丹参川穹嗪对尿酸肾损伤模型大鼠FOXO3α表达影响

Effects of Danshen Ligustrazine on Expression of FOXO3α in Rats with Uric Acid Induced Renal Injury

目的探讨丹参川穹嗪对尿酸性肾病大鼠肾脏损伤的保护作用及作用机制。方法设对照组,模型组,丹参川穹嗪低、中、高剂量组(10、20、40mg/kg)和别嘌呤醇(5mg/kg)阳性药物组。干预6周后采用逆转录聚合酶链反应(RT-PCR),蛋白免疫印迹(Western blot),酶联免疫吸附试验(ELISA)检测大鼠肾组织或血清中FOXO3α、TLR4、NLRP3和MCP-1的mRNA和蛋白水平。结果模型组FOXO3αmRNA和蛋白水平低于正常组,而TLR4,NLRP3和MCP-1高于正常组(P<0.05)。模型组FOXO3α的m RNA和蛋白水平低于丹参川芎嗪组和别嘌醇组,而TLR4,NLRP3和MCP-1高于丹参川芎嗪组和别嘌呤醇组(P<0.05)。结论丹参川穹嗪可上调FOXO3α的表达,抑制TLR4,NLRP3和MCP-1的表达,这可能是丹参川穹嗪改善高尿酸血症介导的免疫炎症肾损伤的分子机制。

Objective To explore the protective effect and mechanism of Danshen Ligustrazine on renal injury in rats with uric acid nephropathy. Methods Rats were divided into six groups including normal, model, Danshen Ligustrazine（10、20、40 mg/kg）, and allopurinol（5 mg/kg） positive medicine groups. Six weeks after the intervention, FOXO3α, TLR4, NLRP3 and MCP-1 in rat kidney or serum were analyzed by reverse-transcription polymerase chain reaction（RT-PCR）, Western blot, and enzyme-linked immunosorbent assay（ELISA）. Results The mRNA and protein levels of FOXO3α in model group was lower than the normal group,while the TLR4, NLRP3 and MCP-1 were higher than the normal group（P〈0.05）. The mRNA and protein levels of FOXO3α in model group was lower than the Danshen Ligustrazine group and allopurinol group,while TLR4, NLRP3 and MCP-1 were higher than the Danshen Ligustrazine group and allopurinol group（P〈0.05）. The difference was statistically significant. Conclusion These findings suggest that Danshen Ligustrazine can up-regulate the expression of FOXO3α and inhibit the expression of TLR4, NLRP3 and MCP-1, which may be the biological mechanism of Danshen Ligustrazine recovering hyperuricemia-induced immune inflammatory renal injury.