期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 120, 期 3, 页码 4291-4300出版社
WILEY
DOI: 10.1002/jcb.27714
关键词
artemisinin (Art); NF-kappa B/NLRP3; tubulointerstitial inflammation
资金
- Key Project of the National Natural Scientific Foundation [81670696, 81720108007]
- Clinic Research Center of Jiangsu Province [BL2014080]
Artemisinin (Art) is isolated from Artemisia annua L. and known as the most effective antimalaria drugs. Previous studies demonstrated that it could exert an immune-regulatory effect on autoimmune diseases. In this study, we first investigated its potential role in tubulointerstitial inflammation and fibrosis in rats with 5/6 nephrectomy. Subtotal nephrectomized (SNx) rats were orally administered Art (100 mg center dot kg(-1)center dot d(-)1) for 16 weeks. Blood and urine samples were collected for biochemical examination. Kidney tissues were collected for immunohistochemistry and Western blot analyses. Ang II-induced injury of the human kidney 2 (HK-2) cells was used for in vitro study. It was shown that Art could significantly attenuate the renal function decline in SNx rats compared with control. More importantly, Art treatment significantly reduced the tubulointerstitial inflammation and fibrosis, as demonstrated by the evaluation of renal pathology. Furthermore, Art inhibited the activation of NLRP3 inflammasome and NF-kappa B in the kidneys. In in vitro study, Art pretreatment could significantly prevent the activation of NLRP3 inflammasome and NF-kappa B in Ang II-treated HK-2 cells, while BAY11-7082 (an inhibitor of NF-kappa B) significantly inhibited Ang II-induced NLRP3 inflammasome activation. This study suggested that Art could provide renoprotective role by attenuating the tubulointerstitial inflammation and fibrosis in SNx rats by downregulating the NF-kappa B/NLRP3 signaling pathway.
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