR, positive drug treatment, n=9), and the SXJ group (n=11). Infarct size (IS), risk region (RR), and left ventricle (LV) were analyzed with double staining methods. In addition, H9C2 rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro. The phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2), protein kinase B (AKT), glycogen synthase kinase-3β (GSK3β), and protein expression of GATA4 in nucleus were detected with Western blot assay. RESULTS: The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group (SXJ, 22.4% ±6.6%; TIR, 20.8%±3.3%; vs. I/R, 35.4%±3.7%, P<0.05, respectively). In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3β and nuclear expression of GATA4. CONCLUSION: SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3β and GATA4 signaling pathways.
OBJECTIVE: To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills (, SXJ) on myocardial ischemia and reperfusion (I/R) injury. METHODS:Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion, the mice were then divided into the sham group (n=7), the I/R group (n=13), the tirofiban group (TIR, positive drug treatment, n=9), and the SXJ group (n=11). Infarct size (IS), risk region (RR), and left ventricle (LV) were analyzed with double staining methods. In addition, H9C2rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro. The phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2), protein kinase B (AKT), glycogen synthase kinase-3β (GSK3β), and protein expression of GATA4 in nucleus were detected with Western blot assay. RESULTS: The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group (SXJ, 22.4% ±6.6%; TIR, 20.8%±3.3%; vs. I/R, 35.4%±3.7%, P<0.05, respectively). In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3β and nuclear expression of GATA4. CONCLUSION: SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3β and GATA4 signaling pathways.
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Keywords:
Chinese medicine; GATA4; Suxiao Jiuxin Pills; mouse; myocardial ischemia and reperfusion injury