G protein-coupled estrogen receptor protects renal ischemia-reperfusion injury by reducing endoplasmic reticulum stress apoptosis in rat kidney

To investigate the relationship between G protein-coupled estrogen receptor (GPER) and renal ischemia-reperfusion (I/R) injury. Twelve-week-old female rats were randomly divided into normal control group, ovariectomized (OVX) group, OVX + I/R group, OVX + I/R + vehicle group, OVX + I/R + E2 (estrogen intervention) group, OVX + I/R + G1 (GPER agonist intervention) group, OVX + I/R + G15 (GPER antagonist) + G1 group. The renal function of rats in each group after ischemia-reperfusion was detected. The transcriptomic profile of renal tissue in estrogen intervention group and ischemia-reperfusion group was analyzed by mRNA sequencing, and the differentially expressed genes (DEGs) were enriched in negative apoptosis regulation and other pathways. The expression of renal tissue myeloperoxidase (MPO) and endoplasmic reticulum stress apoptosis-related proteins and the apoptosis of renal tubular epithelial cells were observed. Compared with the OVX group, the serum creatinine (SCr) and blood urea nitrogen (BUN) in the OVX + I/R group were significantly increased ( P < 0.01), the Paller score was significantly increased ( P < 0.01), and the MPO level was significantly increased ( P < 0.01). The expression of GRP78, CHOP and Caspase-12 proteins in renal tubular epithelial cells was significantly increased ( P < 0.01), and TUNEL staining showed a significant increase in apoptotic renal tubular epithelial cells. Compared with OVX + I/R group, the serum creatinine (SCr) and blood urea nitrogen (BUN) of renal function in OVX + I/R + E2 group and OVX + I/R + G1 group were significantly decreased ( P < 0.01), the Paller score was significantly decreased ( P < 0.01), the MPO level was significantly decreased ( P < 0.01), the expression of GRP78, CHOP and Caspase-12 proteins was significantly decreased ( P < 0.01), and the apoptosis of renal tubular epithelial cells was significantly decreased ( P < 0.01). Activation of G protein-coupled estrogen receptor may attenuate renal I/R injury, which is associated with down-regulation of the endoplasmic reticulum stress-mediated apoptotic pathway.