关键词: 糖尿病, 大鼠, 肝脏, 氧化应激, ACE2

Abstract: This study aimed to investigate possible protective effect and mechanism of ACE2 against diabetes-induced liver oxidative stress injury in rats. A total of 24 male healthy SD rats were used in this study. Eight rats without any treatment were used as negative control, and 16 others were administrated with STZ solution (60 mg/kg) via the ip route to induce diabetic hepatic oxidative stress injury model and then divided into 2 groups: diabetes group and insulin (3.7 × 10-8 mol/d) treatment group. After 30 days of administration, all the rats were sacrificed and blood and hepatic tissues were harvested to measure the content of AGEs in serum, the contents of MDA, H2O2 and the activity of SOD and GSH-Px in hepatic tissues. The contents of AngⅡ and Ang1-7 were also investigated as well as the activities of ACE and ACE2 in hepatic tissues. Results showed that the average fasting blood glucose level in normal control group was (5.39 ± 0.30) mmol/L, compared to (28.24 ± 2.51) mmol/L (much higher than the hyperglycemia index of 16.6 mmol/L) in diabetes group. The average fasting blood glucose level of measurements at intervals of 5 days during the administration period was significantly reduced to (11.18 ± 1.26) mmol/L, which, however, was still significantly higher than normal control group (P ＜ 0.05), and reached a level lower than 10.0 mmol/L and even close to the normal level at the end of the administration period. The serum content of AGEs in diabetes control group was significantly higher than that in normal control group and insulin treatment group (P ＜ 0.05). Compared with normal control group and insulin treatment group, there were significant increases in the serum content of AngⅡ, the activity of ACE and the contents of MDA and H2O2 in hepatic tissues of diabetes group but reductions in the activities of SOD, GSH-Px and ACE2 and the content of Ang1-7. In summary, the liver of the diabetes rats had a local increase in AngⅡ content but a decrease in ACE2 content and underwent oxidative stress. Following insulin treatment, the enhancement in ACE2 activity resulted in degradation of AngⅡ, thus relieving the oxidative stress of liver. These results suggest that ACE2 might have some protective effect against hepatic oxidative stress in diabetes rats and the mechanism appears to be related to the enhanced degradation of AngⅡ.

Key words: diabetes, rats, liver, oxidative stress, ACE2