Abstract: Objective To observe the protective effect of peroxisome proliferator-activated receptor γ (PPAR-γ) overexpression against renal ischemia-reperfusion (RI/ R) injury in rats, and explore its mechanism. Methods A total of 40 SD rats were randomly divided into 4 groups as follows: the control group, the RI/ R model group, the RI/ R + LV group and the RI/ R + PPAR-γ group, 10 cases in each group. The blood flow of bilateral renal artery was blocked by surgery to construct the RI/ R injury model. Before reperfusionrecovery, rats in the RI/ R + PPAR-γ group were injected with PPAR-γ recombinant lentiviral vector through the tail vein, rats in the RI/ R + LV group were injected with the lentiviral vector containing empty plasmid, while rats in the RI/ R model group wereinjected withnormal saline. After reperfusion, pathological changes in renal tissues were observed by HE staining and Masson staining. The levels of urine protein, serum creatinine (Scr) and blood urea nitrogen (BUN) were measuredby automatic biochemical analyzer. The levels of tumor necrosis factor-α (TNF-α) and interleukin 6 ( IL-6) in serum and renal tissues were determinedby ELISA. The expression level of PPAR-γ mRNA in renal tissues was detected by RT-PCR. The expression levels of PPAR-γ, transforming growth factor β (TGF-β), α-smooth muscle actin ( α-SMA), fibronectin ( FN) and apoptosis-related proteins ( Bax, Bcl-2, caspase-3, Cleaved caspase-3, caspase-9, Cleaved caspase-9) in renal tissues were detectedby Western blotting. Results Compared with the control group, levels of PPAR-γ mRNA and protein were decreased in the RI/ R model group (P< 0. 05), while levels of urine protein, Scr, BUN, TNF-α, IL-6, Bax / Bcl-2, cleaved caspase-3 / caspase-3, cleaved caspase-9 / caspase-9, TGF-β, α-SMA and FN were increased (P< 0. 05). Compared with the RI/ R model group, levels of PPAR-γ mRNA and protein were increased in the RI/ R + PPAR-γ group (P< 0. 05), while levels of urine protein, Scr, BUN, TNF-α, IL-6, Bax / Bcl-2, cleaved caspase-3 / caspase-3, cleaved caspase-9 / caspase-9, TGF-β, α-SMA and FN were decreased (P < 0. 05). Conclusion Overexpression of PPAR-γ can improve renal fibrosis by reducing the release of pro-inflammatory cytokines, thus decreasing RI/ R injury.

Key words: renal ischemia-reperfusion, injury, rats, peroxisome proliferator activated receptor γ, inflammation, renal fibrosis