To explore the protective effect of protein kinase Cβ (PKCβ) inhibitor LY333531 in diabetic rats with contrast-induced acute kidney injury and its mechanism.

Totally 40 rats were randomly divided into a control group (C group), a diabetic group (D group), a diabetes with contrast-induced nephropathy group (DC group) and a diabetes with Y333531 and contrast-induced nephropathy group (DCL group), 10 rats in each group. The rats in the D, DC and DCL groups were injected intraperitoneally with 2% streptozotocin (60 mg / kg) to induce a diabetes model. Then the rats in the DCL group were pretreated with LY333531 (10 mg·kg^-1·d^-1) by intragastric administration for 14 d; the rats in the DC and DCL groups were injected with 76% diatrizoate (10 mL / kg) by tail vein to establish a model of contrast-induced nephropathy. The pathological changes in kidney were observed by hematoxylin-eosin (HE) staining. The levels of blood glucose, serum creatinine, urine microalbumin (mAlb) and urine N-acetyl-β-D-glucosidase (NAG) were detected. The messenger RNA (mRNA) levels of transforming growth factor beta1 (TGFβ1), Smad3, Smad7, Bax, Caspase3 and Bcl2 were examined by real-time fluorescence quantitative PCR. The protein levels of TGFβ1, Bax, Caspase3 and Bcl2 were detected by Western-blotting, as well as the phospho-PKCβ (pPKCβ) / PKCβ and phospho-p38 (p-p38) / p38.

According to HE, the glomeruli and renal tubules in the group C were structurally normal; the glomeruli and renal tubules in the group D were relatively structurally complete with few inflammatory cells around the interstitium; the epithelial cells of renal tubules in the DC group were exfoliated and the inflammatory cells obviously infiltrated around renal tubules; in the DCL group, the degree of epithelial cell shedding in renal tubules was significantly reduced, and a small amount of inflammatory cells infiltrated in the interstitium around renal tubules and glomeruli. The blood glucose, serum creatinine, urine mAlb, urine NAG, TGFβ1 protein and its mRNA, Smad3 mRNA, Smad7 mRNA, Bax protein and its mRNA, Caspase3 protein and its mRNA, Bcl2 protein and its mRNA, pPKCβ / PKCβ and p-p38 / p38 all showed significant differences among the four groups (F = 67.976, P < 0.001; F = 27.155, P < 0.001; F = 41.201, P < 0.001; F = 59.635, P < 0.001; F = 21.073, P < 0.001; F = 28.365, P < 0.001; F = 15.215, P < 0.001; F = 36.273, P < 0.001; F = 14.489, P < 0.001; F = 23.172, P < 0.001; F = 17.103, P < 0.001; F = 29.916, P < 0.001; F = 12.026, P < 0.001; F = 13.368, P < 0.001; F = 6.126, P = 0.002; F = 6.434, P = 0.002). Further pairwise comparison revealed that the levels of blood glucose in the D, DC and DCL groups were significantly higher than those in the C group (all P < 0.05). As compared with the DC group, the serum creatinine, urine mAlb, urine NAG, TGFβ1 protein and its mRNA, Smad3 mRNA, Bax protein and its mRNA, Caspase3 protein and its mRNA, pPKCβ / PKCβ and p-p38 / p38 decreased markedly, while the Smad7 mRNA, Bcl2 protein and its mRNA increased obviously in the DCL group (all P < 0.05).

The PKCβ inhibitor LY333531 can improve contrast-induced acute kidney injury in diabetic rats by inhibiting the PKCβ-TGFβ-p38-Caspase3 pathway.