Ruiying Wang1,2,3,4, Min Wang1,2,3,4, Jiahui Zhou1,2,3,4, Tianyuan Ye1,2,3,4, Xueheng Xie5, Dong Ni6, Jingxue Ye1,2,3,4, Qiaoling Han7, Caixia Di7, Liang Guo7, Guibo Sun1,2,3,4, Xiaobo Sun1,2,3,4. 1. Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Beijing 100193, China. 2. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China. 3. Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. 4. Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. 5. Harbin University of Commerce, Harbin 150076, China. 6. Jilin Agricultural University, Changchun 130118, China. 7. Shiyao Yinhu Pharmaceutical Co., Ltd., Yuncheng 044000, China.
Abstract
BACKGROUND: Shuxuening injection (SXNI) has a good effect on cardiovascular and cerebrovascular diseases. Here, our study aims to investigate whether SXNI have the protective effect on myocardial ischemia-reperfusion injury (MIRI) and elucidate the mechanism of SXNI's cardiac protection. METHODS: In this experiment, the coronary arteries of Sprague-Dawley (SD) rats were ligated for the induction of a MIRI model. TTC staining and haematoxylin-eosin (HE), as well as troponin I (TnI), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and CK-MB levels, were used to detect the protective effect of SXNI. In rat cardiac tissue, superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) activities and glucose-regulated protein 78 (GRP78), calreticulin (CRT), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12 expression levels were detected. In rat serum, the levels of inflammatory factors, including high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, tumour necrosis factor-α, interleukin-6 (IL-6) and IL-1β, were measured by Elisa. In the rat arterial tissue, Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) expression was measured by western blot. In the rat plasma, ELISA was used to assay the levels of coagulation and plasmin system indicators, including platelet activating factor, endothelin, tissue factor (TF), plasminogen inhibitor, thromboxane B2, plasma fibrinogen. RESULTS: The results showed that SXNI can reduce the infarct size of myocardial tissue, decrease the myocardial enzyme and TnI levels and decrease the degree of myocardial damage compared with the model group. Additionally, SXNI can increase the activity of antioxidant enzymes, reduce the MDA level and decrease the GRP78, CRT, CHOP and caspase-12 expression levels. SXNI also decreased the levels of inflammatory cytokines in rat serum, lowered the level of procoagulant molecules in plasma and reduced the TLR4/NF-κB expression. CONCLUSIONS: SXNI has protective effect on MIRI mainly by inhibiting oxidative stress and endoplasmic reticulum stress (ERS), thereby regulating TLR4/NF-κB pathway to reduce inflammation, and lowing procoagulant-related factors levels to reduce the risk of thrombosis. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Shuxuening injection (SXNI) has a good effect on cardiovascular and cerebrovascular diseases. Here, our study aims to investigate whether SXNI have the protective effect on myocardial ischemia-reperfusion injury (MIRI) and elucidate the mechanism of SXNI's cardiac protection. METHODS: In this experiment, the coronary arteries of Sprague-Dawley (SD) rats were ligated for the induction of a MIRI model. TTC staining and haematoxylin-eosin (HE), as well as troponin I (TnI), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and CK-MB levels, were used to detect the protective effect of SXNI. In rat cardiac tissue, superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) activities and glucose-regulated protein 78 (GRP78), calreticulin (CRT), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12 expression levels were detected. In rat serum, the levels of inflammatory factors, including high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, tumour necrosis factor-α, interleukin-6 (IL-6) and IL-1β, were measured by Elisa. In the rat arterial tissue, Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) expression was measured by western blot. In the rat plasma, ELISA was used to assay the levels of coagulation and plasmin system indicators, including platelet activating factor, endothelin, tissue factor (TF), plasminogen inhibitor, thromboxane B2, plasma fibrinogen. RESULTS: The results showed that SXNI can reduce the infarct size of myocardial tissue, decrease the myocardial enzyme and TnI levels and decrease the degree of myocardial damage compared with the model group. Additionally, SXNI can increase the activity of antioxidant enzymes, reduce the MDA level and decrease the GRP78, CRT, CHOP and caspase-12 expression levels. SXNI also decreased the levels of inflammatory cytokines in rat serum, lowered the level of procoagulant molecules in plasma and reduced the TLR4/NF-κB expression. CONCLUSIONS: SXNI has protective effect on MIRI mainly by inhibiting oxidative stress and endoplasmic reticulum stress (ERS), thereby regulating TLR4/NF-κB pathway to reduce inflammation, and lowing procoagulant-related factors levels to reduce the risk of thrombosis. 2019 Annals of Translational Medicine. All rights reserved.
Authors: Jan Kristian Damås; Torgun Waehre; Arne Yndestad; Kari Otterdal; Aina Hognestad; Nils Olav Solum; Lars Gullestad; Stig S Frøland; Pål Aukrust Journal: Circulation Date: 2003-05-12 Impact factor: 29.690