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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 the protective effect and mechanism of α-lipoic acid on hepatic fibrosis in diabetic liver disease rats. Methods SD rats were randomly divided into control group (n = 10), diabetic liver disease group (n = 8, intraperitoneal injection of streptozotocin 60 mg / kg + subcutaneous injection of 40% carbon tetrachloride 0.2 mL / - lipoic acid low, medium and high dose group (n = 9, intragastric administration of 15, 30, 60 mg / kg α-lipoic acid, continuous 12 weeks), blood glucose and liver malondialdehyde, glutathione (GSH-Px), superoxide dismutase (SOD), and the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in liver tissue. Results Compared with the control group, the levels of blood glucose ([(25.45 ± 3.24) mmol / L] and malondialdehyde (11.90 ± 3.38 μg / mg.pro) in diabetic liver disease group increased and the activities of SOD and GSH-Px (38.45 ± 6.73) and (19.54 ± 2.24) μg / mg.pro] respectively, and the expressions of MMP-9 and TIMP-1 and the ratio of MMP-9 / TIMP- Compared with the control group, blood glucose [(14.25 ± 3.23) mmol / L] and MDA content [(8.05 ± 2.13) μg / mg.pro] in the middle dose of α-lipoic acid group were decreased and the activities of SOD and GSH-Px (46.95 ± 6.13) and (25.14 ± 3.23) μg / mg.pro], respectively (P <0.01). The expressions of MMP-9 and TIMP-1 and the ratio of MMP- <0.01). Conclusion α-lipoic acid has a protective effect on liver tissue of diabetic liver disease rats, and its mechanism may be related to anti-oxidation process.