To investigate the possible role and underlying mechanism of succinate receptor 1 (SUCNR1) in kidney ischemia-reperfusion injury (IRI).

Forty male C57 mice weighing 20-25 g with SPF grade were divided into 8 groups: sham-operated group, sham-operated+ succinate group, sham-operated+ IgG group, sham-operated+ SUCNR1 antibody group, IRI group, IRI+ IgG group, IRI+ succinate group, and IRI+ SUCNR1 antibody group. After the successful establishment of the IRI model, kidney function and cytokines level were measured from the serum, while the mice kidney tissues were obtained for pathological and histological staining as well as SUCNR1 mRNA and protein expression analysis. Measurement data between groups were analyzed by independent Student′s t-test. One-way analysis of variance was used for comparison among multiple groups, and that between groups with P<0.05 denoted statistical significance.

Serum succinate levels in the sham-operated group and IRI group were (28.74±3.14) and (52.60±4.66)μmol/L, respectively, with statistically significant difference (t=-9.494, P<0.05); the relative levels of SUCNR1 mRNA in the sham-operated group and IRI group were (1.00±0.14) and (3.65±1.05), respectively, with statistically significant difference (t=-5.567, P<0.05); the relative expression levels of SUCNR1 protein in the sham-operated group and IRI group were (0.16±0.04) and (0.63±0.06), respectively, and the difference was statistically significant (t=-14.574, P<0.05). The differences in serum creatinine and urea nitrogen in mice in the sham-operated group, sham-operated+ succinate group, IRI group and IRI+ succinate group were statistically significant (F=176.15 and 131.05, all P<0.05). Renal tubular injury, interstitial dilatation and edema, and inflammatory cell infiltration were observed in the IRI group compared to the sham-operated group, which were aggravated in IRI+ succinate group. The level of apoptosis in the renal tissues of mice in IRI+ succinate group was significantly increased compared with that in the IRI group. The differences in serum IL-6 and TNF-α levels in mice in the sham-operated group, sham-operated+ succinate group, IRI group, and IRI+ succinate group were statistically significant (F=256.25 and 268.99, all P<0.05). The differences in serum creatinine and urea nitrogen levels in the sham-operated+ IgG group, sham-operated+ SUCNR1 antibody group, IRI+ IgG group, and IRI+ SUCNR1 antibody group were statistically significant (F=54.13 and 84.52, all P<0.05). Compared with the IRI+ IgG group, renal tubular injury, interstitial dilatation and edema, and inflammatory cell infiltration were significantly reduced in IRI+ SUCNR1 antibody group. Compared with the IRI+ IgG group, the apoptosis level in mice kidney tissue was significantly reduced in IRI+ SUCNR1 antibody group. The differences in IL-6 and TNF-α in the serum of mice in the sham-operated, sham-operated+ SUCNR1 antibody, IRI, and IRI+ SUCNR1 antibody groups were statistically significant (F=123.31 and 268.144, all P<0.05).

SUCNR1 may aggravate mice renal IRI by promoting renal inflammatory response and apoptosis.