α-硫辛酸对糖尿病大鼠心肌病保护作用

Protective effect of α-lipoic acid on diabetes cardiomyopathy in rats

目的探讨α-硫辛酸对糖尿病心肌病大鼠心肌损伤保护作用及其机制。方法 SD大鼠随机分为5组:对照组、糖尿病模型组、α-硫辛酸低、中、高剂量组。以60 mg/kg链脲佐菌素腹腔一次性注射建立大鼠糖尿病模型;α-硫辛酸低、中、高剂量组分别按15、30、60 mg/kg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 blot法测定心肌组织基质金属蛋白酶-9(MMP-9)、-2(MMP-2)和金属蛋白酶组织抑制因子-1(TIMP-1)蛋白表达。结果与对照组比较,糖尿病模型组大鼠血糖值/血清果糖胺含量明显升高(P<0.05),心肌组织中MMP-2、MMP-9和TIMP-1蛋白表达及MMP-9/TIMP-1比值明显增加(P<0.05);与糖尿病模型组比较,α-硫辛酸中剂量组血糖[(14.25±3.23)mmol/L]和血清果糖胺[(3.05±0.20)mmol/L]含量明显降低(P<0.05),左室舒张末压[(5.60±0.98)mmHg]明显降低(P<0.05),左心室收缩压[(127.55±5.45)mmHg]明显升高(P<0.05);α-硫辛酸中剂量组MMP-2、MMP-9、TIMP-1蛋白表达分别为62.26、76.78、72.87,明显减少(P<0.05)。结论α-硫辛酸对糖尿病大鼠心肌组织具有保护作用,其机制可能与细胞因子及细胞外基质组成异常有关。

Objective To explore protective effect of alpha-lipotic acid（ALA） on diabetes cardiomyopathy and its mechanism. Methods SD rats were randomly divided into normal control, diabetes model,low, moderate and high dose ALA treatment groups with a peritoneal injection of streptozotocin （STZ） of 60 mg/kg. The rats in ALA treatment groups were administrated by gavage with ALA at the dosages of 15,30, and 60 mg/kg a day for 12 weeks. The contents of blood sugar and serum fructosoamine were detected. Immunohistochemistry method and western blot method were used to determine matrix metalloproteinase-9 （ MMP-9 ）, metalloproteinase-2 （ MMP-2 ）, and tissue inhibitors of matrix metalloproteinase-1 metal protease organization inhibitory factor-1 （ TIMP-1 ） in myocardial tissue of the rats. Results Compared with those of the control group（4. 62 ± 1.03,3.2 ±0. 19） ,fasting blood glucose and serum fructosamine of the diabetic rats （25.45 ±3.24, 4.43 ± 0. 62 ） were significantly up-regulated （ P 〈 0. 05 ）. Cardiac function test showed that left ventricular end-diastolic pressure （LVEDP） increased and left ventricular systolic pressure （ LVSP）, ±dp/dtmax declined significantly in diabetecs rats compared with those of control rats （ P 〈 0. 05 for all） and the protein expressions of MMP-2 （ 68.9 ± 4. 35 ）, MMP-9 （87. 38 ± 11.10） ,TIMP-1 （81.82 ±9. 61 ） ,and MMP-9/TIMP-1 （ 1.07 ± 0. 06） were also significantly up-regulated in the diabetic rats （P 〈 0. 05 for all）. Compared with the diabetic group, fasting blood glucose and serum fructosamine of the ALA treated rats were significantly decreased （ P 〈 0. 05 for all） and LVEDP （ 5.60± 0. 98 mmHg ） deccreased significantly （P 〈0.05） and LVSP（ 127.55 ±5.45 mmHg） elevated （P 〈 0.05）. The protein expression of MMP-2（62. 26） ,MMP-9 （ 76. 78 ）, TIMP-1 （ 72. 87 ） and MMP-9/TIMP-1 （ 1.03 ） of ALA treated rats were significantly decreased compared to those of the diabetic model rats （ P 〈 0.05 for all）. Conclusion ALA has protective effect on diabetic cardiomyopathy through regulating MMPs and TIMP-1.