Protective effect of diminazene on kidney injury of limb ischemiareperfusion model mice and its mechanism / 吉林大学学报(医学版)

ABSTRACT

Objective: To detect the levels of angioteinsin II (Ang II) and angioteinsin (1-7) [Ang (1-7)] and the expression levels of angiotensin II type-1 receptor (AT1R) and Mas receptor (MasR) proteins in kidney tissue of the limb ischemia-reperfusion (LIR) mice pre-treated with the angiotensin coverting enzyme 2 (ACE2) activator diminazene (DIZE), and to explore the protective effect of DIZE on the kidney injury of the LIR mice. Methods: Eighteen male ICR mice aged 8 weeks were divided into control group, LIR group and LIR+DIZE group. The mice in model group and LIR+DIZE group were subjected to 2 h of ischemia and 4 h of reperfusion to establish the LIR models. The mice in LIR + DIZE group were pre-treated with 10 mg · kg-1 · d-1 DIZE for 14 d by subcutaneous injection before LIR. The histological technique was used to observe the morphology of kidney tissue of the mice and the pathological injury was evaluated. Chemical colorimetry was performed to determine the levels of serum urea and serum creatinine (Scr) of the mice. Enzyme linked immunosorbent assay (ELISA) was used to determine the Ang II and Ang (1-7) levels in kidney tissue of the mice. Western blotting method was used to measure the expression levels of AT1R and MasR proteins in kidney tissue of the mice. Results: Compared with control group, the pathological changes such as inflammatory cell infiltration and epithelial cell degeneration were found in kidney tissue of the mice in LIR group, and the kindey injury score was obviously increased (P<0. 05); compared with LIR group, the kidney injury performance in the kidey tissue of the mice in LIR + DIZE group was alleviated and the kidney injury score was decreased significantly (P<0. 05). Compared with control group, the levels of serum urea and Scr of the mice in LIR group were significantly increased (P<0. 05); compared with LIR group, the levels of serum urea and Scr of the mice in LIR + DIZE group were significantly decreased (P<0. 05). Compared with control group, the Ang II, Ang (1-7) levels and the ratio of Ang II/Ang (1-7) of the mice in LIR group were significantly increased (P<0. 05); compared with LIR group, the Ang II level of the mice in LIR+DIZE group was markedly decreased (P<0. 05), the Ang (1-7) level was significantly increased (P<0. 05)), and the ratio of Ang II/Ang (1-7) was decreased (P<0.05). Compared with control group, the expression level of AT1R protein in kidney tissue of the mice in LIR group was significantly decreased (P<0.05), the expression of MasR protein was significantly increased (P<0. 05), and the ATlR/MasR ratio was decreased (P<0.05). Compared with LIR group, the AT1R and MasR protein expression levels in kidney tissue of the mice in LIR + DIZE group were significantly increased (P < 0.05), and the ATlR/MasR ratio was also increased (P < 0.05). Conclusion: The imbalance of Ang II/Ang (1-7) and AT1R/Mas expressions in kidney tissue of the mice may be involved in kidney injury after LIR of the mice. ACE2 activitor DIZE may play a protective role in the kidney by improving the imbalance of Ang II/Ang (1-7) and ATlR/MasR expressions.