Abstract:

Objective To observe the effect of sulfur dioxide （SO₂） on the myocardial fibrosis（MF） after acute myocardial ischemic injury in the rats， and to explore its mechanism. Methods Twenty-four male SD rats were randomly divided into control group （untreated）， isoproterenol （ISO） group （treated with ISO）， ISO+ SO₂ group （treated with ISO and SO₂）， and SO₂ group （treated with SO₂）， and there were six rats in each group. The acute myocardial ischemic injury model rats in ISO group and ISO+ SO₂ group were induced by intraperitoneal injection with a high dose of ISO （50 mg·kg^－1·d^－1） for 2 d. After successful modeling， the rats in ISO+ SO₂ group and SO₂ group were treated with Na₂SO₃ solution （0.54 mmol·kg^－1·d^－1） and NaHSO₃ solution （0.18 mmol·kg^－1·d^－1） for four weeks， while the rats in control group and ISO group were treated with equal volume of physiological saline intraperitoneally. The levels of myocardial troponin in plasma and electrocardiogram of the rats in various groups were detected；the left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） of the rats in various groups were detected by echocardiography；the collage deposition in myocadium tissue of the rats in various groups was detected by Masson staining and the collagen volume fraction （CVF） was calculated； the apoptotic rates of cardiomyocytes of the rats in various groups were detected by Tunel staining；the expression levels of autophagy-related proteins 3 （Atg3）， autophagy-related protein 5 （Atg5）， autophagy-related protein 16L1 （Atg16L1），aspartate proteolytic enzyme containing cysteine 3（Caspase-3）， aspartate proteolytic enzyme containing cysteine 9（Caspase-9）， matrix metalloproteinase 8 （MMP-8）， and tissue inhibitor of metalloproteinase 2 （TIMP-2） proteins in myocardium tissue of the rats in various groups were detected by Western blotting method. Results Compared with control group， the ST segment in electrocardiogram of the rats in ISO group and ISO+ SO₂ group showed elevation and the levels of myocardial troponin were increased （P<0.05），which indicated the acute myocardial ischemic injury models of the rats were established successfully. Compared with control group， the LVEF and LVFS of the rats in ISO group were decreased （P<0.05）， the CVF in myocadium tissue was increased （P<0.05）， the apoptotic rate of the cardiomyocytes was increased （P<0.05）， and the expression levels of Atg3， Atg5， Atg16L1， Caspase-3， Caspase-9， and MMP-8 proteins in myocardium tissue were increased（P<0.05）， and the expression level of TIMP-2 in myocardium tissue was decreased （P<0.05）. Compared with ISO group， the LVEF and LVFS of the rats in ISO+ SO₂ group was increased （P<0.05）， the CVF in myocadium tissue was decreased （P<0.05）， the apoptotic rate of the cardiomyocytes was decreased （P<0.05）， the expression levels of Atg3， Atg5， Atg16L1， Caspase-3， Caspase-9， and MMP-8 proteins in myocardium tissue were decreased（P<0.05）， and the expression level of TIMP-2 in myocardial tissue was increased （P<0.05）. Conclusion SO₂ can improve the MF after acute myocardial ischemic injury in the rats， and its mechanism may be related to the inhibition of excessive myocardial cell autophagy and reduction of the apoptosis of the cardiomyocytes.

Key words: Sulfur dioxide, Myocardial ischemia, Myocardial fibrosis, Cellular autophagy, Apoptosis