The intervention effect of Schisandrin B on cisplatin induced acute kidney injury in mice / 中国中西医结合急救杂志

ABSTRACT

Objective To observe the intervention effect of Schisandrin B (Sch B) on cisplatin induced acute kidney injury (AKI) in mice and its possible mechanism.Methods Twenty-five BALB/c mice were randomly divided into blank control group, model group, low and high dose of Sch B intervention groups and Sch B control group. Olive oil with Sch B was administered by gavage at the dose of 20 mg/kg or 100 mg/kg for low and high dose of Sch B intervention groups respectively; olive oil with Sch B 100 mg/kg was applied by gavage to the Sch B control group; the same volume of olive oil was perfused into the gastric cavity in the blank control group and model group; the above measures in various groups were consecutively used for 5 days. On the 3rd day of the experiment, AKI mice model was established by intraperitoneal injection of cisplatin (20 mg/kg) once and the same measure was given to the low and high dose of Sch B intervention groups; 1 mL/kg normal saline was injected into the peritoneal cavity in the bland control group and Sch B control group. At the end of the experiment, the serum creatinine (SCr) level was determined; apoptosis of renal tubular epithelial cells were detected by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay; the morphological changes of renal tubular epithelial cells were observed by hematoxylin eosin (HE) staining, and renal tubular injury score was evaluated; p53 protein content in the kidney tissue was measured by immunohistochemical analysis; furthermore, expressional level of p53 protein in renal tissue was tested by Western Blot.Results Compared with the blank control group, the level of SCr (μmol/L 86.77±10.97 vs. 14.37±0.81), renal tubular injury score (9.67±1.20 vs. 1.00±0.45), the count of apoptotic renal tubular epithelial cells (cells/200 power field 20.00±2.13 vs. 2.30±0.40) in the model group were all increased (P < 0.05 orP < 0.01), and p53 protein content (cells/400 power field 13.40±2.66 vs. 57.30±3.82), and the expression of p53 protein [absorbency (A value) ratio 0.79±0.09 vs. 1.42±0.09] in model group were decreased (bothP < 0.01). Compared with the model group, in the low and high dose Sch B intervented groups, the level of SCr (μmol/L 21.98±5.52 and 37.45±5.04), renal tubular injury score (5.67±0.76 and 6.17±0.65), the count of apoptotic renal tubular epithelial cells (cells/200 power field 10.60±1.05 and 11.60±1.45) were all reduced (allP < 0.01), p53 protein content (cells/400 power field 42.40±3.67 and 45.90±2.31) and the expression of p53 protein (A value ratio 1.36±0.16 and 1.25±0.11) were increased (bothP < 0.01). HE staining showed the pathological changes of renal tubules, such as renal tubular epithelial cellular fusion, vacuolization, cast formation, and tubular lumen constriction/dilation in model group; the pathological changes in kidney tissues observed in low and high dose Sch B intervention groups were milder than those in model group.Conclusion Sch B plays a beneficial role in the cisplatin induced AKI in mice, and its protective effect might be mediated by decreasing SCr, regulating p53 protein expression level and inhibiting the apoptosis of renal tubular epithelial cells.