Abstract:

Objective To investigate the ameliorative effects of sulfur dioxide （SO₂） on myocardial fibrosis in the type 2 diabetes mellitus （T2DM） rats induced by streptozocin （STZ） and high glucose and high fat diet and the effects on apoptosis and transforming growth factor-β1（TGF-β1）/Smad family member 2/3（Smad2/3） pathway， and to clarify the possible molecular mechanisms of SO₂ in ameliorating diabetic myocardial fibrosis. Methods Forty male SD rats were randomly divided into control group， T2DM group， T2DM+SO₂ group， and SO₂ group. Except for control group and SO₂ group， the rats in T2DM and T2DM+SO₂ groups were used to establish the T2DM rat models by intraperitoneal injection of STZ （35 mg·kg^－1） and high glucose and high fat diet， and the rats in T2DM+SO₂ and SO₂ groups were injected intraperitoneally with exogenous SO₂ donors ［sodium sulfite（Na₂SO₃）/sodium bisulfite（NaHSO₃），85 mg·kg^－1·d^－1］ for 8 weeks； the pathomorphology of myocardial fibrosis of the rats in various groups was observed by Masson staining， and the myocardial collagen volume fractions of the rats in various groups were calculated， and the expression levels of relevant proteins in myocardial tissue of the rats in various groups were detected by Western blotting method. Results Compared with control group， the myocardial tissue of the rats in T2DM group showed morphology and structural disorders， the myocardial collagen fiber formation was significantly increased， the myocardial collagen volume fraction was significantly increased （P<0.01）， the expression levels of α-smooth muscle actin（α-SMA） and type Ⅲ collagen（Col Ⅲ），B-cell lymphoma-2（Bcl-2） associated X protein（Bax）， TGF-β1， Smad2， and Smad3 proteins were significantly increased （P<0.01）， and the expression level of Bcl-2 protein was significantly decreased （P<0.01）. Compared with T2DM group， the morphological structure of myocardial tissue of the rats in T2DM+SO₂ group was improved， the myocardial collagen fiber formation and the myocardial collagen volume fraction were significantly decreased（P<0.01）， the expression levels of α-SMA， Col Ⅲ， Bax， TGF-β1， Smad2， and Smad3 proteins were significantly decreased（P<0.01），and the expression level of Bcl-2 protein was significantly increased （P<0.01）. Compared with control group， there were no statistically significant differences in the above indexes of the rats in SO₂ group rats（P>0.05）. Conclusion SO₂ can alleviate myocardial fibrosis in the T2DM rats by inhibiting the expressions of pro-apoptosis-related proteins and TGF-β1/Smad2/3 pathway proteins.

Key words: Sulfur dioxide, Transforming growth factor-β1, Smad family member 2, Smad family mumber 3, Apoptosis, Myocardial fibrosis, Type 2 diabetes mellitus