Abstract
Purpose: To explore the cardioprotective effects and potential mechanisms of Shenxiong Glucose Injection (SGI) in rat acute myocardial infarction (AMI). Methods: AMI model was created by ligating left anterior descending coronary artery. After 7 days’ consecutive intravenous administration of SGI, serum samples were used to conduct biochemical analysis while hearts were excised and processed for infraction size, enzyme activity, histopathology and qPCR studies. Intracellular Ca 2+ {(Ca 2+ )i} overload in H9c2 cells was measured by laser scanning confocal microscope (LSCM). Results: In AMI rats, pretreatment with SGI significantly ameliorated myocardial histopathologic damage. It exerted cardioprotective effect by decreasing myocardial infarct size, electrocardiogram (ECG) ST segment elevation, and CK, cTnI, BNP levels in serum. In addition, SGI significantly decreased calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMK II) mRNA expression, but increased Ca 2+ -Mg 2+ -ATPase and Na+-K+-ATPase activities in myocardium. In doxorubicin (DOX)- induced H9c2 cells injury model, SGI reversed (Ca 2+ )i overload to protect cells. Conclusion: The results demonstrate SGI exerts cardioprotective effect by decreasing myocardial infarct size, restoring ST segment and reversing (Ca 2+ )i overload. It suggests that SGI may be a new clinical candidate to treat myocardial infarction. Keywords: Shenxiong glucose injection, Tanshinol, Ligustrazine, Myocardial infarction, Intracellular Ca 2+ overload, Calmodulin, Calmodulin-dependent protein kinase II
Highlights
Ischemic heart disease, commonly called coronary artery disease, is a disease characterized by reduced blood supply to the heart
The mRNA relative expression levels of Shenxiong Glucose Injection (SGI) ameliorates ECG and decreases biomarkers of acute myocardial infarction (AMI) injury in AMI rats The myocardial injury can lead to abnormal ST segment change, so ECG can reflect the myocardial injury directly
AMI injury resulted in significant ST segment elevation in the AMI group, which demonstrated that the AMI injury model of rats was successfully established
Summary
Commonly called coronary artery disease, is a disease characterized by reduced blood supply to the heart. Kinds of drugs such as aspirin, thrombolysis agents, β receptor blockers and ACE inhibitors have been used to treat AMI [2,3], AMI is still one of the major cause of ischemic heart diseases, and with high rate of morbidity and mortality [4]. The safer and more effective drugs still need to be explored for clinical use. SGI is known as Bai Se Tong, and its components are originated from danshen (Salvia miltiorrhiza Bge.) and chuanxiong (Ligusticum chuanxiong Hort.). It has been widely used in cerebral ischemia disease and other ischemic diseases in Asia. The active ingredients of SGI, have been confirmed to exhibit powerful protective effects on cardio-cerebrovascular disease in vitro and in vivo, and they have shown various pharmacological activities such as anti-oxidation, anti-apoptosis, and anticoagulation in the treatment of ischemic and infarction disease [57]
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