Isoflurane preconditioning protects against renal ischemia/reperfusion injury in diabetes via activation of the Brg1/Nrf2/HO-1 signaling pathway

异氟烷预处理通过激活 Brg1/Nrf2/HO-1 信号通路预防糖尿病肾缺血/再灌注损伤

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作者:Daojing Gong, Ziqiang Dong, Xiaobo Chen, Hao Chen, Huihuang Lin

Conclusions

These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

Methods

Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined.

Purpose

To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms.

Results

Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane. Conclusions: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

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