Clock gene Bmal1 alleviate ischemia-reperfusion injury in transplanted kidney by regulate peroxisome proliferator activated receptor α/peroxisome proliferator activated receptor coactivator-1α pathway

Objective This study was to investigate the effect of clock gene Bmal1 on ischemia-reperfusion injury in transplant kidney (TK) and relationship with peroxisome proliferator activated receptor α (PPARα)/peroxisome proliferator activated receptor coactivator-1α (PGC-1α) pathway. Methods Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, TK group, Bmal1 short hairpin RNA (shRNA) group, Bmal1 shRNA+ fenofibrate group. Each group was given appropriate intervention and took specimens. The levels of serum creatinine (Cr) and urea nitrogen (BUN) were measured. The histopathological changes of kidneys in each group were estimated by hematoxylin and eosin (HE) staining. Western blotting was used to detect the expression of Bmal1, PPARα, PGC-1α, bcl-2/bax in kidney tissue. The amount of adenosine triphosphate (ATP) produced was determined by using colorimetric kit. SPSS 17.0 software was used for statistical analysis. The measurement data were expressed as mean±standard deviation. The comparison between two groups was analyzed with Student’s t test. The comparison among three or more groups was performed by one-way ANOVA test. Results Compared with the sham operation group (73.5±6.7, 8.2±0.7, 2.16±0.20, 3.15±0.29, 6.28±0.42, 2.09±0.22, 29.33±3.14), the serum Cr (211.0±17.4) and BUN levels (44.0±3.8) and renal tissue damage were increased (t=18.063, 22.695, P<0.05), while the expression of Bmal1 (1.63±0.17), PPARα (2.52±0.20), PGC-1α (4.65±0.37), bcl-2/bax (1.22±0.14) and ATP production (15.34±1.02)were decreased (t=4.946, 4.450, 7.133, 8.172, 10.380, P<0.05) in the TK group. Compared with the TK group, Bmal1 shRNA group showed increased Cr (307.0±28.9) and BUN (53.0±4.2) levels and renal tissue damage was increased (t=6.971, 3.892, P<0.05), but decreased expression of Bmal1 (1.30±0.11), PPARα (2.01±0.23), PGC-1α (3.86±0.20), bcl-2/bax (0.76±0.06) and ATP production (10.15±0.96) (t=3.992, 4.099, 4.601, 7.398, 9.076, P<0.05). Compared with Bmal1 shRNA group, the serum Cr (241.3±20.2) and BUN levels (47.0±4.5) and renal tissue damage were decreased (t=4.564, 2.388, P<0.05), while the expression of Bmal1 (1.55±0.10), PPARα (2.48±0.17), PGC-1α (4.36±0.25), bcl-2/bax (1.10±0.11) and ATP production (14.71±1.21) were increased (t=4.119, 4.025, 3.826, 6.647, 29.572, P<0.05) in Bmal1 shRNA+ fenofibrate group. Conclusion The clock gene Bmal1 protects against I/R injury in transplanted kidney via regulate PPARα/PGC-1α pathway.