α-硫辛酸对糖尿病大鼠肝脏损伤保护作用

Protective effect of α-lipoic acid on liver injury among diabetes mellitus rats

目的探讨α-硫辛酸对糖尿病肝病大鼠肝纤维化的保护作用及其机制。方法 SD大鼠随机分为对照组(n=10)、糖尿病肝病组(n=8,腹腔注射链脲佐菌素60 mg/kg+皮下注射40%四氯化碳0.2 mL/100 g)及α-硫辛酸低、中、高剂量组(n=9,灌胃给予15、30、60 mg/kgα-硫辛酸,连续12周),检测血糖和肝组织中丙二醛、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)水平、肝组织中基质金属蛋白酶9(MMP-9)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,糖尿病肝病组大鼠血糖[(25.45±3.24)mmol/L]和丙二醛[(11.90±3.38)μg/mg.pro]含量均升高,SOD、GSH-Px活性[(38.45±6.73)、(19.54±2.24)μg/mg.pro]均降低,MMP-9和TIMP-1蛋白表达量及MMP-9/TIMP-1比值均降低(P<0.01);与糖尿病肝病组比较,α-硫辛酸中剂量组大鼠血糖[(14.25±3.23)mmol/L]及丙二醛含量[(8.05±2.13)μg/mg.pro]均降低,SOD、GSH-Px活性[(46.95±6.13)、(25.14±3.23)μg/mg.pro]均升高(P<0.01),MMP-9和TIMP-1蛋白表达量及MMP-9/TIMP-1比值均升高(P<0.01)。结论α-硫辛酸对糖尿病肝病大鼠肝脏组织具有保护作用,其机制可能与抗氧化过程有关。

Objective To investigate protective effect and mechanism of α-lipoic acid on liver disease and hepatic fibrosis in diabetic rats. Methods The Sprague-Dawley rats were randomly divided into 5 groups：normal control group （n = 10） ,model group of diabetic liver disease induced by streptozotocin （60 mg/kg） intraperitoneal injection ＋ tetrachloride carbon （ n = 8 ）, low-dose α-lipoic acid group （ 15 mg/kg, d intragastirc administration for 12 weeks, n = 9 ）, medium-dose α-lipoic acid group（30 mg/kg, d intragastirc administration for 12 weeks, n = 9 ）, and high-dose α-lipoic acid group（60 mg/kg.d intragastirc administration for 12 weeks, n = 9 ）. Levels of malondialdehyde, glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD）, and blood glucose in blood and liver tissue of the rats were measured. Expression of matrix metalloproteinase 9 （MMP-9） and tissue inhibitor of metalloproteinase factor-1 （TIMP-1） protein expression were determined with immunohistochemistry and western blot. Results Compared with the normal control group, blood glucose（25.45 ± 3.24 retool/L） and malondialdehyde （ 11.90 ± 3.38 ug/mg . pro） were increased, while SOD （38.45 ± 6. 73 mmol/L）, GSH-Px （ 19. 54 ± 2. 24 mmol/L）, MMP-9, TIMP-1, and MMP-9/TIMP-1 were reduced （P 〈0. 01 for all）. Compared with the model group, blood glucose （ 14. 25 ± 3.23 mmol/L） and malondialdehyde （8.05 ±2. 13 mmol/L） of medium-dose α -lipoic acid group were reduced （ P 〈 0. 01 ）, and SOD （ 46. 95 ± 6. 13 mmol/L） ,GSH （ 25.14 ± 3.23 mmol/L）, MMP-9, TIMP-1, and MMP-9/TIMP-1 were increased （ P 〈 0. 01 for all）. Conclusion The study shows that a-lipoic acid has protective effect on liver tissue of diebetic rat. The mechanism probably relates to the reduce of oxide stress, attenuation of extracellular matrix, and inhibition of liver fibrosis.