Study on Salvianolate Combined with Mesenchymal Stem Cells Autotransplantation in the Treatment of Acute Myocardial Injury
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Graphical Abstract
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Abstract
OBJECTIVE To investigate the effect of salvianolate combined with mesenchymal stem cells(MSCs) autotransplantation in the treatment of acute myocardial injury(AMI). METHODS MSCs were isolated from bone marrow of SD rats, cultured in the medium and incubated by salvianolate(100 mg·L-1). Immunofluorescence was used to detect the fluorescence expression of cTnI, NKx2.5 and GATA-4 in MSCs, Western blotting was used to detect the expression of cTnI, Cx43, Nkx2.5, GATA-4 and β-MHC. The animal model of AMI was prepared, and SD rats were randomly divided into five groups:sham operation group(PBS + saline), model group(PBS + saline), MSCs group(60 μL MSCs + saline), salvianolate group(PBS + 30 mg·kg-1 salvianolate) and salvianolate + MSCs group (60 μL MSCs + 30 mg·kg-1 salvianolate). After AMI model was established, SD rats in each group were administrated consecutively for seven days, once per day. And then the heart function parameters of each group were recorded, and the blood samples and heart tissue samples were collected after seven days. The myocardial infarction area was measured by TTC staining, the activity of CK-MB and LDH were detected by ELISA, HE staining was used to assess the pathological injury of myocardial tissue and TUNEL staining was used to detect the apoptosis of myocardial cells. RESULTS MSCs were successfully isolated and cultured, and with salvianolate induced, immunofluorescence results showed that the expression of cTnI, Nkx2.5 and GATA-4 increased significantly, Western blotting showed that the expression of cTnI, CX43, Nkx2.5, GATA-4 and β-MHC was significantly increased. After the AMI rat model was successfully prepared and treated, the results showed that compared with the model group, the levels of myocardial function parameters including FS, +dp/dtmax and -dp/dtmax in salvianolate + MSCs group increased significantly, while the levels of LVDEP and the CK-MB and LDH activity decreased significantly(P<0.01 or P<0.05). The results of TTC staining showed that compared with the model group, the myocardial infarct area of rats in each administration group decreased significantly, especially in the group of salvianolate + MSCs (P<0.01). HE staining results showed that the combination of salvianolate and MSCs could effectively alleviate the myocardial injury in AMI rats. TUNEL staining results showed that the number of positive cells in salvianolate + MSCs group was decreased and the degree of apoptosis decreased most obviously. CONCLUSION Salvianolate and MSCs autotransplantation can effectively alleviated AMI, this might be related to the differentiation of MSCs into cardiomyocytes, the improvement of hemodynamics, the reduction of myocardial enzyme activity, and the inhibition of apoptosis.
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