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.

Objective To explore the protective effects of schisandrin B (Sch B) on hypoxia injury induced by cobaltous chloride (CoCl2) in human proximal renal tubular epithelial (HK-2) cells, and the possible mechanism thereof. Methods HK-2 cells were randomly assigned to four groups:control group (Con, cells were untreated), CoCl2 group (CoCl2, cells were treated with 600μmol/L CoCl2 for 24 h), Sch B pretreat group (CoCl2+Sch B, cells were pretreated with 1μmol/L and 10μmol/L Sch B for 2 h) and Sch B group (Sch B, cells were treated with 1μmol/L and 10μmol/L Sch B for 2 h). CCK-8 kit was used to detect the cell viability of four groups. Flow cytometry was used to detect the apoptotic rate of four groups. The protein expression of hypoxia-inducible factor 1α(HIF-1α) was assessed by Western blot assay. The expressions of HIF-1α and inducible nitric oxide synthase (iNOS) mRNA were determined by RT-PCR. Results Compared with the control group, after treated with 600 μmol/L CoCl2, the cell viability was decreased, and the apoptosis was increased, the expressions of HIF-1α and iNOS mRNA were up-regulated in HK-2 cells. There was no significant difference in the expression of HIF-1α mRNA between control group and CoCl2 group. Compared with the CoCl2 group, after pretreated with 1μmol/L and 10μmol/L Sch B, the cell viability was increased and the apoptosis was decreased, the expressions of HIF-1α and iNOS were down-regulated in HK-2 cells. There were no significant differences in the cell viability and apoptotic rate between control group and Sch B group. Conclusion Pretreatment with Sch B can reduce the apoptosis of HK-2 cells by inhibiting the expression of HIF-1α and iNOS mRNA, which shows protective effects on hypoxia injury.