SO2对2型糖尿病大鼠心肌纤维化的影响及与MST1/LATS1的关系

目的 探讨外源性气体信号分子二氧化硫(SO₂)在2型糖尿病(T2DM)大鼠心肌纤维化中的作用，并观察其对促凋亡蛋白及MST1/LATS1通路蛋白表达的影响。方法 40只雄性SD大鼠被随机分为对照组、糖尿病组、糖尿病+SO₂组、SO₂组，其中糖尿病组和糖尿病+SO₂组使用链脲佐菌素(STZ)腹腔内注射复制糖尿病大鼠模型，当血糖≥16.7 mmol/L时表示糖尿病模型复制成功，随后以高糖高脂饲料进行喂养。对照组和SO₂组注射等量柠檬酸-柠檬酸钠溶液，之后糖尿病+SO₂组和SO₂组以外源性SO₂供体腹腔内注射持续4周。对大鼠心肌组织进行Masson染色，观察心肌胶原纤维形成情况；透射电镜观察心肌超微结构；TUNEL染色观察心肌组织细胞凋亡情况；Western blotting检测心肌组织CollagenⅠ、CollagenⅢ、MST1、LATS1、Cleaved-Caspase-3、Cleaved-Caspase-9蛋...

The impact of SO2 on myocardial fibrosis and its relationship with MST1/LATS1 in rat models of type 2 diabetes mellitus

Objective To investigate the impact of exogenous gaseous signaling molecule sulfur dioxide (SO₂) on myocardial fibrosis in rat models of type 2 diabetes mellitus (T2DM), and to observe its effects on expressions of pro-apoptotic proteins and proteins associated with the MST1/LATS1 pathway.Methods Forty male SD rats were randomly divided into the control group, diabetes mellitus group, diabetes mellitus + SO₂ group, and SO₂ group. For rats in the diabetes mellitus group and the diabetes mellitus + SO₂ group, diabetes mellitus was induced by intraperitoneal injection of streptozotocin (STZ) and confirmed by the blood glucose concentration ≥ 16.7 mmol/L. After successful model establishment, rats were fed with a high-sugar and high-fat diet. The rats in the control group and the SO₂ group were injected with an equal volume of citric acid-sodium citrate solution. Subsequently, the rats in the diabetes mellitus + SO₂ group and the SO₂ group were intraperitoneally injected with exogenous SO₂ for 4 weeks. Myocardial tissues from the rats were subjected to various analyses, including Masson staining to assess collagen fiber formation, transmission electron microscopy to observe myocardial ultrastructure, TUNEL staining to evaluate apoptosis, and Western blotting to measure protein expression levels of collagen I, collagen III, MST1, LATS1, cleaved Caspase-3, and cleaved Caspase-9.Results In comparison to the control group, the diabetes mellitus group exhibited larger positive areas on Masson staining (P < 0.05). The positive areas on Masson staining in the diabetes mellitus + SO₂ group were smaller than those in the diabetes mellitus group (P < 0.05). There was no difference in the positive areas on Masson staining between the control group and the SO₂ group (P > 0.05). The relative protein expression levels of collagen I and collagen III in the diabetes mellitus group were higher than those in the control group (P < 0.05), while they were lower in the diabetes mellitus + SO₂ group than those in the diabetes mellitus group (P < 0.05). There was no difference in relative protein expression levels of collagen I and collagen III between the control group and the SO₂ group (P > 0.05). The apoptosis rate of cardiomyocytes in the diabetes mellitus group was higher than that in the control group (P < 0.05), while that in the diabetes mellitus + SO₂ group was lower compared with the diabetes mellitus group (P < 0.05). There was no difference in the apoptosis rate of cardiomyocytes between the control group and the SO₂ group (P > 0.05). The relative protein expression levels of cleaved Caspase-3, cleaved Caspase-9, MST1 and LATS1 in the myocardial tissues of the diabetes mellitus + SO₂ group were lower than those of the diabetes mellitus group (P < 0.05). There was no difference in the relative protein expression levels of cleaved Caspase-3, cleaved Caspase-9, MST1 and LATS1 between the control group and the SO₂ group (P > 0.05).Conclusions SO₂ regulates the expressions of pro-apoptotic proteins and proteins associated with the MST1/LATS1 pathway in myocardial tissues of rat models of T2DM, and exhibits a correlation with the amelioration of myocardial fibrosis.