小檗碱抑制糖尿病大鼠心肌纤维化

Berberine inhibits cardiac fibrosis of diabetic rats

目的观察小檗碱对糖尿病大鼠血清转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)、心肌组织1型胶原蛋白(Col1)和Col3的表达,探讨其对糖尿病心肌纤维化的影响。方法采用腹腔注射链脲佐菌素(STZ)法复制糖尿病大鼠模型,将造模成功的43只大鼠随机分为模型组、(50、100、150)mg/(kg·d)小檗碱组,灌胃给药12周;另设正常对照组和140 mg/(kg·d)二甲双胍组。用药结束后,检测大鼠空腹血糖、左心室收缩压(LVSP)和左心室舒张末压(LVEDP)水平,取大鼠心脏,计算心脏质量指数;ELISA测定血清TGF-β1、CTGF的含量;心肌组织Masson染色观察心肌的纤维化程度;Western blot法检测心肌组织Col1、Col3的表达水平。结果与正常组相比,模型组大鼠空腹血糖水平、心脏质量指数、LVSP水平、LVEDP绝对值、TGF-β1、CTGF、心肌纤维化程度以及Col1、Col3的水平均明显升高;与模型组相比,(100、150)mg/(kg·d)小檗碱组和二甲双胍组大鼠空腹血糖水平、心脏质量指数、LVSP水平、LVEDP绝对值、TGF-β1、CTGF、心肌纤维化程度以及Col1、Col3的水平均明显降低。结论小檗碱可降低糖尿病大鼠TGF-β1、CTGF的含量,减少Col1、Col3在心肌间质沉积,对糖尿病大鼠的心肌纤维化有一定的抑制作用。

Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1（ TGF-β1）,connective tissue growth factor（ CTGF）,collagen type 1（ Col1） and collagen type 3（ Col3） in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci（ STZ）. Forty-three diabetic rats were randomly divided into diabetic model group（ n = 9）,berberine treated groups of different doses [50,100,150 mg /（ kg·d）,gavage administration for 12 weeks;n = 9,9,8 respectively],and metformin group as positive control（ n = 8）; other 8 normal rats served as a negative control group. After the last administration,fasting blood glucose,left ventricular systolic pressure（ LVSP） and left ventricular end diastolic pressure（ LVEDP） were measured; rats＇ heart were taken to calculate the heart mass index（ HMI）; ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining;collagen volume fraction（ CVF） was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group,the fasting blood glucose,LVSP,LVEDP absolute value,HMI,the degree of cardiac fibrosis,the expressions of TGF-β1,CTGF,Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg /（ kg·d）.Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.