The effect of store-operated calcium entry inhibitor on liver and kidney injury induced by paraquat / 中华急诊医学杂志

ABSTRACT

Objective:To investigate the effect of SKF96365, store-operated calcium entry (SOCE) inhibitor, on liver and kidney injury induced by paraquat (PQ).Methods:A549 cells were cultured in vitro and divided into the control group (DMSO group, SKF 2 μmol/L group, and SKF 10 μmol/L group) and PQ group (PQ+DMSO group, PQ+SKF 2 μmol/L group, and PQ+SKF 10 μmol/L group). The nuclear factor of activated T cells (NFAT) in A549 cells was detected by luciferase reporter gene technique. The mouse model of PQ poisoning was constructed and divided into the control group, SKF group, PQ group and PQ+SKF group. In the PQ group, mice were injected with 50 mg/kg PQ intraperitoneally; in the SKF group, mice were injected intraperitoneally with 10 mg/kg SKF96365 for 3 days. Mice in the PQ+SKF group received 50 mg/kg intraperitoneal injection of PQ once and 10 mg/kg intraperitoneal injection of SKF96365 daily for 3 days. On the fourth day, the mice were sacrificed, and the liver and kidney tissues were taken. The histopathological changes of liver and kidney tissues were observed by hematoxylin-eosin (H&E) staining, and the apoptosis of liver and kidney tissues was observed by TUNEL staining. One-way analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between groups were performed using the least significant difference t-test. Results:The luciferase reporter gene technology showed that NFAT was significantly activated in the PQ group. After pretreatment with SKF96365, NFAT activation decreased sharply in a dose-dependent manner. HE staining showed that the outline structure of liver and kidney tissues in the PQ groups were unclear, cells swelled and a large number of inflammatory cells infiltrated; in the PQ+SKF group, liver cell swelling and inflammatory cell infiltration decreased significantly. TUNEL staining showed that the apoptotic cells in liver and kidney tissues increased in the PQ groups, and the apoptosis decreased remarkably in the PQ+SKF group.Conclusions:SOCE inhibitor SKF96365 can significantly reduce the liver and kidney injury caused by PQ.