Yan Xin1, Gang Li2, Hongxiu Liu2, Dengbin Ai1. 1. Department of Anesthesia, Qingdao Municipal Hospital Qingdao, Shandong, China. 2. Department of Anesthesia, People's Hospital of Rizhao Rizhao, Shandong, China.
Abstract
OBJECTIVE: To determine and explore the effect of Astragalus saponin IV (AS-IV) on ischemia/reperfusion (IR)-induced renal injury and its mechanisms. METHODS: Experimental model of renal I/R was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 6 h. Rats were divided into three groups: ① sham ② IRI ③ IRI/AS-IV. In IRI/AS-IV groups, AS-IV was orally administered once a day to rats at 2 mg·kg(-1)·d(-1) for 7 days prior to ischemia. At 6 h after reperfusion, the inflammatory cytokines and renal function was assessed and NF-κB activity and PUMA expression was detected. Apoptotic cells was detected by TUNEL assay. RESULTS: AS-IV significantly decreased serum and tissue levels of IL-6 and TNF-α, and reduced apoptotic cell counts and histological damage. AS-IV down-regulated the phosphorylation of p65 subunit of NF-κB (NF-κB p65) and PUMA expression, and the NF-κB activity compared to the I/R groups. CONCLUSIONS: AS-IV provided protection against IRI-induced renal injury by reducing apoptosis and inflammation through inhibition of NF-κB activity and PUMA expression. AS-IV pre-treatment ameliorated tubular damage and suppressed the NF-κB p65 expression.
OBJECTIVE: To determine and explore the effect of Astragalus saponin IV (AS-IV) on ischemia/reperfusion (IR)-induced renal injury and its mechanisms. METHODS: Experimental model of renal I/R was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 6 h. Rats were divided into three groups: ① sham ② IRI ③ IRI/AS-IV. In IRI/AS-IV groups, AS-IV was orally administered once a day to rats at 2 mg·kg(-1)·d(-1) for 7 days prior to ischemia. At 6 h after reperfusion, the inflammatory cytokines and renal function was assessed and NF-κB activity and PUMA expression was detected. Apoptotic cells was detected by TUNEL assay. RESULTS: AS-IV significantly decreased serum and tissue levels of IL-6 and TNF-α, and reduced apoptotic cell counts and histological damage. AS-IV down-regulated the phosphorylation of p65 subunit of NF-κB (NF-κB p65) and PUMA expression, and the NF-κB activity compared to the I/R groups. CONCLUSIONS: AS-IV provided protection against IRI-induced renal injury by reducing apoptosis and inflammation through inhibition of NF-κB activity and PUMA expression. AS-IV pre-treatment ameliorated tubular damage and suppressed the NF-κB p65 expression.
Entities:
Keywords:
Kidney; NF-κB; apoptosis; astragaloside IV (AS-IV); inflammatory genes; ischemia reperfusion injury (IRI); p53 upregulated modulator of apoptosis (PUMA)
Authors: M A Daemen; C van 't Veer; G Denecker; V H Heemskerk; T G Wolfs; M Clauss; P Vandenabeele; W A Buurman Journal: J Clin Invest Date: 1999-09 Impact factor: 14.808