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| Role of angiotensin-(1-7)/angiotensin-Ⅱin kidney ischemia-reperfusion injury by regulating Nrf2/HO-1 pathway in diabetic rats |
| SUN Qian ZENG Cheng DUAN Weina MENG Qingtao XIA Zhongyuan |
| Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430061, China |
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Abstract Objective To investigate the role of angiotensin-(1-7）/angiotensin-Ⅱ[Ang-(1-7）/Ang-Ⅱ] in kidney ischemia-reperfusion injury by regulating NF-E2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in diabetic rats. Methods Sixty male SD rats were randomly divided into four groups: Sham group, kidney ischemia-reperfusion group (IR group), diabetic group (DS group), diabetic+KIR group (DIR group), with 15 rats in each group. Kidney ischemia reperfusion model of STZ-diabetic rat model was used. After 24h reperfusion, blood urea nitrogen (BUN), creatinine (Cr), and neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were measured. Renal histology was observed and evaluated. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels in renal tissues were detected. Western blot were used to observe the expression levels of Ang-(1-7), Ang-Ⅱ and Nrf2, HO-1 in renal tissues. Results Expressions of Ang-(1-7) in DS group were higher than those in sham group (P < 0.05), the expressions of Ang-(1-7) in IR group were lower than those in sham group (P < 0.05), the expressions of Ang-(1-7) in DIR group were much lower than those in IR group (P < 0.05). The expressions of Ang-Ⅱ in IR and DS group were higher than those in Sham group (P < 0.05), the expressions of Ang-Ⅱ in DIR group were higher than those in IR and DS group (P < 0.05). The expressions of Nrf2 and HO-1 in IR and DS group were higher than those in sham group (P < 0.05), the expressions of Nrf2 and HO-1 in DIR group were lower than those in IR and DS group (P < 0.05). Compare with Sham group, BUN, Cr and NGAL in serum and MDA levels in the renal tissues were increased, and SOD levels were decreased in IR and DS group (P < 0.05). Compare with IR and DS group, BUN, Cr and NGAL in serum and MDA levels in the renal tissues were further increased (P < 0.05), and SOD levels were further decreased in DIR group (P < 0.05). Conclusion Ischemia reperfusion might inhibit the Ang-(1-7), activate the Ang-Ⅱ and down regulate the anti-oxidative stress of Nrf2/HO-1 pathway, resulting in the damage of diabetic kidney.
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