Tetrandrine attenuates ischemia-reperfusion-induced acute kidney inju-ry in mice through inhibiting inflammatory activation of macrophages mediated by Mincle/Syk signaling pathway
AIM:To investigate the protective effect of tetrandrine(Tet)on mice with ischemia-reperfusion-induced acute kidney injury(IRI-AKI).METHODS:Eight-week-old male C57BL/6 mice were randomly divided into sham group,IRI-AKI group,low-dose(20 mg/kg)Tet group,high-dose(40 mg/kg)Tet group,and quercetin(Que;50 mg/kg)group,each containing six animals.The IRI-AKI model was induced by occluding bilateral renal blood supply for 45 min followed by reperfusion for 3 d.The mice in Tet and Que groups were intraperitoneally treated with corresponding doses of Tet and Que 1 h before surgery and once daily for 3 consecutive days after surgery.The mice in the sham and IRI-AKI groups received an equivalent volume of saline.At the end of the experiment,the animals were sacrificed,and serum and kidney tissues were collected for analysis of renal function,histology,and mRNA and protein expression.In vitro,the anti-inflammatory activity of Tet(1,2 and 4 mg/L)was studied using lipopolysaccharide(LPS;300 μg/L)-stimulated pri-mary mouse bone marrow-derived macrophages(BMDM).RESULTS:(1)Both low and high doses of Tet significantly reduced serum creatinine and blood urea nitrogen levels compared with the IRI-AKI model mice,accompanied by attenuated structural injury of the renal tubules(P<0.05).(2)Treatment with Tet significantly reduced the mRNA and protein levels of interleukin-1β(IL-1β)and IL-6,and the activation of NF-κB signaling pathway,with reduced infiltration of macro-phages after IRI-AKI(P<0.05).(3)In LPS-stimulated BMDM,Tet also inhibited the mRNA and protein expression of IL-1β and IL-6,and the activation of NF-κB signaling(P<0.05).(4)Further experiments showed that Tet significantly reduced the expression of Mincle,Syk and p-Syk in LPS-stimulated BMDM and IRI-AKI mouse kidney tissues(P<0.05).CONCLUSION:Tetrandrine significantly attenuates renal injury in IRI-AKI mice with reduced renal inflammation.The underlying mechanism might be the inhibition of pro-inflammatory Mincle/Syk/NF-κB signaling pathway in macrophages.
国家科技期刊平台
NSTL
万方数据
维普
