有哪些信誉好的足球投注网站amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat急性肾损伤的改善lipopolysaccharide-induced全身炎症反应综合征的醛糖还原酶抑制剂,fidarestat.pdfVIP
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amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat急性肾损伤的改善lipopolysaccharide-induced全身炎症反应综合征的醛糖还原酶抑制剂,fidarestat
Amelioration of Acute Kidney Injury in
Lipopolysaccharide-Induced Systemic Inflammatory
Response Syndrome by an Aldose Reductase Inhibitor,
Fidarestat
1 1 1 1 2 2
Kazunori Takahashi , Hiroki Mizukami , Kosuke Kamata , Wataru Inaba , Noriaki Kato , Chihiro Hibi ,
Soroku Yagihashi1*
1 Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan, 2 Sanwa Kagaku Kenkyusho, Nagoya, Japan
Abstract
Background: Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney
injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty
for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced
cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism.
Methods: Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection
were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines
(interleukin-1b, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-a) and their mRNA expressions in
the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney.
Results: Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before
(29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea
nitrogen, creatinine and cytokines, and AR inhibitor treatment suppress
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