2021 年 67 巻 1 号 p. 39-45
Objective: Stroke is associated with high risks for mortality. The bidirectional communication between ischemic brain and other organ dysfunctions is widely recognized. However, the mechanisms underlying cerebrorenal crosstalk remains unclear. Herein, we investigated the effect of ischemic stroke on the kidney using a middle cerebral artery occlusion (MCAO) model. Moreover, we explored the effects of overexpression of liver-type fatty acid binding protein (L-FABP), as antioxidant role in this disease.
Methods: MCAO was performed in wild-type (WT) and L-FABP transgenic (Tg) mice. At 24 h after this procedure, renal hypoxia, oxidative stress, and lipid metabolism were examined. Hypoxia was examined by pimonidazole staining and oxidative stress was examined by heme oxygenase-1 staining in MCAO WT mice. The biomarkers such as urinary 8-OHdG for oxidative stress and silent information regulator 2 mammalian homolog 1, peroxisome proliferator-activated receptor α, and 3-hydroxy-3-methylglutaryl-CoA reductase for renal lipid metabolism were compared between MCAO WT and Tg mice.
Results: MCAO enhanced renal hypoxia and oxidative stress, and the biomarkers for oxidative stress tended to increase in the MCAO WT mice than in the sham-operated control mice, and these were diminished by L-FABP overexpression. The expression levels of renal lipid metabolism-related genes markedly changed. These alterations were blocked in the L-FABP Tg mice.
Conclusions: Ischemic stroke-mediated renal oxidative stress and the resulting alteration of lipid metabolism could partly account for cerebrorenal connection and the induction of renal L-FABP activity and could be a novel therapeutic target for the prevention of renal diseases in patients with stroke.
