ISSN 1006-298X      CN 32-1425/R

Chinese Journal of Nephrology, Dialysis & Transplantation ›› 2021, Vol. 30 ›› Issue (3): 239-245.DOI: 10.3969/j.issn.1006298X.2021.03.009

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Experimental study of receptor interaction protein kinase 1 inhibitor (necrostatin-1) in treatment of lupus nephritis

  

  • Online:2021-06-28 Published:2021-06-22

Abstract:

Objective:To explore the mechanism of necroptosis in lupus nephritis and the efficacy of receptor interaction protein kinase 1 (RIPK1) inhibitor necrostatin1(Nec1) in the treatment of lupus nephritis.
Methodology:MRL/lpr mice at the age of 19 weeks was injected intraperitoneally with Nec1 [35 mg/(kg·d)] for 3 weeks. Changes were detected in serum creatinine, complement levels and urine protein/creatinine ratio. Kidney pathological staining was used to observe kidney pathological changes and the changes in expression of necroptosisrelated proteins. In vitro,the expression of necroptosisrelated molecules in mesangial cells treated with Nec1 were measured. Changes in the expression of proinflammatory factors were detected by qRTPCR.
Results:The systemic immune inflammatory response and kidney damage of mice with lupus nephritis were alleviated after treatment with Nec1,serum antinuclear antibodies titers,antidoublestranded DNA antibody titers,and urine protein/creatinine ratio were decreased,and Nec1 inhibited mesangial cell necrosis and the release of proinflammatory factors in vitro.
Conclusion:RIPK1 inhibitor Nec1 can inhibit the necrotizing apoptosis of mesangial cells and relieve the symptoms of lupus nephritis.


Key words: lupus nephritis, necroptosis, necrostatin-1, mesangial cell