蛇床子素对大鼠肾缺血再灌注损伤的影响

Effects of Osthole on Renal Ischemia-reperfusion Injury in Rats

目的探讨蛇床子素对大鼠肾缺血再灌注损伤、炎性因子水平、TLR4信号通路的影响.方法构建肾缺血再灌注大鼠模型并给予蛇床子素干预,观察血流恢复24 h后肾功能变化,HE染色、TUNEL法、ELISA法、流式细胞法和蛋白免疫印迹法分别检测肾组织病理、凋亡、炎性因子和TLR4信号通路蛋白水平.结果蛇床子素(20、40 mg/kg)可降低肾缺血再灌注大鼠尿蛋白、血肌酐、尿素氮水平,改善肾损伤,降低肾凋亡率和TNF-α、iNOS、IL-17、CD4^(+)IL17^(+)水平,提高IL-10和CD4^(+)IL-10^(+)含量,降低肾组织p-TLR-4/TLR-4、p-MyD88/MyD88、p-NF-κB p65/NF-κB p65水平.结论适宜浓度蛇床子素可改善肾缺血再灌注损伤和炎性反应,可能与TLR4信号通路的抑制有关.

Objective To explore the effects of osthole on renal ischemia-reperfusion injury(IRI),levels of inflammatory factors and TLR4 signaling pathway in rats.Methods The rat models of renal ischemia-reperfusion were constructed and intervened with osthole.The changes of renal function at 24 h after blood flow recovery were observed.The pathological changes of renal tissues,apoptosis,levels of inflammatory factors and TLR4 signaling pathway proteins were detected by HE staining,TUNEL,EUSA,flow cytometry and Western blotting.Results Osthole(20,40 mg/kg)could reduce levels of urine protein,serum creatinine and blood urea nitrogen in rats with renal ischemia-reperfusion,improve renal injury,reduce renal apoptosis rate and levels of TNF-a,iNOS,IL-17 and CD4^(+)IL17^(+),increase contents of IL-10 and CD4^(+)IL-10^(+),and reduce levels of p-TLR-4/TLR-4,p-MyD88/MyD88 and p-NF-KB/p65/NF-KB p65 in renal tissues.Conclusion Optimal concentration of osthole can improve renal IRI and inflammation response,which may be related to inhibiting TLR4 signaling pathway.