摘要
目的探讨水飞蓟素对糖尿病心肌病大鼠心肌损伤的保护作用及机制。方法 SD大鼠随机分为5组:正常对照组、模型组及水飞蓟素低、中、高剂量组。模型组及水飞蓟素治疗组采用链脲佐菌素以60 mg/kg于左下腹腔一次性注射建立大鼠糖尿病模型。水飞蓟素低、中、高剂量组分别以50、100、200 mg/(kg.d)水飞蓟素灌胃12周。检测血糖和血清果糖胺,心功能状态;免疫组织化学法和Western Blotting法测定心肌组织转化生长因子β1、基质金属蛋白酶9和组织型金属蛋白酶抑制剂1的蛋白表达。结果与正常对照组相比,模型组大鼠血糖和血清果糖胺含量明显增高(P<0.01);心功能检查左心室舒张期末压显著升高(P<0.01),左心室收缩压、左心室内压最大上升和下降速率均显著降低(P<0.01);心肌组织中转化生长因子β1、基质金属蛋白酶9和组织型金属蛋白酶抑制剂1蛋白表达含量及基质金属蛋白酶9/组织型金属蛋白酶抑制剂1比值均显著增加(P<0.01)。与模型组比较,水飞蓟素各治疗组血糖和血清果糖胺含量显著降低(P<0.01);心功能检查左心室舒张期末压显著降低(P<0.01),左心室收缩压、左心室内压最大上升和下降速率均显著升高(P<0.01);转化生长因子β1、基质金属蛋白酶9和组织型金属蛋白酶抑制剂1的蛋白表达及基质金属蛋白酶9/组织型金属蛋白酶抑制剂1比值均显著减少,尤以高剂量组改善最为明显(P<0.01)。结论水飞蓟素对糖尿病大鼠心肌组织具有保护作用,其机制可能为调节参与糖尿病心肌病发病中的细胞因子及细胞外基质组成有关,其中转化生长因子β1、基质金属蛋白酶9和组织型金属蛋白酶抑制剂1在糖尿病心肌病变发生、发展中具有重要作用。
Aim To investigate the protective effects of silymarin on cardiac muscle in diabetic rats and explore its therapeutic mechanism. Methods The SD rats were randomly divided into five groups： the normal control group,the diabetic model group,the low,middle,high doses of silymarin therapy group.The diabetic model was established following intraperitoneal injection of streptozocin with 60 mg/kg.Silymarin of 50,100,200 mg/kg was given to the low,middle,high doses of drug therapy group for 12 weeks.Fasting blood glucose,serum fructosamine and heart function were respectively measured.Semiquantitative expressions of transforming growing factor-β1（TGF-β1）,matrix metalloproteinases-9（MMP-9） and tissue inhibitors of matrix metalloproteinase-1（TIMP-1） protein were determined by immunohistochemistry and Western Blotting. Results Compared with the normal control group,fasting blood glucose,serum fructosamine of the diabetic rats were significantly upregulated（P〈0.01）.Left ventricular end diastolic pressure（LVEDP） were much higher（P〈0.01）,and left ventricular systolic pressure（LVSP）,±dp/dtmax were declined significantly（P〈0.01） by heart function measured.The protein expression of TGF-β1,MMP-9,TIMP-1 and MMP-9/TIMP-1 were significantly upregulated（P〈0.01）.Compared with the diabetic group,fasting blood glucose and serum fructosamine of silymarin therapy groups were significantly decreased（P〈0.01）.LVEDP were significantly declined（P〈0.01）,and LVSP,±dp/dtmax were elevated（P〈0.01） by heart function measured.The protein expression of TGF-β1,MMP-9,TIMP-1 and MMP-9/TIMP-1were significantly decreased（P〈0.01）. Conclusion The expression of TGF-β1,MMP-9,TIMP-1 are related to diabetic cardiomyopathy（DCM）,Silymarin has protective effect on DCM through affecting the changes of indexes mentioned above.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2010年第8期625-629,共5页
Chinese Journal of Arteriosclerosis
